[Occult hepatitis B virus infection in normal population, Xiamen].

PubMed

He, Shuizhen; Su, Chenghao; Shen, Litong; Niu, Jianjun

2015-02-01

To investigate the prevalence of occult HBV infection in the normal population in Xiamen. 4 437 registered permanent residents, aged 1-59 years old, were selected in Xiamen using stratified random sampling method from September to October in 2006. Serum samples were obtained, the basic characteristics, inoculation of HBV vaccine, and liver disease were surveyed. The serum samples were tested five HBV seroimmunological markers. The HBsAg-negative specimens were subjected to HBV-DNA detection by nested PCR targeting for multiple gene segments. The amplified products were sequenced and the sequence was used for determination of HBV genotype and mutation analysis of amino acids located in HBsAg "a" epitope. Subjects with serum detectable HBV-DNA and negative result of HBsAg were considered as occult HBV infection. Among the 4 437 subjects, 482 individuals were observed HBsAg positive and 3 944 were observed negative. Of the 3 955 HBsAg- negative specimens, 27 occult HBV infections were determined with the positive rate of 0.68% (27/3 955). There were 16 samples with genotype B and 11 with genotype C. 3 types of amino acid (AA) mutation (M133T, T140I, G145R) that influence "a" epitope conformation were observed in 9 subjects with occult HBV infection. S region was successfully sequenced in 312 of the 482 HBsAg positive samples. In subjects with occult HBV infection, the infection rate of genotype C HBV (40.74%, 11/27), inoculation rate of HBV vaccine (62.96%, 17/27), positive rate of HBsAb (51.85%, 14/27), and mutation rate of critical amino acid of "a" epitope (33.33%, 9/27) were higher than HBsAg positive individuals (22.76% (71/312), 13.78% (43/312),0.32% (1/312),0.99% (31/312), respectively), and all the difference were significant (χ(2) = 4.29, 41.26, 156.00, 13.07, respectively, and P value = 0.038, <0.001, <0.001, <0.001, respectively). While the average age in subjects with occult HBV infection (18.3 ± 16.2) were lower than that in HBsAg positive infection (34.4 ± 11.6), and the difference was significant (t = 6.67, P < 0.001). The reactive rate of HBeAb (11.11%, 3/27) and HBcAb (62.96%, 17/27) in subjects with occult HBV infection were lower than that in HBsAg positive infection (74.36% (232/312), 98.40% (307/312)), and the difference were significant (χ(2) = 46.74, 73.78, respectively, and P value <0.001, <0.001, respectively). In normal population in Xiamen, the infection rate of genotype C, the positive rate of HBsAb, the HBV vaccination rate, and the key AA mutation rate in "a" epitope are significantly higher in occult HBV infection than in HBsAg positive infection, and the age, the positive rate of HBeAb and HBcAb are significantly lower.

Fibronectin gene polymorphism in patients with lung cancer.

PubMed

Siemianowicz, K; Gminski, J; Francuz, T; Syzdol, M; Polanska, D; Machalski, M; Brulinski, K; Magiera-Molendowska, H

2001-01-01

Fibronectin (FN) is a glycoprotein component of connective tissue. It is involved in cancer progression. FN plays a role in non-neoplasmatic lung pathology in which fibronectin gene polymorphisms (RFLPs) have been studied. The aim of our work was to evaluate the frequency of two of fibronectin RFLPs: genotypes AB, AA, BB (HaeIII) and CD, CC, DD (MspI) in patients with lung cancer. The studied group consisted of 63 patients with squamous cell lung cancer and 53 controls without any malignant or proliferative disease. There were no statistically significant differences in the distribution of studied genotypes between lung cancer patients and controls.

Restriction fragment length polymorphism of the human c-fms gene.

PubMed Central

Xu, D Q; Guilhot, S; Galibert, F

1985-01-01

By using blot hybridization with a v-fms probe, a polymorphism for EcoRI, HindIII, and BamHI restriction endonuclease sites associated with the human c-fms locus was observed in a random adult population. This restriction fragment length polymorphism can be explained on the basis of the existence of two alleles, a and b, and is due to a short (congruent to 500 base pairs) deletion characteristic of allele a. The distribution in the analyzed population (48 unrelated individuals) is 23% heterozygotes ab, 75% homozygotes bb, and 2% homozygotes aa. Though the inheritance of this polymorphism follows a Mendelian pattern, the children from couples ab X bb are of the following genotype: 74% ab and 26% bb. These deviations from the expected frequencies of 50% suggest a selective pressure in favor of heterozygotes. Images PMID:2986142

Binary Star Orbits. 3. Revisiting the Remarkable Case of Tweedledum and Tweedledee

DTIC Science & Technology

2010-06-11

Observation Date 0.00 0.05 0.10 0.15 0.20 S ep ar at io n D iff er en ce FIN 332 Aa,Ab Unresolved Aa,Ab bB,aBdevlosernU bB,aB 233 NIF 1960 1970 1980 1990...2000 2010 Observation Date 0 50 100 150 200 P os iti on A ng le D iff er en ce FIN 332 Aa,Ab Unresolved Aa,Ab bB,aBdevlosernU bB,aB 233 NIF Figure

A novel single nucleotide polymorphism in exon 7 of LPL gene and its association with carcass traits and visceral fat deposition in yak (Bos grunniens) steers.

PubMed

Ding, X Z; Liang, C N; Guo, X; Xing, C F; Bao, P J; Chu, M; Pei, J; Zhu, X S; Yan, P

2012-01-01

Lipoprotein lipase (LPL) is considered as a key enzyme in the lipid deposition and metabolism in tissues. It is assumed to be a major candidate gene for genetic markers in lipid deposition. Therefore, the polymorphisms of the LPL gene and associations with carcass traits and viscera fat content were examined in 398 individuals from five yak (Bos grunniens) breeds using PCR-SSCP analysis and DNA sequencing. A novel nucleotide polymorphism (SNP)-C→T (nt19913) was identified located in exon 7 in the coding region of the LPL gene, which replacement was responsible for a Phe-to-Ser substitution at amino acid. Two alleles (A and B) and three genotypes designed as AA, AB and BB were detected in the PCR products. The frequencies of allele A were 0.7928, 0.7421, 0.7357, 0.6900 and 0.7083 for Tianzhu white yak (WY), Gannan yak (GY), Qinghai-Plateau yak (PY), Xinjiang yak (XY) and Datong yak (DY), respectively. The SNP loci was in Hardy-Weinberg equilibrium in five yak populations (P>0.05). Polymorphism of LPL gene was shown to be associated with carcass traits and lipid deposition. Least squares analysis revealed that there was a significant effect on live-weight (LW) (P<0.01), average daily weight gain (ADG) and carcass weight (P<0.05). Individuals with genotype BB had lower mean values than those with genotype AA and AB for loin eye area and viscera fat weight (% of LW) in 25-36 months (P<0.05). The results indicated that LPL gene is a strong candidate gene that affects carcass traits and fat deposition in yak.

Correlation of the A-FABP Gene Polymorphism and mRNA Expression with Intramuscular Fat Content in Three-Yellow Chicken and Hetian-Black Chicken.

PubMed

Wang, Yong; Chen, Hongwei; Han, Diangang; Chen, Ying; Muhatai, Gemingguli; Kurban, Tursunjan; Xing, Jinming; He, Jianzhong

2017-01-02

The adipocyte-type fatty acid-binding protein (A-FABP) is considered a candidate gene for fat metabolism; thus, it affects fat deposition in chickens. The present study was designed to examine the polymorphism and mRNA abundance of the A-FABP gene with intramuscular fat (IMF) in the pectoralis muscles (PM) and leg muscles (LM) of Three-yellow Chicken (TYC) and Hetian-black Chicken (HTBC). In total, 60 TYCs and 60 HTBCs were sacrificed using exsanguination at market age. The IMF contents of the PM and LM in the HTBC were significantly higher than those in the TYC. Three genotypes of the A-FABP gene first exon, AA, AB, and BB, were examined by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), and a C51 T mutational site, which is a silent substitution mutation, was revealed. The IMF contents of the AA genotype in the PM of the HTBC were significantly higher than those in the AB genotype; thus, the C51 T mutable site is a gene marker for selecting a higher IMF content in the PM of the HTBC. The relative expression of the A-FABP mRNA in the LM of the HTBC, which was measured by quantitative real-time PCR, was significantly higher than in the TYC. A significantly positive association was detected between A-FABP expression with the IMF contents of the PM and LM of both the TYC and the HTBC. These results provide basic data that might be helpful to further research the role of the A-FABP gene in fat deposition and fatty acid metabolism in chickens.

A polymorphism in the insulin-like growth factor 1 gene is associated with postpartum resumption of ovarian cyclicity in Holstein-Friesian cows under grazing conditions

PubMed Central

2013-01-01

Background Insulin-like growth factor 1 (IGF-1) gene is considered as a promising candidate for the identification of polymorphisms affecting cattle performance. The objectives of the current study were to determine the association of the single nucleotide polymorphism (SNP) IGF-1/SnaBI with fertility, milk production and body condition traits in Holstein-Friesian dairy cows under grazing conditions. Methods Seventy multiparous cows from a commercial herd were genotyped for the SNP IGF-1/SnaBI. Fertility measures evaluated were: interval to commencement of luteal activity (CLA), calving to first service (CFS) and calving to conception (CC) intervals. Milk production and body condition score were also evaluated. The study period extended from 3 wk before calving to the fourth month of lactation. Results and discussion Frequencies of the SNP IGF-1/SnaBI alleles A and B were 0.59 and 0.41, respectively. Genotype frequencies were 0.31, 0.54 and 0.14 for AA, AB and BB, respectively. Cows with the AA genotype presented an early CLA and were more likely to resume ovarian cyclicity in the early postpartum than AB and BB ones. No effect of the SNP IGF-1/SnaBI genotype was evidenced on body condition change over the experimental period, suggesting that energy balance is not responsible for the outcome of postpartum ovarian resumption in this study. Traditional fertility measures were not affected by the SNP IGF-1/SnaBI. Conclusion To our knowledge this is the first report describing an association of the SNP IGF-1/SnaBI with an endocrine fertility measure like CLA in cattle. Results herein remark the important role of the IGF-1gene in the fertility of dairy cows on early lactation and make the SNP IGF-1/SnaBI an interesting candidate marker for genetic improvement of fertility in dairy cattle. PMID:23409757

Autoantibodies to human tryptophan hydroxylase and aromatic L-amino acid decarboxylase.

PubMed

Dal Pra, Chiara; Chen, Shu; Betterle, Corrado; Zanchetta, Renato; McGrath, Vivienne; Furmaniak, Jadwiga; Rees Smith, Bernard

2004-03-01

To assess the prevalence of autoantibodies (Abs) to tryptophan hydroxylase (TPH) and aromatic l-amino acid decarboxylase (AADC) in patients with different autoimmune diseases and to analyse their respective epitopes. TPH and AADC Abs were measured in an immunoprecipitation assay using (35)S-labelled full-length and fragments of TPH and AADC. Patients with different autoimmune adrenal diseases (n=84), non-adrenal autoimmune diseases (n=37), idiopathic vitiligo (n=8) and 56 healthy blood donors were studied. Fourteen of twenty-three (61%) of patients with autoimmune polyglandular syndrome (APS) type I and 1/34 (3%) of patients with isolated Addison's disease (AD) were positive for TPH Abs. None of the patients with APS type II (n=27), coeliac disease (n=10), autoimmune thyroid disease (AITD) (n=11), type 1 diabetes mellitus (DM) (n=16) or idiopathic vitiligo (n=8) was positive for TPH Abs. AADC Abs were detected in 12/23 (52%) patients with APS type I, in 1/29 (3%) patients with APS type II and 1/34 (3%) patients with isolated AD. None of the patients with coeliac disease, type 1 DM, AITD or idiopathic vitiligo was positive for AADC Abs. TPH Abs were found to interact with the C-terminal amino acids (aa) 308-423, central aa 164-205 and N-terminal aa 1-105 of the TPH molecule. AADC Ab binding epitopes were within the C-terminal aa 382-483, the central aa 243-381 and the N-terminal aa 1-167. Our study suggests that TPH Abs and AADC Abs react with several different epitopes and that different epitopes are recognized by different sera. The prevalence of TPH Abs and AADC Abs in patients with APS type I in our study is in agreement with previous reports. TPH Abs and AADC Abs were found very rarely in patients with other forms of autoimmune adrenal disease and were not detected in patients with non-adrenal autoimmune diseases.

Stacking stability of MoS2 bilayer: An ab initio study

NASA Astrophysics Data System (ADS)

Tao, Peng; Guo, Huai-Hong; Yang, Teng; Zhang, Zhi-Dong

2014-10-01

The study of the stacking stability of bilayer MoS2 is essential since a bilayer has exhibited advantages over single layer MoS2 in many aspects for nanoelectronic applications. We explored the relative stability, optimal sliding path between different stacking orders of bilayer MoS2, and (especially) the effect of inter-layer stress, by combining first-principles density functional total energy calculations and the climbing-image nudge-elastic-band (CI-NEB) method. Among five typical stacking orders, which can be categorized into two kinds (I: AA, AB and II: AA', AB', A'B), we found that stacking orders with Mo and S superposing from both layers, such as AA' and AB, is more stable than the others. With smaller computational efforts than potential energy profile searching, we can study the effect of inter-layer stress on the stacking stability. Under isobaric condition, the sliding barrier increases by a few eV/(ucGPa) from AA' to AB', compared to 0.1 eV/(ucGPa) from AB to [AB]. Moreover, we found that interlayer compressive stress can help enhance the transport properties of AA'. This study can help understand why inter-layer stress by dielectric gating materials can be an effective means to improving MoS2 on nanoelectronic applications.

Mannose-Binding Lectin Codon 54 Gene Polymorphism and Vulvovaginal Candidiasis: A Systematic Review and Meta-Analysis

PubMed Central

Nedovic, Bojan; Posteraro, Brunella; Leoncini, Emanuele; Amore, Rosarita; Sanguinetti, Maurizio; Boccia, Stefania

2014-01-01

Mannose-binding lectin (MBL) plays a key role in the human innate immune response. It has been shown that polymorphisms in the MBL2 gene, particularly at codon 54 (variant allele B; wild-type allele designated as A), impact upon host susceptibility to Candida infection. This systematic review and meta-analysis were performed to assess the association between MBL2 codon 54 genotype and vulvovaginal candidiasis (VVC) or recurrent VVC (RVVC). Studies were searched in MEDLINE, SCOPUS, and ISI Web of Science until April 2013. Five studies including 704 women (386 cases and 318 controls) were part of the meta-analysis, and pooled ORs were calculated using the random effects model. For subjects with RVVC, ORs of AB versus AA and of BB versus AA were 4.84 (95% CI 2.10–11.15; P for heterogeneity = 0.013; I 2 = 68.6%) and 12.68 (95% CI 3.74–42.92; P for heterogeneity = 0.932, I 2 = 0.0%), respectively. For subjects with VVC, OR of AB versus AA was 2.57 (95% CI 1.29–5.12; P for heterogeneity = 0.897; I 2 = 0.0%). This analysis indicates that heterozygosity for the MBL2 allele B increases significantly the risk for both diseases, suggesting that MBL may influence the women's innate immunity in response to Candida. PMID:25143944

PON1-192 phenotype and genotype assessments in 918 subjects of the Stanislas cohort study.

PubMed

Vincent-Viry, Monique; Sass, Catherine; Bastien, Sabine; Aguillon, Dominique; Siest, Gérard; Visvikis, Sophie

2003-04-01

This study describes the factors of variation of the enzymes related to the PON1-192 phenotype assessment, i.e., basal paraoxonase, salt-stimulated paraoxonase and arylesterase activities, and compares the PON1-192 phenotype to the PON1-192 genotype assessments in supposedly healthy subjects issued from the Stanislas cohort study. The studied population included 918 subjects, i.e., 221 families including 441 adults and 477 children aged 4 to 58 years. Potential determinants such as age, gender, body mass index, alcohol and tobacco consumption, and oral contraceptive intake have been studied. The PON ratio (salt-stimulated paraoxonase/arylesterase) was trimodally distributed and the cut-off values used to differentiate the two homozygous (AA and BB phenotypes) from the heterozygous (AB phenotype) subjects were 3.0 and 7.0 in this study. In males, basal paraoxonase and salt-stimulated paraoxonase activities were not affected by alcohol consumption and current smoking, but basal paraoxonase activity was decreased by 15% by current smoking and was increased by 15% by oral contraceptive intake in females as was the salt-stimulated paraoxonase activity. The level of discordance between phenotype and genotype assessments was 7.2% (66/918). Most of the discrepancies were observed between the BB and AB phenotypes (4.25%).

Mitochondrial DNA analyses reveal low genetic diversity in Culex quinquefasciatus from residential areas in Malaysia.

PubMed

Low, V L; Lim, P E; Chen, C D; Lim, Y A L; Tan, T K; Norma-Rashid, Y; Lee, H L; Sofian-Azirun, M

2014-06-01

The present study explored the intraspecific genetic diversity, dispersal patterns and phylogeographic relationships of Culex quinquefasciatus Say (Diptera: Culicidae) in Malaysia using reference data available in GenBank in order to reveal this species' phylogenetic relationships. A statistical parsimony network of 70 taxa aligned as 624 characters of the cytochrome c oxidase subunit I (COI) gene and 685 characters of the cytochrome c oxidase subunit II (COII) gene revealed three haplotypes (A1-A3) and four haplotypes (B1-B4), respectively. The concatenated sequences of both COI and COII genes with a total of 1309 characters revealed seven haplotypes (AB1-AB7). Analysis using tcs indicated that haplotype AB1 was the common ancestor and the most widespread haplotype in Malaysia. The genetic distance based on concatenated sequences of both COI and COII genes ranged from 0.00076 to 0.00229. Sequence alignment of Cx. quinquefasciatus from Malaysia and other countries revealed four haplotypes (AA1-AA4) by the COI gene and nine haplotypes (BB1-BB9) by the COII gene. Phylogenetic analyses demonstrated that Malaysian Cx. quinquefasciatus share the same genetic lineage as East African and Asian Cx. quinquefasciatus. This study has inferred the genetic lineages, dispersal patterns and hypothetical ancestral genotypes of Cx. quinquefasciatus. © 2013 The Royal Entomological Society.

ORBITAL AND PHYSICAL PROPERTIES OF THE σ Ori Aa, Ab, B TRIPLE SYSTEM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Simón-Díaz, S.; Caballero, J. A.; Apellániz, J. Maíz

2015-02-01

We provide a complete characterization of the astrophysical properties of the σ Ori Aa, Ab, B hierarchical triple system and an improved set of orbital parameters for the highly eccentric σ Ori Aa, Ab spectroscopic binary. We compiled a spectroscopic data set comprising 90 high-resolution spectra covering a total time span of 1963 days. We applied the Lehman-Filhés method for a detailed orbital analysis of the radial velocity curves and performed a combined quantitative spectroscopic analysis of the σ Ori Aa, Ab, B system by means of the stellar atmosphere code FASTWIND. We used our own plus other available information onmore » photometry and distance to the system for measuring the radii, luminosities, and spectroscopic masses of the three components. We also inferred evolutionary masses and stellar ages using the Bayesian code BONNSAI. The orbital analysis of the new radial velocity curves led to a very accurate orbital solution of the σ Ori Aa, Ab pair. We provided indirect arguments indicating that σ Ori B is a fast-rotating early B dwarf. The FASTWIND+BONNSAI analysis showed that the Aa, Ab pair contains the hottest and most massive components of the triple system while σ Ori B is a bit cooler and less massive. The derived stellar ages of the inner pair are intriguingly younger than the one widely accepted for the σ Orionis cluster, at 3 ± 1 Ma. The outcome of this study will be of key importance for a precise determination of the distance to the σ Orionis cluster, the interpretation of the strong X-ray emission detected for σ Ori Aa, Ab, B, and the investigation of the formation and evolution of multiple massive stellar systems and substellar objects.« less

Warfarin sensitivity genotyping: a review of the literature and summary of patient experience.

PubMed

Moyer, Thomas P; O'Kane, Dennis J; Baudhuin, Linnea M; Wiley, Carmen L; Fortini, Alexandre; Fisher, Pamela K; Dupras, Denise M; Chaudhry, Rajeev; Thapa, Prabin; Zinsmeister, Alan R; Heit, John A

2009-12-01

The antithrombotic benefits of warfarin are countered by a narrow therapeutic index that contributes to excessive bleeding or cerebrovascular clotting and stroke in some patients. This article reviews the current literature describing warfarin sensitivity genotyping and compares the results of that review to the findings of our study in 189 patients at Mayo Clinic conducted between June 2001 and April 2003. For the review of the literature, we identified relevant peer-reviewed articles by searching the Web of Knowledge using key word warfarin-related adverse event. For the 189 Mayo Clinic patients initiating warfarin therapy to achieve a target international normalized ratio (INR) in the range of 2.0 to 3.5, we analyzed the CYP2C9 (cytochrome P450 2C9) and VKORC1 (vitamin K epoxide reductase complex, subunit 1) genetic loci to study the relationship among the initial warfarin dose, steady-state dose, time to achieve steady-state dose, variations in INR, and allelic variance. Results were compared with those previously reported in the literature for 637 patients. The relationships between allelic variants and warfarin sensitivity found in our study of Mayo Clinic patients are fundamentally the same as in those reported by others. The Mayo Clinic population is predominantly white and shows considerable allelic variability in CYP2C9 and VKORC1. Certain of these alleles are associated with increased sensitivity to warfarin. Polymorphisms in CYP2C9 and VKORC1 have a considerable effect on warfarin dose in white people. A correlation between steady-state warfarin dose and allelic variants of CYP2C9 and VKORC1 has been demonstrated by many previous reports and is reconfirmed in this report. The allelic variants found to most affect warfarin sensitivity are CYP2C9*1*1-VKORC1BB (less warfarin sensitivity than typical); CYP2C9*1*1-VKORC1AA (considerable variance in INR throughout initiation); CYP2C9*1*2-VKORC1AB (more sensitivity to warfarin than typical); CYP2C9*1*3-VKORC1AB (much more sensitivity to warfarin than typical); CYP2C9*1*2-VKORC1AB (much more sensitivity to warfarin than typical); CYP2C9*1*3-VKORC1AA (much more sensitivity to warfarin than typical); and CYP2C9*2*2-VKORC1AB (much more sensitivity to warfarin than typical). Although we were unable to show an association between allelic variants and initial warfarin dose or dose escalation, an association was seen between allelic variant and steady-state warfarin dose. White people show considerable variance in CYP2C9 allele types, whereas people of Asian or African descent infrequently carry CYP2C9 allelic variants. The VKORC1AA allele associated with high warfarin sensitivity predominates in those of Asian descent, whereas white people and those of African descent show diversity, carrying either the VKORC1BB, an allele associated with low warfarin sensitivity, or VKORC1AB or VKORC1AA, alleles associated with moderate and high warfarin sensitivity, respectively.

Nanobeads-based assays. The case of gluten detection

NASA Astrophysics Data System (ADS)

Venditti, Iole; Fratoddi, Ilaria; Vittoria Russo, Maria; Bellucci, Stefano; Crescenzo, Roberta; Iozzino, Luisa; Staiano, Maria; Aurilia, Vincenzo; Varriale, Antonio; Rossi, Mosè; D'Auria, Sabato

2008-11-01

In order to verify if the use of nanobeads of poly[phenylacetylene-(co-acrylic acid)] (PPA/AA) in the ELISA test would affect the immune-activity of the antibodies (Ab) and/or the activity of the enzymes used to label the Ab anti-rabbit IGg, in this work we immobilized the horse liver peroxidase labelled Ab anti-rabbit IGg onto PPA/AA nanobeads. The gluten test was chosen as the model to demonstrate the usefulness of these nanobeads in immunoassays. The synthesis of PPA/AA nanobeads was performed by a modified emulsion polymerization. Self-assembly of nanospheres with mean diameter equal to 200 nm was achieved by casting aqueous suspensions. The materials were characterized by traditional spectroscopic techniques, while the size and dispersion of the particles were analysed by scanning electron microscopy (SEM) measurements. The obtained results show that the immobilization process of the Abs onto PPA/AA did not affect either the immune-response of the Abs or the functional activity of the peroxidase suggesting the usefulness of PPA/AA for the design of advanced nanobeads-based assays for the simultaneous screening of several analytes in complex media.

HST/STIS ULTRAVIOLET SPECTROSCOPY OF THE COMPONENTS OF THE MASSIVE TRIPLE STAR δ ORI A

DOE Office of Scientific and Technical Information (OSTI.GOV)

Richardson, Noel D.; Moffat, Anthony F. J.; Gull, Theodore R.

2015-07-20

The multiple star system of δ Orionis is one of the closest examples of a system containing a luminous O-type, bright giant star (component Aa1). It is often used as a spectral-type standard and has the highest observed X-ray flux of any hot-star binary. The main component Aa1 is orbited by two lower mass stars, faint Aa2 in a 5.7 day eclipsing binary, and Ab, an astrometric companion with an estimated period of 346 years. Generally the flux from all three stars is recorded in ground-based spectroscopy, and the spectral decomposition of the components has proved difficult. Here we presentmore » Hubble Space Telescope/Space Telescope Imaging Spectrograph ultraviolet spectroscopy of δ Ori A that provides us with spatially separated spectra of Aa and Ab for the first time. We measured radial velocities for Aa1 and Ab in two observations made near the velocity extrema of Aa1. We show tentative evidence for the detection of the Aa2 component in cross-correlation functions of the observed and model spectra. We discuss the appearance of the UV spectra of Aa1 and Ab with reference to model spectra. Both stars have similar effective temperatures, but Ab is fainter and is a rapid rotator. The results will help in the interpretation of ground-based spectroscopy and in understanding the physical and evolutionary parameters of these massive stars.« less

Effect of nitrogen fertilisation on the amino acid digestibility of different triticale genotypes in caecectomised laying hens.

PubMed

Siegert, Wolfgang; Boguhn, Jeannette; Maurer, Hans Peter; Weiss, Jochen; Zuber, Tobias; Möhring, Jens; Rodehutscord, Markus

2017-01-01

The influence of nitrogen fertilisation and genotype on the amino acid (AA) digestibility of triticale grain was investigated in caecectomised laying hens. Three genotypes, Grenado, EAW6002 and Lasko, were cultivated with and without nitrogen fertilisation at the end of the heading stage. The six triticale variants as well as a basal diet were each used to feed seven laying hens in a 7 × 7 Latin square design. Nitrogen fertilisation influenced the digestibility of Cys, Glu, Phe and Ser in some triticale genotypes and reduced Ala, Ile, Lys, Met and Val digestibility in all genotypes (P < 0.05). Nitrogen fertilisation increased the concentration of all AAs in the grain. Consequently, the concentration of digestible AAs in the grains was increased for most AAs upon nitrogen fertilisation. Overall, Lys had the lowest digestibility, whereas that of Glu and Pro was the highest. For the triticale genotypes, the level of AA digestibility was highest for EAW6002 followed by Lasko and Grenado, with significant differences (P < 0.05) between genotypes for some but not all AAs. The results indicated that the accuracy of the digestible AA supply for hen feeding might benefit from considering fertilisation and genotype-specific digestibility data in feed formulation. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Genetic association of sequence variation in exon 3 of the swine leukocyte antigen-DQA gene with piglet diarrhea in Large White, Landrace, and Duroc piglets.

PubMed

Yang, Q L; Huang, X Y; Kong, J J; Zhao, S G; Liu, L X; Gun, S B

2016-08-19

Piglet diarrhea is one of the primary factors that affects the benefits of the swine industry. Recent studies have shown that exon 2 of the swine leukocyte antigen-DQA gene is associated with piglet resistance to diarrhea; however, the contributions of additional exon coding regions of this gene remain unclear. Here, we detected and sequenced variants in the exon 3 region and examined their associations with diarrhea infection in 425 suckling piglets using the polymerase chain reaction-single-strand conformational polymorphism and sequencing analysis. The results revealed that exon 3 of the swine leukocyte antigen-DQA gene is highly polymorphic and pivotal to both diarrhea susceptibility and resistance in piglets. We identified 14 genotypes (AA, AB, BB, BC, CC, EE, EF, BE, BF, CF, DD, DH, GG, and GF) and eight alleles (A-H) that were generated by 14 nucleotide variants, eight of which were novel, and three nucleotide deletions. Statistical analyses revealed that the genotypes AB and EF were associated with resistance to diarrheal disease (P < 0.05), and the genotype DD may contribute to diarrhea susceptibility but was unique to Large White pigs (P > 0.05). These results elucidate the genetic and immunological background to piglet diarrhea, and provide useful information for resistance breeding programs.

MCT1 A1470T: a novel polymorphism for sprint performance?

PubMed

Sawczuk, Marek; Banting, Lauren K; Cięszczyk, Paweł; Maciejewska-Karłowska, Agnieszka; Zarębska, Aleksandra; Leońska-Duniec, Agata; Jastrzębski, Zbigniew; Bishop, David J; Eynon, Nir

2015-01-01

The A1470T polymorphism (rs1049434) in the monocarboxylate (lactate/pyruvate) transporter 1 gene (MCT1) has been suggested to influence athletic performance in the general population. We compared genotype distributions and allele frequencies of the MCT1 gene A1470T polymorphism between endurance athletes, sprint/power athletes and matched controls. We also examined the association between the MCT1 A1470T and the athletes' competition level ('elite' and 'national' level). The study involved endurance athletes (n=112), sprint/power athletes (n=100), and unrelated sedentary controls (n=621), all Caucasians. Genomic DNA was extracted from buccal epithelium using a standard protocol. We conducted Fisher's exact tests and multinomial logistic regression analyses to assess the association between MCT1 genotype and athletic status/competition level. Sprint/power athletes were more likely than controls to possess the minor T allele (TT genotype compared to the AA [p<0.001]; TT or AT compared to the AA [p=0.007]; TT compared to both AA and AT genotypes [p<0.001]). Likewise, sprint/power athletes were more likely than endurance athletes to have the TT genotype compared to the AA (p=0.029) and the TT compared to both AA and AT genotypes (p=0.027). Furthermore, elite sprint/power athletes were more likely than national-level athletes to have the TT genotype compared to the AA (p=0.044), and more likely to have the TT genotype compared to both AA and AT genotypes (recessive model) (p=0.045). The MCT1 TT genotype is associated with elite sprint/power athletic status. Future studies are encouraged to replicate these findings in other elite athlete cohorts. Copyright © 2013 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

An 8bp indel in exon 1 of Ghrelin gene associated with chicken growth.

PubMed

Fang, Meixia; Nie, Qinghua; Luo, Chenglong; Zhang, Dexiang; Zhang, Xiquan

2007-04-01

Ghrelin, acts as the endogenous ligand for growth hormone secretagogues receptor (GHS-R), is a novel growth hormone (GH) releasing peptide with reported effects on food intake in chickens. In this study, an 8 bp indel polymorphism in exon 1 of the chicken Ghrelin (cGHRL) gene was genotyped in a F(2) designed full-sib population to analyze its associations with chicken growth and carcass traits. Later, mRNA level in the proventriculus was determined by real-time PCR to reveal the expression feature of cGHRL gene. Result showed that this 8 bp indel was significantly associated with body weight at the age of 28 days (BW28) and 56 days (BW56), eviscerated weight (EW) and leg muscle weight (LMW) (P<0.05), highly significantly associated with hatch weight (HW), BW14, 21, 35, 42, 49, 90 and body length (BL), dressed weight (DW), eviscerated weight with giblet (EWG), wing weight (WW), breast muscle weight (BMW) and head and neck weight (HNW) (P<0.01). Meanwhile, A allele (with 'CTAACCTG') was positive for chicken growth as individuals with AA genotype had the highest value of all traits. Analysis on cGhrelin mRNA level revealed that it differed significantly among individuals with three genotypes (P<0.05). Individuals with AB genotype had the highest mRNA level, whereas that of AA had the lowest one. It was concluded that this 8 bp indel of cGHRL gene was significantly associated with most body weight and body composition traits, and negative effect of endogenous Ghrelin on chicken growth were indicated by this study.

Phenolic profiles and their contribution to the antioxidant activity of selected chickpea genotypes from Mexico and ICRISAT collections.

PubMed

Quintero-Soto, Maria F; Saracho-Peña, Ana G; Chavez-Ontiveros, Jeanett; Garzon-Tiznado, Jose A; Pineda-Hidalgo, Karen V; Delgado-Vargas, Francisco; Lopez-Valenzuela, Jose A

2018-06-01

Chickpea (Cicer arietinum L.) genotypes, nine kabuli from Mexico and 9 desi from other countries, were investigated for their phenolic profiles and antioxidant activity (AA). Phenolics in methanol extracts (ME) were analyzed by ultra-performance liquid chromatography coupled to diode array detection and mass spectrometry (UPLC-DAD-MS), whereas the AA was measured as Trolox equivalents (TE) by ABTS, DPPH and FRAP methods. Twenty phenolic compounds were identified in the ME and their levels showed a great variability among the chickpea genotypes. Phenolic acids and flavonoids were the most abundant compounds in kabuli and desi genotypes, respectively. The AA values (μmol TE/ 100 g dw) by ABTS (278-2417), DPPH (52-1650), and FRAP (41-1181) were mainly associated with the content of sinapic acid hexoside, gallic acid, myricetin, quercetin, catechin, and isorhamnetin, suggesting they are the main compounds responsible for the AA. The sum of the AA obtained for standards of these compounds evaluated at the concentration found in the extracts accounted for 34.3, 69.8, and 47.0% of the AA in the extract by ABTS, DPPH, and FRAP, respectively. In the AA by DPPH, most of the mixtures of these compounds resulted in synergistic interactions. Three desi genotypes with black seeds (ICC 4418, ICC 6306, and ICC 3761) showed the highest AA and flavonoids content, whereas the most promising kabuli genotypes were Surutato 77, Bco. Sin. 92, and Blanoro that showed the highest values of phenolic acids. These genotypes represent good sources of antioxidants for the improvement of nutraceutical properties in chickpea.

Genotyping of β-Lactoglobulin gene by PCR-RFLP in Sahiwal and Tharparkar cattle breeds

PubMed Central

Rachagani, Satyanarayana; Gupta, Ishwar Dayal; Gupta, Neelam; Gupta, SC

2006-01-01

Background Improvement of efficiency and economic returns is an important goal in dairy farming, as in any agricultural enterprise. The primary goal of dairy industry has been to identify an efficient and economical way of increasing milk production and its constituents without increasing the size of the dairy herd. Selection of animals with desirable genotypes and mating them to produce the next generation has been the basis of livestock improvement and this would continue to remain the same in the coming years. The use of polymorphic genes as detectable molecular markers is a promising alternative to the current methods of trait selection once these genes are proven to be associated with traits of interest in animals. The point mutations in exon IV of bovine β-Lactoglobulin gene determine two allelic variants A and B. These variants were distinguished by Polymerase Chain Reaction and Restriction Fragment Length Polymorphism (PCR-RFLP) analysis in two indigenous Bos indicus breeds viz. Sahiwal and Tharparkar cattle. DNA samples (228 in Sahiwal and 86 in Tharparkar) were analyzed for allelic variants of β-Lactoglobulin gene. Polymorphism was detected by digestion of PCR amplified products with Hae III enzyme, and separation on 12% non-denaturing gels and resolved by silver staining. Results The allele B of β-Lactoglobulin occurred at a higher frequency than the allele A in both Sahiwal and Tharparkar breeds. The genotypic frequencies of AA, AB, and BB in Sahiwal and Tharparkar breeds were 0.031, 0.276, 0.693 and 0.023, 0.733, 0.244 respectively. Frequencies of A and B alleles were 0.17 and 0.83, and 0.39 and 0.61 in Sahiwal and Tharparkar breeds respectively. The Chi-square test results (at one degree of freedom at one per cent level) revealed that the Tharparkar population was not in Hardy-Weinberg equilibrium as there was a continuous migration of animals in the herd studied, where as, the results are not significant for the Sahiwal population. Conclusion Genotype frequencies of AA were the lowest compared to that of BB genotype in Sahiwal cattle while AB genotypes were more frequent in Tharparkar cattle. The frequency of A allele was found to be lower than that of B allele in both the breeds studied. These results further confirm that Bos indicus cattle are predominantly of β-Lactoglobulin B type than Bos taurus breeds. PMID:16725039

American foulbrood of the honey bee: occurrence and distribution of different genotypes of Paenibacillus larvae in the administrative district of Arnsberg (North Rhine-Westphalia).

PubMed

Peters, M; Kilwinski, J; Beringhoff, A; Reckling, D; Genersch, E

2006-03-01

Between March 2003 and October 2004, Paenibacillus larvae, the aetiological agent of American foulbrood disease of the honey bee, was isolated from broodcombs and honey samples of 54 apiaries in the administrative district of Arnsberg (North Rhine-Westphalia, Germany). Genotyping of 176 P. larvae isolates with repetitive element polymerase chain reaction fingerprinting (rep-PCR) using BOX A1R and MBO REP1 primers revealed five different genotypes (AB, Ab, ab, ass, Acapital BE, Cyrillic). In samples of three apiaries, more than one genotype was detected. A combination of two genotypes was isolated from honey samples of the same hive two times (ab/ass and Ab/ab). The five genotypes were not randomly distributed in the district, but revealed a certain geographical clustering. Possible factors with impact on the genotype diversity and the distribution pattern are discussed.

Cytogenetic evidence of mixed disomic and polysomic inheritance in an allotetraploid (AABB) Musa genotype

PubMed Central

Jeridi, Mouna; Perrier, Xavier; Rodier-Goud, Marguerite; Ferchichi, Ali; D'Hont, Angélique; Bakry, Frédéric

2012-01-01

Background and Aims Edible bananas originated mainly from two wild species, Musa acuminata Colla (AA) and Musa balbisiana Colla (BB), and triploid cultivars with an AAA, AAB or ABB genome are the most widely used. In the present study, chromosome pairing affinities are investigated in a sterile AB Indian variety and in its fertile colchicine-induced allotetraploid (AABB) derivative to determine the inheritance pattern of the tetraploid genotype. The potential implications of interspecific recombination and chromosomal composition of diploid gametes for Musa improvement are presented. Methods The pairing of different chromosome sets at diploid and tetraploid levels was investigated through a combination of conventional cytogenetic and genomic in-situ hybridization (GISH) analyses of meiotic chromosomes, leading to a likelihood model of the pairing behaviour. GISH analysis of mitotic chromosomes was also conducted to reveal the chromosome constitution of hybrids derived from crosses involving the allotetraploid genotype. Key Results Analysis of chromosome associations at both ploidy levels suggested that the newly formed allotetraploid behaves as a ‘segmental allotetraploid’ with three chromosome sets in a tetrasomic pattern, three sets in a likely disomic pattern and the five remaining sets in an intermediate pattern. Balanced and unbalanced diploid gametes were detected in progenies, with the chromosome constitution appearing to be more homogenous in pollen than in ovules. Conclusions Colchicine-induced allotetraploids in Musa provide access to the genetic background of natural AB varieties. The segmental inheritance pattern exhibited by the AABB allotetraploid genotype implies chromosome exchanges between M. acuminata and M. balbisiana species and opens new horizons for reciprocal transfer of valuable alleles. PMID:23087127

Cytogenetic evidence of mixed disomic and polysomic inheritance in an allotetraploid (AABB) Musa genotype.

PubMed

Jeridi, Mouna; Perrier, Xavier; Rodier-Goud, Marguerite; Ferchichi, Ali; D'Hont, Angélique; Bakry, Frédéric

2012-12-01

Edible bananas originated mainly from two wild species, Musa acuminata Colla (AA) and Musa balbisiana Colla (BB), and triploid cultivars with an AAA, AAB or ABB genome are the most widely used. In the present study, chromosome pairing affinities are investigated in a sterile AB Indian variety and in its fertile colchicine-induced allotetraploid (AABB) derivative to determine the inheritance pattern of the tetraploid genotype. The potential implications of interspecific recombination and chromosomal composition of diploid gametes for Musa improvement are presented. The pairing of different chromosome sets at diploid and tetraploid levels was investigated through a combination of conventional cytogenetic and genomic in-situ hybridization (GISH) analyses of meiotic chromosomes, leading to a likelihood model of the pairing behaviour. GISH analysis of mitotic chromosomes was also conducted to reveal the chromosome constitution of hybrids derived from crosses involving the allotetraploid genotype. Analysis of chromosome associations at both ploidy levels suggested that the newly formed allotetraploid behaves as a 'segmental allotetraploid' with three chromosome sets in a tetrasomic pattern, three sets in a likely disomic pattern and the five remaining sets in an intermediate pattern. Balanced and unbalanced diploid gametes were detected in progenies, with the chromosome constitution appearing to be more homogenous in pollen than in ovules. Colchicine-induced allotetraploids in Musa provide access to the genetic background of natural AB varieties. The segmental inheritance pattern exhibited by the AABB allotetraploid genotype implies chromosome exchanges between M. acuminata and M. balbisiana species and opens new horizons for reciprocal transfer of valuable alleles.

Genetic analysis of interleukin 18 gene polymorphisms in alopecia areata.

PubMed

Celik, Sumeyya Deniz; Ates, Omer

2018-06-01

Alopecia areata (AA), which appears as nonscarring hair shedding on any hair-bearing area, is a common organ-specific autoimmune condition. Cytokines have important roles in the development of AA. Interleukin (IL) 18 is a significant proinflammatory cytokine that was found higher in the patients with AA. We aimed to investigate whether the IL-18 (rs187238 and rs1946518) single nucleotide polymorphisms (SNPs) may be associated with AA and/or clinical outcome of patients with AA in Turkish population. Genotyping of rs187238 and rs1946518 SNPs were detected using sequence-specific primer-polymerase chain reaction (SSP-PCR) method in 200 patients with AA and 200 control subjects. The genotype distribution of rs1946518 (-607C>A) SNP was found to be statistically significantly different among patients with AA and controls (P = .0008). Distribution of CC+CA genotypes and frequency of -607/allele C of rs1946518 SNP were higher in patients with AA (P = .001, P = .001, respectively). The genotype distribution of rs187238 (-137G>C) SNP was found to be statistically significantly different among patients with AA and control subjects (P = .0014). Distribution of GG genotype and frequency of -137/allele G of rs187238 SNP were higher in patients with AA (P = .0003, P = .001, respectively). The rs1946518 (-607C>A) and rs187238 (-137G>C) polymorphisms were found associated with alopecia areata disease. The study suggests that IL-18 rs187238 and rs1946518 SNPs may be the cause of the AA susceptibility. © 2018 Wiley Periodicals, Inc.

Identification of polymorphism in exons 7 and 12 of lactoferrin gene and its association with incidence of clinical mastitis in Murrah buffalo.

PubMed

Dinesh, Krishanender; Verma, Archana; Das Gupta, Ishwar; Thakur, Yash Pal; Verma, Nishant; Arya, Ashwani

2015-04-01

Lactoferrin gene is one of the important candidate genes for mastitis resistance. The gene is located on chromosome BTA 22 and consists of 17 exons spanning over 34.5 kb of genomic DNA. The present study was undertaken with the objectives to identify allelic variants in exons 7 and 12 of lactoferrin gene and to analyze association between its genetic variants and incidence of clinical mastitis in Murrah buffalo. The amplification of exons 7 and 12 of lactoferrin gene yielded amplicons of 232- and 461-bp sizes. PCR-restriction fragment length polymorphism (RFLP) analysis of 232-bp amplicon using BccI restriction enzyme revealed three genotypes (AA, AB, and BB) with frequencies of 0.62, 0.22, and 0.16, respectively. The frequencies of two alleles, A and B, were estimated as 0.73 and 0.27. Hpy188I-RFLP for 461-bp amplicon revealed polymorphism with three genotypes, CC, CD, and DD, with respective frequencies of 0.06, 0.39, and 0.56, whereas frequencies for C and D alleles were 0.25 and 0.75. The chi-square (χ(2)) analysis revealed a significant association between incidence of clinical mastitis and genetic variants of exon 7, and animals of AA genotype of exon 7 were found to be least susceptible to mastitis. The findings indicate potential scope for incorporation of lactoferrin gene in selection and breeding of Murrah buffaloes for improved genetic resistance to mastitis.

Bt Proteins Have No Detrimental Effects on Larvae of the Green Lacewing, Chrysopa pallens (Rambur) (Neuroptera: Chrysopidae).

PubMed

Ali, I; Zhang, S; Muhammad, M S; Iqbal, M; Cui, J-J J-J

2018-06-01

Biosafety of a genetically modified crop is required to be assessed prior to its commercialization. For this, a suitable artificial diet was developed and used to establish a dietary exposure test for assessing the toxicity of midgut-active Bt insecticidal proteins on Chrysopa pallens (Rambur). Subsequently, this dietary exposure test was used to evaluate the toxicity of the proteins Cry1Ab, Cry1Ac, Cry1Ah, Cry1Ca, Cry1F, Cry2Aa, Cry2Ab, and Vip3Aa on C. pallens larvae. Temporal stability, bioactivity, and the intake of the insecticidal proteins were confirmed by enzyme-linked immunosorbent assay and a sensitive-insect bioassay. The life history characteristics, such as survival, pupation, adult emergence, 7-day larval weight, larval developmental time, and emerged male and female fresh weights remained unaffected, when C. pallens were fed the pure artificial diet (negative control) and the artificial diets containing 200 μg/g of each purified protein: Cry1Ab, Cry1Ac, Cry1Ah, Cry1Ca, Cry1F, Cry2Aa, Cry2Ab, or Vip3Aa. On the contrary, all of the life history characteristics of C. pallens larvae were adversely affected when fed artificial diet containing boric acid (positive control). The results demonstrate that diets containing the tested concentrations of Cry1Ab, Cry1Ac, Cry1Ah, Cry1Ca, Cry1F, Cry2Aa, Cry2Ab, and Vip3Aa have null effects on C. pallens larvae. The outcome indicates that genetically modified crops expressing the tested Bt proteins are safe for the lacewing, C. pallens.

Association of a novel regulatory polymorphism (-938C>A) in the BCL2 gene promoter with disease progression and survival in chronic lymphocytic leukemia.

PubMed

Nückel, Holger; Frey, Ulrich H; Bau, Maja; Sellmann, Ludger; Stanelle, Jens; Dürig, Jan; Jöckel, Karl-Heinz; Dührsen, Ulrich; Siffert, Winfried

2007-01-01

Bcl-2 plays a key role in the regulation of apoptosis. We investigated the role of a novel regulatory single-nucleotide polymorphism (-938C>A) in the inhibitory P2 BCL2 promoter in B-cell chronic lymphocytic leukemia (B-CLL). The -938C allele displayed significantly increased BCL2 promoter activity and binding of nuclear proteins compared with the A allele. Concomitantly, Bcl-2 protein expression in B cells from CLL patients carrying the -938 AA genotype was significantly increased compared with CC genotypes. Genotype distribution between 123 CLL patients (42 AA, 55 AC, 26 CC) and 120 genotyped healthy controls (36 AA, 63 AC, 21 CC) was not significantly different, suggesting that genotypes of this polymorphism do not increase the susceptibility for B-CLL. However, median time from first diagnosis to initiation of chemotherapy and median overall survival were significantly shorter in patients with -938AA genotype (38 and 199 months, respectively) compared with AC/CC genotypes (120 and 321 months, respectively; P = .008 and P = .003, respectively). Multivariable Cox regression identified the BCL2-938AA genotype as an independent prognostic factor for the time to first treatment (hazard ratio [HR] 1.9; P = .034) together with disease stage at diagnosis (HR 2.5; P = .004) and ZAP-70 status (HR 3.0; P = .001). The BCL2-938AA genotype is associated with increased Bcl-2 expression and a novel unfavorable genetic marker in patients with B-CLL.

Amino acid digestibility of different rye genotypes in caecectomised laying hens.

PubMed

Zuber, Tobias; Miedaner, Thomas; Rosenfelder, Pia; Rodehutscord, Markus

2016-12-01

This study investigated the variability of amino acid (AA) digestibility of rye grains in laying hens. Relationships between AA digestibility and physical properties (thousand seed weight, test weight, falling number, and extract viscoelasticity), chemical composition (proximate nutrients, non-starch polysaccharides, AA, minerals, and inositol phosphates), gross energy concentration, and in vitro solubility of nitrogen (N) of the grains were also examined. Twenty rye genotypes were grown under standardised agronomic and environmental conditions as part of a collaborative research project known as "GrainUp". Each genotype was added to a basal diet at 500 g/kg at the expense of maize starch to produce 20 rye diets. The experimental design comprised four Latin Squares (6 × 6) distributed over two runs, resulting in 12 experimental periods. Caecectomised laying hens (LSL-Classic) were individually kept in metabolism cages. Excreta were collected quantitatively for 4 d, and AA digestibility of the rye genotypes was determined using a regression approach. The digestibility of AA was generally low but varied significantly among the 20 rye genotypes, especially for Lys (digestibility range 35-59%), Met (57-75%), Thr (34-54%), and Trp (36-71%). Nevertheless, physical and chemical characteristics as well as the in vitro solubility of N correlated in only a few cases with AA digestibility. Multiple linear regression was used to calculate equations to predict AA digestibility based on the analysed characteristics. However, their explanatory power, as judged by the adjusted R(2), was not sufficiently precise for practical application (below 0.6 for most AA). In conclusion, the AA digestibility of rye grain is generally low and varies significantly between crop genotypes. Equations based on its physical and chemical characteristics are not sufficiently precise to be useful for feed formulation.

The influence of casein haplotype on morphometric characteristics of fat globules and fatty acid composition of milk in Italian Holstein cows.

PubMed

Perna, Annamaria; Intaglietta, Immacolata; Simonetti, Amalia; Gambacorta, Emilio

2016-04-01

The aim of this work was to investigate the effect of casein haplotypes (αS1-, β-, and κ-caseins) on morphometric characteristics of fat globules and fatty acid composition of Italian Holstein milk. Casein haplotypes were determined by isoelectric focusing; milk fat globule size was measured by using a fluorescence microscope; and fatty acid profile was determined by gas chromatography. Casein haplotype significantly affected the fat globule size, the percentage incidence of each globule size class on total measured milk fat globules, and fatty acid composition. A higher incidence of smaller milk fat globules was associated with the BB-A(2)A(2)-BB genotype (αS1-, β-, and κ-casein haplotypes, respectively), whereas small globules were not detected in BB-A(2)A(1)-AA milk, but that milk had the highest percentage of large globules. A higher content of monounsaturated fatty acids was associated with the BB-A(2)A(2)-AB genotype, whereas higher contents of conjugated linoleic acid and docosahexaenoic acid were detected in BB-A(1)A(1)-AA milk. Our results indicate that casein haplotype could affect fat characteristics and, therefore, the nutritional and technological quality of milk. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Methylenetetrahydrofolate reductase gene, homocysteine and coronary artery disease: the A1298C polymorphism does matter. Inferences from a case study (Madeira, Portugal).

PubMed

Freitas, Ana I; Mendonça, Isabel; Guerra, Graça; Brión, Maria; Reis, Roberto P; Carracedo, Angel; Brehm, António

2008-01-01

Elevated levels of plasma homocysteine, an independent risk factor and a strong predictor of mortality in patients with coronary artery disease (CAD), can result from nutritional deficiencies or genetic errors, including methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms. The contribution of these polymorphisms in the development of CAD remains controversial. We analysed the impact of MTHFR C677T and A1298C on fasting homocysteine and CAD in 298 CAD patients proved by angiography and 510 control subjects from the Island of Madeira (Portugal). After adjustment for other risk factors, plasma homocysteine remained independently correlated with CAD. Serum homocysteine was significantly higher in individuals with 677TT and 1298AA genotypes. There was no difference in the distribution of MTHFR677 genotypes between cases and controls but a significant increase in 1298AA prevalence was found in CAD patients. In spite of the clear effect of C677T mutation on elevated homocysteine levels we only found an association between 1298AA genotype and CAD in this population. The simultaneous presence of 677CT and 1298AA genotypes provides a significant risk of developing the disease, while the 1298AC genotype, combined with 677CC, shows a significant trend towards a decrease in CAD occurrence. The data shows an independent association between elevated levels of homocysteine and CAD. Both MTHFR polymorphisms are associated with increased fasting homocysteine (677TT and 1298AA genotypes), but only the 1298AA variant shows an increased prevalence in CAD group. Odds ratio seem to indicate that individuals with the MTHFR 1298AA genotype and the 677CT/1298AA compound genotype had a 1.6-fold increased risk for developing CAD suggesting a possible association of MTHFR polymorphisms with the risk of CAD in Madeira population.

Spectroscopic signatures of AA' and AB stacking of chemical vapor deposited bilayer MoS 2

DOE PAGES

Xia, Ming; Li, Bo; Yin, Kuibo; ...

2015-11-04

We discuss prominent resonance Raman and photoluminescence spectroscopic differences between AA'and AB stacked bilayer molybdenum disulfide (MoS 2) grown by chemical vapor deposition are reported. Bilayer MoS 2 islands consisting of the two stacking orders were obtained under identical growth conditions. Also, resonance Raman and photoluminescence spectra of AA' and AB stacked bilayer MoS 2 were obtained on Au nanopyramid surfaces under strong plasmon resonance. Both resonance Raman and photoluminescence spectra show distinct features indicating clear differences in interlayer interaction between these two phases. The implication of these findings on device applications based on spin and valley degrees of freedom.

Role of 'B-b' knob-hole interactions in fibrin binding to adsorbed fibrinogen.

PubMed

Geer, C B; Tripathy, A; Schoenfisch, M H; Lord, S T; Gorkun, O V

2007-12-01

The formation of a fibrin clot is supported by multiple interactions, including those between polymerization knobs 'A' and 'B' exposed by thrombin cleavage and polymerization holes 'a' and 'b' present in fibrinogen and fibrin. Although structural studies have defined the 'A-a' and 'B-b' interactions in part, it has not been possible to measure the affinities of individual knob-hole interactions in the absence of the other interactions occurring in fibrin. We designed experiments to determine the affinities of knob-hole interactions, either 'A-a' alone or 'A-a' and 'B-b' together. We used surface plasmon resonance to measure binding between adsorbed fibrinogen and soluble fibrin fragments containing 'A' knobs, desA-NDSK, or both 'A' and 'B' knobs, desAB-NDSK. The desA- and desAB-NDSK fragments bound to fibrinogen with statistically similar K(d)'s of 5.8 +/- 1.1 microm and 3.7 +/- 0.7 microm (P = 0.14), respectively. This binding was specific, as we saw no significant binding of NDSK, which has no exposed knobs. Moreover, the synthetic 'A' knob peptide GPRP and synthetic 'B' knob peptides GHRP and AHRPY, inhibited the binding of desA- and/or desAB-NDSK. The peptide inhibition findings show both 'A-a' and 'B-b' interactions participate in desAB-NDSK binding to fibrinogen, indicating 'B-b' interactions can occur simultaneously with 'A-a'. Furthermore, 'A-a' interactions are much stronger than 'B-b' because the affinity of desA-NDSK was not markedly different from desAB-NDSK.

Influence of genetic polymorphisms of IL23R, STAT3, IL12B, and STAT4 on the risk of aplastic anemia and the effect of immunosuppressive therapy.

PubMed

Zhao, Li; Zhu, Huanling; Han, Bing; Wang, Lixin; Sun, Yuming; Lu, Xiaojun; Huang, Chunyan; Tan, Bin; Chen, Chunxia; Qin, Li

2018-04-01

Studies have suggested that IL-23/STAT3 and IL-12/STAT4 signaling pathways associate with aplastic anemia (AA) occurrence. Polymorphisms in pathway-related genes may contribute to AA risk. In the current study, we investigated the association between polymorphisms in genes of IL23R, STAT3, IL12B, and STAT4 and occurrence, severity, and immunosuppressive outcome of AA in the Han population in southwest China. In the current 164 AA cases and 211 controls study, we found T allele and TT genotype of rs7574865 were more frequent in the cases than that in the controls. In the additive model, individual carrying rs7574865 T allele demonstrated a 37% (OR (95% CI) = 1.37 (1.02-1.85), Pper = 0.036) increased AA risk. In the recessive model, carrier with rs7574865 TT genotype showed a 2.08-fold increased AA risk (OR (95% CI) = 2.08 (1.14-3.70), Pper = 0.017). Additionally, we showed that G allele and GG genotype of rs11209032 were more frequent in the 88 non-severe AA cases than that in the 76 severe AA ones. Our study also found G allele and GG genotype of rs11209032, and GG-genotype of rs744166 associated with the immunosuppressive therapy outcome in AA patients. Current study results support that functional STAT4 (rs7574865), IL23R (rs11209032), and STAT3 (rs744166) variants may associate with occurrence, severity, and immunosuppressive outcome of AA in the Han population in southwest China.

A Western Corn Rootworm Cadherin-like Protein is not Involved in the Binding and Toxicity of Cry34/35Ab1 and Cry3Aa Bacillus Thuringiensis Proteins

USDA-ARS?s Scientific Manuscript database

The western corn rootworm (WCR) Diabrotica virgifera virgifera LeConte is an important insect pest of corn. Bacillus thuringiensis (Bt) insecticidal proteins Cry3Aa (as mCry3A) and Cry34Ab1/Cry35Ab1 have been expressed in transgenic corn and are used to control the insect in the U.S. To date, there ...

Influence of the 48867A>C (Asp358Ala) IL6R polymorphism on response to a lifestyle modification intervention in individuals with metabolic syndrome.

PubMed

Vargas, V R A; Bonatto, S L; Macagnan, F E; Feoli, A M P; Alho, C S; Santos, N D V; Schmitt, V M

2013-02-28

We evaluated the response of individuals with metabolic syndrome to lifestyle modification intervention and examined the influence of the 48867A>C (Asp358Ala) IL6R (rs2228145) polymorphism on this response. Participants were randomly divided into two groups: NI, nutritional intervention; NIE, nutritional intervention and exercise practice. Intervention lasted three months and participants completed a comprehensive evaluation and had blood collected for biochemical measurements. Eighty-two sedentary individuals with at least three criteria for metabolic syndrome were included. Comparing metabolic syndrome parameters before and after intervention, a reduction of waist circumference was observed, although significant only for AA and AC genotypes. Also, a decrease in triglyceride levels was observed (significant for AA genotype individuals; for the AC genotype, only in the NIE group). Significant reduction of fasting glucose level was observed in all AA genotype individuals; for the AC genotype, only in the NI group. Systolic blood pressure showed significant reduction in AA and AC genotype individuals. After three months of lifestyle modification intervention, improvement in some of the metabolic syndrome parameters was observed, some associated with the IL6R genotype. At enrollment, participants with genotypes AA and AC showed more severe conditions regarding metabolic syndrome inclusion criteria, supporting previous reports that the A allele is a genetic risk factor. These individuals, however, had a better response to intervention compared to individuals with the CC genotype, suggesting that nutritional control and exercise practice could prevent risks associated with metabolic syndrome more efficiently in individuals bearing the A allele.

Development of a novel rapid immunochromatographic test specific for the H5 influenza virus.

PubMed

Miyagawa, Eiji; Kogaki, Hiroyuki; Uchida, Yoshiaki; Fujii, Nobuyuki; Shirakawa, Takashi; Sakoda, Yoshihrio; Kida, Hiroshi

2011-05-01

Three anti-H5 influenza virus monoclonal antibody (mAb) clones, IFH5-26, IFH5-115 and IFH5-136, were obtained by immunising a BALB/C mouse with inactivated A/duck/Hokkaido/Vac-1/04 (H5N1). These mAbs were found to recognise specifically the haemagglutinin (HA) epitope of the influenza H5 subtypes by western blotting with recombinant HAs; however, these mAbs have no neutralising activity for A/duck/Hokkaido/84/02 (H5N3) or A/Puerto Ric/8/34 (H1N1). Each epitope of these mAbs was a conformational epitope that was formed from the regions located between 46 to 60 amino acids (aa) and 312 to 322 aa for IFH5-115, from 101 to 113 aa and 268 to 273 aa for IFH5-136 and from 61 to 80 aa and 290 to 300 aa for IFH5-26. The epitopes were located in the loop regions between the receptor region and alpha-helix structure in haemagglutinin 1 (HA1). Influenza A virus H5-specific rapid immunochromatographic test kits were tested as solid phase antibody/alkaline phosphate-conjugated mAb in the following three combinations: IFH5-26/IFH5-115, IFH5-136/IFH5-26 and IFH5-136/IFH5-115. In every combination, only influenza A H5 subtypes were detected. For effective clinical application, rapid dual discrimination immunochromatographic test kits in combination with H5 HA-specific mAb, IFA5-26 and IFA5-115 and the influenza A NP NP-specific mAb, FVA2-11, were developed. The dual discrimination immunochromatographic tests kits detected influenza A virus H5 subtypes as H5 line-positive and all influenza A subtypes as A line-positive simultaneously. The dual discrimination immunochromatographic test kits may be useful for discriminating highly pathogenic avian influenza A H5N1 viruses from seasonal influenza A virus, as well as for confirming influenza infection status in human, avian and mammalian hosts. Copyright © 2011 Elsevier B.V. All rights reserved.

Differential clinical efficacy of anti-CD4 monoclonal antibodies in rat adjuvant arthritis is paralleled by differential influence on NF-κB binding activity and TNF-α secretion of T cells

PubMed Central

Pohlers, Dirk; Schmidt-Weber, Carsten B; Franch, Angels; Kuhlmann, Jürgen; Bräuer, Rolf; Emmrich, Frank; Kinne, Raimund W

2002-01-01

The aim of this study was to analyze the differential effects of three anti-CD4 monoclonal antibodies (mAbs) (with distinct epitope specifities) in the treatment of rat adjuvant arthritis (AA) and on T-cell function and signal transduction. Rat AA was preventively treated by intraperitoneal injection of the anti-CD4 mAbs W3/25, OX35, and RIB5/2 (on days -1, 0, 3, and 6, i.e. 1 day before AA induction, on the day of induction [day 0], and thereafter). The effects on T-cell reactivity in vivo (delayed-type hypersensitivity), ex vivo (ConA-induced proliferation), and in vitro (mixed lymphocyte culture) were assessed. The in vitro effects of anti-CD4 preincubation on T-cell receptor (TCR)/CD3-induced cytokine production and signal transduction were also analyzed. While preventive treatment with OX35 and W3/25 significantly ameliorated AA from the onset, treatment with RIB5/2 even accelerated the onset of AA by approximately 2 days (day 10), and ameliorated the arthritis only in the late phase (day 27). Differential clinical effects at the onset of AA were paralleled by a differential influence of the mAbs on T-cell functions, i.e. in comparison with OX35 and W3/25, the 'accelerating' mAb RIB5/2 failed to increase the delayed-type hypersentivity (DTH) to Mycobacterium tuberculosis, increased the in vitro tumor necrosis factor (TNF)-α secretion, and more strongly induced NF-κB binding activity after anti-CD4 preincubation and subsequent TCR/CD3-stimulation. Depending on their epitope specificity, different anti-CD4 mAbs differentially influence individual proinflammatory functions of T cells. This fine regulation may explain the differential efficacy in the treatment of AA and may contribute to the understanding of such treatments in other immunopathologies. PMID:12010568

Numerical study of A+A-->0 and A+B-->0 reactions with inertia.

PubMed

Romero, A H; Lacasta, A M; Sancho, J M; Lindenberg, Katja

2007-11-07

Using numerical methods the authors study the annihilation reactions A+A-->0 and A+B-->0 in one and two dimensions in the presence of inertial contributions to the motion of the particles. The particles move freely following Langevin dynamics at a fixed temperature. The authors focus on the role of friction.

[Analysis of POU1F1 gene polymorphisms in Qinchuan cattle and Chinese Holstein cattle].

PubMed

Yan, Lin-Jun; Liu, Bo; Fang, Xin-Tang; Chen, Hong; Zhang, Run-Feng; Bao, Bin; Zhang, Hai-Jun

2006-11-01

PCR-RFLP was applied to analyze the polymorphisms of POU1F1 gene in 218 Qinchuan cattle (QQ) and Chinese Holstein cattle (HC). Results demonstrated Hinf I polymorphisms in the 451 bp PCR product in the two populations. The frequencies of alleles A/B in QQ and HC populations were 0.232/0.768 and 0.132/0.868, respectively. The frequencies of three genotypes AA, AB and BB were 0.030/0.403/0.567 and 0.007/0.251/0.742, respectively. Qinchuan cattle population was at Hardy-Weinberg equilibrium at this locus, but Chinese Holstein cattle population was not. The gene heterozygosity/effective allele gene number/Shannon information entropy/polymorphism information content of Qinchuan cattle and Chinese Holstein cattle populations were listed for 0.356/1.553/0.541/0.292 and 0.229/1.297/0.390/0.203, respectively. All indices were higher in the Qinchuan cattle population.

The FOXO1 Gene-Obesity Interaction Increases the Risk of Type 2 Diabetes Mellitus in a Chinese Han Population.

PubMed

Gong, Lilin; Li, Rong; Ren, Wei; Wang, Zengchan; Wang, Zhihong; Yang, Maosheng; Zhang, Suhua

2017-02-01

Here, we aimed to study the effect of the forkhead box O1-insulin receptor substrate 2 (FOXO1-IRS2) gene interaction and the FOXO1 and IRS2 genes-environment interaction for the risk of type 2 diabetes mellitus (T2DM) in a Chinese Han population. We genotyped 7 polymorphism sites of FOXO1 gene and IRS2 gene in 780 unrelated Chinese Han people (474 cases of T2DM, 306 cases of healthy control). The risk of T2DM in individuals with AA genotype for rs7986407 and CC genotype for rs4581585 in FOXO1 gene was 2.092 and 2.57 times higher than that with GG genotype (odds ratio [OR] = 2.092; 95% confidence interval [CI] = 1.178-3.731; P = 0.011) and TT genotype (OR = 2.571; 95% CI = 1.404-4.695; P = 0.002), respectively. The risk of T2DM in individuals with GG genotype for Gly1057Asp in IRS2 gene was 1.42 times higher than that with AA genotype (OR = 1.422; 95% CI = 1.037-1.949; P = 0.029). The other 4 single nucleotide polymorphisms (SNPs) had no significant association with T2DM (P > 0.05). Multifactor dimensionality reduction (MDR) analysis showed that the interaction between SNPs rs7986407 and rs4325426 in FOXO1 gene and waist was the best model confirmed by interaction analysis, closely associating with T2DM. There was an increased risk for T2DM in the case of non-obesity with genotype combined AA/CC, AA/AC or AG/AA for rs7986407 and rs4325426, and obesity with genotype AA for rs7986407 or AA for rs4325426 (OR = 3.976; 95% CI = 1.156-13.675; P value from sign test [P(sign)] = 0.025; P value from permutation test [P(perm)] = 0.000-0.001). Together, this study indicates an association of FOXO1 and IRS2 gene polymorphisms with T2DM in Chinese Han population, supporting FOXO1-obesity interaction as a key factor for the risk of T2DM.

Association between Eight Functional Polymorphisms and Haplotypes in the Cholesterol Ester Transfer Protein (CETP) Gene and Dyslipidemia in National Minority Adults in the Far West Region of China.

PubMed

Guo, Shuxia; Hu, Yunhua; Ding, Yusong; Liu, Jiaming; Zhang, Mei; Ma, Rulin; Guo, Heng; Wang, Kui; He, Jia; Yan, Yizhong; Rui, Dongsheng; Sun, Feng; Mu, Lati; Niu, Qiang; Zhang, Jingyu; Li, Shugang

2015-12-16

We have investigated the relationship between the polymorphisms and haplotypes in the CETP gene, and dyslipidemia among the Xinjiang Kazak and Uyghur populations in China. A total of 712 patients with dyslipidemia and 764 control subjects of CETP gene polymorphism at rs12149545, rs3764261, rs1800775, rs711752, rs708272, rs289714, rs5882, and rs1801706 loci were studied by the Snapshot method, linkage disequilibrium analysis and haplotype construction. The results are as follows: (1) the minor allele of eight loci of frequencies in the two groups were different from other results of similar studies in other countries; (2) In the linear regression analysis, the HDL-C levels of rs708272 TT, rs1800775 AA, rs289714 CC and rs711752 AA genotypes were significantly higher than those of other genotypes, however, the rs3764261 GG and rs12149545 GG genotypes were significantly lower than those of other genotypes in the two ethnic groups. The HDL-C levels of the rs12149545 GG genotype were lower than those of other genotypes; (3) in the control group, the rs708272 CT genotype of TG levels were lower than in the CC genotype, the T genotype of LDL-C levels were lower than in the CC genotype, and the HDL-C levels were higher than in the CT genotype; the rs1800775 AC genotype of TG levels were higher than in the AA genotype, the rs711752 AG genotype of TG levels were lower than in the GG genotype, the AA genotype LDL-C levels were lower than in the GG genotype, and the HDL-C levels were higher than in the AG genotype; the rs1800775 AC genotype of TG levels were higher than in the AA genotype. In the dyslipidemia group, the rs708272 TT genotype of TC and LDL-C levels were higher than in the CT genotype and the rs3764261 TT genotype of TC levels were higher than in the GG genotype. The rs711752 AA genotype of TC and LDL-C levels were higher than in the AG genotype, and the rs12149545 AA genotype of TC and LDL-C levels were higher than in the GG genotype; (4) perfect Linkage Disequilibrium was observed for two sets of two SNPs: rs3764261 and rs12149545; rs711752 and rs708272. (5) Using SHEsis software analysis, the five A/T/A/A/T/C/A/G, A/T/A/A/T/T/G/A, G/G/A/G/C/C/G/G, G/G/C/G/C/C/A/G and G/G/C/G/C/T/G/G haplotypes were between dyslipidemia group and control group statistically significantly different (p < 0.05 in each case). The polymorphism of CETP genes rs708272, rs3764261, rs1800775, rs711752, rs12149545 was closely related to the dyslipidemia in the Xinjiang Uyghur and Kazakh ethnic groups; and the rs708272 T, rs3764261 T, rs711752 A, and rs12149545 A alleles could reduce risk of dyslipidemia in the Uyghur and Kazakh populations, however, the rs1800775 C allele showed risk factors.

Association between Eight Functional Polymorphisms and Haplotypes in the Cholesterol Ester Transfer Protein (CETP) Gene and Dyslipidemia in National Minority Adults in the Far West Region of China

PubMed Central

Guo, Shuxia; Hu, Yunhua; Ding, Yusong; Liu, Jiaming; Zhang, Mei; Ma, Rulin; Guo, Heng; Wang, Kui; He, Jia; Yan, Yizhong; Rui, Dongsheng; Sun, Feng; Mu, Lati; Niu, Qiang; Zhang, Jingyu; Li, Shugang

2015-01-01

We have investigated the relationship between the polymorphisms and haplotypes in the CETP gene, and dyslipidemia among the Xinjiang Kazak and Uyghur populations in China. A total of 712 patients with dyslipidemia and 764 control subjects of CETP gene polymorphism at rs12149545, rs3764261, rs1800775, rs711752, rs708272, rs289714, rs5882, and rs1801706 loci were studied by the Snapshot method, linkage disequilibrium analysis and haplotype construction. The results are as follows: (1) the minor allele of eight loci of frequencies in the two groups were different from other results of similar studies in other countries; (2) In the linear regression analysis, the HDL-C levels of rs708272 TT, rs1800775 AA, rs289714 CC and rs711752 AA genotypes were significantly higher than those of other genotypes, however, the rs3764261 GG and rs12149545 GG genotypes were significantly lower than those of other genotypes in the two ethnic groups. The HDL-C levels of the rs12149545 GG genotype were lower than those of other genotypes; (3) in the control group, the rs708272 CT genotype of TG levels were lower than in the CC genotype, the T genotype of LDL-C levels were lower than in the CC genotype, and the HDL-C levels were higher than in the CT genotype; the rs1800775 AC genotype of TG levels were higher than in the AA genotype, the rs711752 AG genotype of TG levels were lower than in the GG genotype, the AA genotype LDL-C levels were lower than in the GG genotype, and the HDL-C levels were higher than in the AG genotype; the rs1800775 AC genotype of TG levels were higher than in the AA genotype. In the dyslipidemia group, the rs708272 TT genotype of TC and LDL-C levels were higher than in the CT genotype and the rs3764261 TT genotype of TC levels were higher than in the GG genotype. The rs711752 AA genotype of TC and LDL-C levels were higher than in the AG genotype, and the rs12149545 AA genotype of TC and LDL-C levels were higher than in the GG genotype; (4) perfect Linkage Disequilibrium was observed for two sets of two SNPs: rs3764261 and rs12149545; rs711752 and rs708272. (5) Using SHEsis software analysis, the five A/T/A/A/T/C/A/G, A/T/A/A/T/T/G/A, G/G/A/G/C/C/G/G, G/G/C/G/C/C/A/G and G/G/C/G/C/T/G/G haplotypes were between dyslipidemia group and control group statistically significantly different (p < 0.05 in each case). The polymorphism of CETP genes rs708272, rs3764261, rs1800775, rs711752, rs12149545 was closely related to the dyslipidemia in the Xinjiang Uyghur and Kazakh ethnic groups; and the rs708272 T, rs3764261 T, rs711752 A, and rs12149545 A alleles could reduce risk of dyslipidemia in the Uyghur and Kazakh populations, however, the rs1800775 C allele showed risk factors. PMID:26694435

Association between overweight and obesity in schoolchildren with rs9939609 polymorphism (FTO) and family history for obesity.

PubMed

Reuter, Cézane Priscila; Burgos, Miria Suzana; Bernhard, Joana Carolina; Tornquist, Debora; Klinger, Elisa Inês; Borges, Tássia Silvana; Renner, Jane Dagmar Pollo; de Moura Valim, Andréia Rosane; de Mello, Elza Daniel

2016-01-01

To determine the association between overweight/obesity in schoolchildren with FTO rs9939609 polymorphism (fatmass and obesity associated) and family history of obesity. Cross-sectional study comprising a sample of 406 children aged 7-17 years in a city in southern Brazil. Overweight/obesity in schoolchildren was assessed by body mass index (BMI), and family history of obesity was self-reported by parents. Polymorphism genotyping was performed by real time PCR (polymerase chain reaction). The association between the nutritional status of schoolchildren with the presence of family obesity, stratified by polymorphism genotypes (AA [at-risk for obesity], AT, and TT), was assessed by prevalence ratio values (PR) through Poisson regression. Among schoolchildren with the AA genotype, 57.4% had overweight/obesity; the percentage was lower for the AT and TT genotypes (33.1% and 28.9%, respectively). Overweight/obesity in schoolchildren was associated with a family history of obesity, especially among children with the AA genotype. The prevalence was higher among those with an obese mother (PR: 1.28; p<0.001), obese maternal or paternal grandmother (PR: 1.22; p=0.047), and obese paternal grandfather (PR: 1.32; p<0.001). There is an association between the AA genotype of rs9939609 polymorphism and BMI among schoolchildren. The association between overweight/obesity in schoolchildren with a family history of obesity was found mainly among students with the AA genotype. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Associations of Leptin and Pituitary-Specific Transcription Factor Genes' Polymorphisms with Reproduction and Production Traits in Dairy Buffalo.

PubMed

Nasr, Maf; Awad, A; El Araby, I E

2016-08-01

This study aimed to detect the genetic variability in Leptin and Pit-1 genes using polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing also to explore their possible associations with reproductive and productive traits of Egyptian buffaloes. Regarding Leptin gene, three genotypes (AA, AG and GG) were identified with frequency of 0.54, 0.40 and 0.06, respectively, and the genotypes were distributed according to the Hardy-Weinberg equilibrium. Allele A was comparatively higher than G with frequency of 0.74 and 0.26, respectively. For Pit-1 gene, the association could not be performed due to the monomorphism (BB). The results showed that AA genotypes were found to be superior in most of production and reproduction traits. AA genotypes yielded more milk (2332.34 kg, p = 0.04) with higher fat% (6.10, p = 0.004) and fat yield (155.75 kg, p = 0.06), reach peak milk production at 42.19 days and required 2.19 services for conception in comparison with GG genotypes. Birthweight of animals with AA genotype was lesser than with GG genotype (39.35 and 43.67 kg, p = 0.02, respectively). The days open is numerically better in AA genotype animals (99.35 days), but the difference between the three genotypes was non-significant. The distinct significant associations reported in this study suggested that Leptin is reputable candidate genetic marker, which might be used to enhance animals' genetic potential for milk production in conjunction with reproduction. © 2016 Blackwell Verlag GmbH.

TNF-308 G/A polymorphism and risk of systemic lupus erythematosus in the Polish population.

PubMed

Piotrowski, Piotr; Wudarski, Mariusz; Sowińska, Anna; Olesińska, Marzena; Jagodziński, Paweł P

2015-09-01

Numerous studies have been performed with TNF-α-308 G/A (rs1800629) single nuclear polymorphism (SNP) to evaluate the risk of SLE in various ethnicities. However, the significance of TNF-α-308 G/A in both clinical and laboratory studies of the disease remains unclear. Using a high-resolution melting curve analysis, we assessed the prevalence of TNF-α-308 G/A SNP in SLE patients (n = 262) and controls (n = 528) in a Polish population. We also assessed the contribution of this SNP to various clinical symptoms and the presence of autoantibodies in SLE patients. The p-value obtained using a χ(2) test for the trend of TNF-α-308 G/A was statistically significant (ptrend = 0.0297). However, using logistic regression analysis for the presence of the HLA-DRB1*03:01 haplotype, we observed that the TNF-α-308 G/A SNP may be the DRB1*03:01-dependent risk factor of SLE in the Polish population. There was a significant contribution of TNF-α-308 A/A and A/G genotypes to arthritis OR = [2.692 (1.503-4.822, p = 0.0007, pcorr = 0.0119)] as well as renal SLE manifestation OR = [2.632 (1.575-4.397, p = 0.0002, pcorr = 0.0034)]. There was a significant association between TNF-α-308 A/A and A/G genotypes and the presence of anti-Ro antibodies (Ab) OR = 3.375(1.711-6.658, p = 0.0003, pcorr = 0.0051). However, the logistic regression analysis revealed that only renal manifestations and the presence of anti-anti-Ro antibodies remained significant after adjustment to the presence of the HLA-DRB1*03:01 haplotype. Our studies indicate that the TNF-α-308 G/A polymorphism may be a DRB1*03:01 haplotype-dependent genetic risk factor for SLE. However, this SNP was independently associated with renal manifestations and production of anti-Ro Ab.

Interleukin-1 Receptor Antagonist Polymorphism and Birth Timing: Pathway Analysis Among African American Women

PubMed Central

Gillespie, Shannon L.; Neal, Jeremy L.; Christian, Lisa M.; Szalacha, Laura A.; McCarthy, Donna O.; Salsberry, Pamela J.

2016-01-01

Background Timing of birth is a major determinant of newborn health. African American women are at increased risk for early birth, particularly via the inflammatory pathway. Variants of the IL1RN) gene, which encode the interleukin-1 receptor antagonist (IL-1Ra) protein, are implicated in early birth. The biological pathways linking these variables remain unclear. Evidence also suggests inflammatory pathways differ by race; however, studies among African American women are lacking. Objectives We assessed whether an IL1RN variant was associated with timing of birth among African American women and whether this relationship was mediated by lower anti-inflammatory IL-1Ra production or related to a decrease in inhibition of proinflammatory IL-1β production. Methods A candidate gene study using a prospective cohort design was used. We collected blood samples at 28–32 weeks gestation among African American women experiencing an uncomplicated pregnancy (N = 89). IL1RN SNP rs2637988 was genotyped and lipopolysaccharide-stimulated IL-1Ra and IL-1β production quantified. Medical record review determined timing of birth. Results Women with GG genotype gave birth earlier than women with AA/AG genotypes (b* = 0.21, p = .04). There was no indirect effect of IL1RN SNP rs2637988 allele status on timing of birth through IL-1Ra production, as evidenced by a nonsignificant product of coefficients in mediational analyses (ab = .006, 95% CI [-0.05, 0.13]. Women with GG genotype demonstrated less inhibition of IL-1β production for a unit positive difference in IL-1Ra production than women with AA/AG genotypes (b* = 0.93, p = .03). Greater IL-1β production at 28–32 weeks of pregnancy was marginally associated with earlier birth (b* = 0.21, p = .05). Discussion Women with GG genotype may be at risk for earlier birth due to diminished IL-1β inhibition, allowing for initiation of a robust inflammatory response upon even mild immune challenge. Study of inflammatory contributions to early birth among African American women may be key to identifying potential prognostic markers of risk and targeted preventive interventions. PMID:28252571

Development of a species-diagnostic marker and its application for population genetics studies of the stingless bee Trigona collina in Thailand.

PubMed

Theeraapisakkun, M; Klinbunga, S; Sittipraneed, S

2010-05-18

A molecular maker for authenticating species origin of the stingless bee (Trigona collina) was developed. Initially, amplified fragment length polymorphism analysis was made of 11 stingless bee species using 64 primer combinations. A 316-bp band found only in T. collina was cloned and sequenced. A primer pair (CUTc1-F/R) was designed and tested for species-specificity in 15 stingless bee species (239 nests). The expected 259-bp fragment was consistently amplified in all T. collina individuals (134/134 nests, 100%). Cross-species amplification was observed in T. pagdeni (43/51 nests; 84.3%), but not in other species. SSCP analysis of CUTc1 unambiguously differentiated T. collina from T. pagdeni. CUTc1 generated three genotypes in Thai T. collina (134 nests). An AA (259/259 bp) genotype was found in all stingless bees from the north (21 nests) and northeast (32 nests), and 23/28 nests from the Central region, whereas a BB (253/253 bp) genotype was observed in most samples from peninsular Thailand (42/53 nests). Heterozygotes exhibiting the AB (253/259 bp) genotype were observed in 5 of 28 nests from Prachuap Khiri Khan located slightly above the Kra ecotone and 11 of 53 nests originated further south of the Kra ecotone. Genotype distribution patterns of CUTc1 clearly indicated intraspecific population differentiation of Thai T. collina.

A screening of five Bacillus thuringiensis Vip3A proteins for their activity against lepidopteran pests.

PubMed

Ruiz de Escudero, Iñigo; Banyuls, Núria; Bel, Yolanda; Maeztu, Mireya; Escriche, Baltasar; Muñoz, Delia; Caballero, Primitivo; Ferré, Juan

2014-03-01

Five Bacillus thuringiensis Vip3A proteins (Vip3Aa, Vip3Ab, Vip3Ad, Vip3Ae and Vip3Af) and their corresponding trypsin-activated toxins were tested for their toxicity against eight lepidopteran pests: Agrotis ipsilon, Helicoverpa armigera, Mamestra brassicae, Spodoptera exigua, Spodoptera frugiperda, Spodoptera littoralis, Ostrinia nubilalis and Lobesia botrana. Toxicity was first tested at a high dose at 7 and 10 days. No major differences were found when comparing protoxins vs. trypsin-activated toxins. The proteins that were active against most of the insect species were Vip3Aa, Vip3Ae and Vip3Af, followed by Vip3Ab. Vip3Ad was non-toxic to any of the species tested. Considering the results by insect species, A. ipsilon, S. frugiperda and S. littoralis were susceptible to Vip3Aa, Vip3Ab, Vip3Ae and Vip3Af; S. exigua was susceptible to Vip3Aa and Vip3Ae, and moderately susceptible to Vip3Ab; M. brassicae and L. botrana were susceptible to Vip3Aa, Vip3Ae and Vip3Af; H. armigera was moderately susceptible to Vip3Aa, Vip3Ae and Vip3Af, and O. nubilalis was tolerant to all Vip3 proteins tested, although it showed some susceptibility to Vip3Af. The results obtained will help to design new combinations of insecticidal protein genes in transgenic crops or in recombinant bacteria for the control of insect pests. Copyright © 2014 Elsevier Inc. All rights reserved.

Thyroid Disorders Associated with Alopecia Areata in Egyptian Patients

PubMed Central

Bakry, Ola A; Basha, Mohamed A; El Shafiee, Maather K; Shehata, Wafaa A

2014-01-01

Context: Alopecia areata (AA) is a common form of localized, non-scarring hair loss. The etiopathogenesis of the disease is still unclear, but the role of autoimmunity is strongly suggested. AA is commonly associated with various autoimmune disorders; the most frequent among them is autoimmune thyroid disorders. Aim: To determine whether AA is associated with thyroid autoimmunity or thyroid function abnormalities in Egyptian patients. Materials and Methods: Fifty subjects with AA (37 males and 13 females) without clinical evidence of thyroid disorders were selected from Dermatology Outpatient Clinic, Menoufiya University Hospital, Menoufiya Governorate, Egypt, during the period from June 2009 to February 2010. They were divided into 3 groups according to severity of AA. Fifty age and sex-matched healthy volunteers (35 males and 15 females) were selected as a control group. Every case and control were subjected to history taking, complete general and dermatological examination. Venous blood samples were taken from cases and controls after taking their consents for measurement of thyroid stimulating hormone (TSH), free T3, freeT4 and detection of Anti-thyroglobulin Antibody (Tg-Ab) and Anti-thyroid Peroxidase Antibody (TPO-Ab). Results: Subclinical hypothyroidism was detected in 16% of cases. There were statistically significant differences between cases and controls regarding levels of TSH, free T3 and free T4. There were significant differences between cases and controls regarding the presence of Tg-Ab and TPO-Ab. Conclusions: Every patient with AA should be screened for thyroid functions and presence of thyroid autoantibodies even in absence of clinical manifestations suggestive of thyroid affection. PMID:24470660

Variability in amino acid digestibility of triticale grain from diverse genotypes as studied in cecectomized laying hens.

PubMed

Zuber, T; Maurer, H P; Möhring, J; Nautscher, N; Siegert, W; Rosenfelder, P; Rodehutscord, M

2016-12-01

Triticale, an anthropogenic hybrid grain, is increasing in importance as a feed grain for laying hens. However, our limited knowledge of its nutritional qualities and their impact on hen performance prevents optimization of its use. The present study investigated the digestibility of amino acids ( AA: ) in triticale grain in laying hens, and additionally examined relationships between AA digestibility and chemical and physical characteristics of the grain. Twenty genotypes of triticale were grown under standardized agronomic and environmental conditions and were characterized according to their physical properties (thousand-seed weight, test weight, falling number, extract viscoelasticity), chemical composition (proximate nutrients, non-starch polysaccharides, AA, minerals, inositol phosphates) and gross energy concentration. Additionally, the in vitro solubility of nitrogen was determined. The animal trial comprised 4 Latin Squares (6 × 6) distributed among 2 subsequent runs. Twelve cecectomized LSL-Classic hens were individually housed in metabolism cages and either fed a basal diet containing 500 g/kg cornstarch or one of 20 triticale diets, each replacing the cornstarch with one triticale genotype, for 8 d. During the last 4 d, feed intake was recorded and excreta were collected quantitatively. Amino acid digestibility of the triticale genotypes was calculated by linear regression. The digestibility of all AA differed significantly between the 20 genotypes, including Lys (digestibility range 68 to 80%), Met (77 to 86%), Thr (68 to 78%) and Trp (74 to 83%). However, AA digestibility only correlated with characteristics of the grain in few cases, without a consistent pattern among AA. Equations to predict AA digestibility based on the grain's physical and chemical characteristics were calculated by multiple linear regression. The explanatory power (adjusted R 2 ;) of these prediction equations was below 0.7 for most AA and thus not sufficiently precise to be suitable for practical application. In conclusion, AA digestibility of triticale grain is high overall in laying hens but varies significantly between crop genotypes. This variation could not be well explained by physical and chemical characteristics of the grain. © 2016 Poultry Science Association Inc.

Activity and cellular localization of amylases of rabbit cecal bacteria.

PubMed

Sirotek, K; Marounek, M; Suchorská, O

2006-01-01

Five 11-week-old rabbits, fed a commercial granulated feed, were slaughtered and cecal starch-degrading bacteria enumerated; total concentration of cultivable bacteria utilizing starch averaged 5.5 x 10(10) CFU/g. The activity and cellular localization of amylases was determined in 9 bacteria identified as Actinomyces israeli (strains AA2 and AD4), Bacteroides spp. (strain AA3), Dichelobacter nodosus (strain AA4), Mitsuokella multiacidus (strain AA6), Eubacterium spp. (strains AA7 and AB2), Clostridium spp. (strains AD1 and AA5). Four strains (AA3, AA4, AA5, AD4) produced extracellular amylases with an activity of 26-35 micromol of reducing sugars per h per mg of protein; in five strains (AA2, AA6, AA7, AB2, AD1) amylases were membrane-bound with an activity of 14-18 micromol of reducing sugars per h per mg of protein. All strains exhibited a low intracellular amylolytic activity. The pH optimum of amylases was 6.8-7.0. In strains producing extracellular amylases a substantial loss of viscosity was observed during incubations of cultivation supernatant with starch, similar to viscosity reduction in starch solutions treated with alpha-amylase; this indicates an endo-type (random cleavage) of extracellular amylase reaction in the bacteria under study. No strain possessed glucoamylase activity.

In vitro neutralization of HCV by goat antibodies against peptides encompassing regions downstream of HVR-1 of E2 glycoprotein.

PubMed

Tabll, Ashraf A; Atef, Khaled; Bader El Din, Noha G; El Abd, Yasmine S; Salem, Ahmed; Sayed, Ahmed A; Dawood, Reham M; Omran, Moataza H; El-Awady, Mostafa K

2014-01-01

This article aims at testing several in vitro systems with various viral sources and cell lines for propagation of HCV to evaluate goat antibodies raised against three E2 epitopes in viral neutralization experiments. Four human cell lines (Huh-7, Huh-7.5, HepG2, and CaCo2) were tested using two different HCV viral sources; Genotype 4 infected sera and J6/JFH HCV cc particles. Neutralization capacity of goat Abs against conserved E2 epitopes; p412 (a.a 412-419), p517 (a.a 517-531), and p430 (a.a 430-447) were examined in the above mentioned in vitro systems. Although infection with patients' sera seems to mimic the in vitro situation, it has limited replication rates as compared with HCV cc particularly in Huh7.5 cells. Non-HCV adapted Huh-7 cells were also found susceptible for transfection with J6/JFH virus but at much slower kinetics. The results of the neutralization assay showed that anti p412 and anti p517 were highly neutralizing to HCVcc. Our data demonstrate that antibodies directed against the viral surface glycoprotein E2 reduced the infectivity of the J6/JFH virus and are promising agents for immunotherapy and HCV vaccine development.

HPV genotypes and cervical intraepithelial neoplasia in a multiethnic cohort in the southeastern USA.

PubMed

Vidal, Adriana C; Smith, Jennifer S; Valea, Fidel; Bentley, Rex; Gradison, Maggie; Yarnall, Kimberly S H; Ford, Anne; Overcash, Francine; Grant, Kathy; Murphy, Susan K; Hoyo, Cathrine

2014-08-01

For poorly understood reasons, invasive cervical cancer (ICC) incidence and mortality rates are higher in women of African descent. Oncogenic human papillomavirus (HPV) genotypes distribution may vary between European American (EA) and African-American (AA) women and may contribute to differences in ICC incidence. The current study aimed at disentangling differences in HPV distribution among AA and EA women. Five-hundred and seventy-two women were enrolled at the time of colposcopic evaluation following an abnormal liquid-based cytology screen. HPV infections were detected using HPV linear array, and chi-squared tests and linear regression models were used to compare HPV genotypes across racial/ethnic groups by CIN status. Of the 572 participants, 494 (86 %) had detectable HPV; 245 (43 %) had no CIN lesion, 239 (42 %) had CIN1, and 88 (15 %) had CIN2/3. Seventy-three percent of all women were infected with multiple HPV genotypes. After adjusting for race, age, parity, income, oral contraception use, and current smoking, AAs were two times less likely to harbor HPV 16/18 (OR 0.48, 95 % CI 0.21-0.94, p = 0.03) when all women were considered. This association remained unchanged when only women with CIN2/3 lesions were examined (OR 0.22, 95 % CI 0.05-0.95, p = 0.04). The most frequent high-risk HPV genotypes detected among EAs were 16, 18, 56, 39, and 66, while HPV genotypes 33, 35, 45, 58, and 68 were the most frequent ones detected in AAs. Our data suggest that while HPV 16/18 are the most common genotypes among EA women with CIN, AAs may harbor different genotypes.

Ab-initio calculation of electronic structure and optical properties of AB-stacked bilayer α-graphyne

NASA Astrophysics Data System (ADS)

Behzad, Somayeh

2016-09-01

Monolayer α-graphyne is a new two-dimensional carbon allotrope with many special features. In this work the electronic properties of AA- and AB-stacked bilayers of this material and then the optical properties are studied, using first principle plane wave method. The electronic spectrum has two Dirac cones for AA stacked bilayer α-graphyne. For AB-stacked bilayer, the interlayer interaction changes the linear bands into parabolic bands. The optical spectra of the most stable AB-stacked bilayer closely resemble to that of the monolayer, except for small shifts of peak positions and increasing of their intensity. For AB-stacked bilayer, a pronounced peak has been found at low energies under the perpendicular polarization. This peak can be clearly ascribed to the transitions at the Dirac point as a result of the small degeneracy lift in the band structure.

Preparation and Biological Activity of the Monoclonal Antibody against the Second Extracellular Loop of the Angiotensin II Type 1 Receptor

PubMed Central

Wei, Mingming; Zhao, Chengrui; Zhang, Suli; Wang, Li; Liu, Huirong; Ma, Xinliang

2016-01-01

The current study was to prepare a mouse-derived antibody against the angiotensin II type 1 receptor (AT1-mAb) based on monoclonal antibody technology, to provide a foundation for research on AT1-AA-positive diseases. Balb/C mice were actively immunized with the second extracellular loop of the angiotensin II type 1 receptor (AT1R-ECII). Then, mouse spleen lymphocytes were fused with myeloma cells and monoclonal hybridomas that secreted AT1-mAb were generated and cultured, after which those in logarithmic-phase were injected into the abdominal cavity of mice to retrieve the ascites. Highly purified AT1-mAb was isolated from mouse ascites after injection with 1 × 107 hybridomas. A greater amount of AT1-mAb was purified from mouse ascites compared to the cell supernatant of hybridomas. AT1-mAb purified from mouse ascites constricted the thoracic aorta of mice and increased the beat frequency of neonatal rat myocardial cells via the AT1R, identical to the effects of AT1-AA extracted from patients' sera. Murine blood pressure increased after intravenous injection of AT1-mAb via the tail vein. High purity and good biological activity of AT1-mAb can be obtained from mouse ascites after intraperitoneal injection of monoclonal hybridomas that secrete AT1-mAb. These data provide a simple tool for studying AT1-AA-positive diseases. PMID:27057554

[Association of leptin receptor gene polymorphrism with metabolic syndrome in older Han adults from major cities in China].

PubMed

Wu, Jinghuan; Zhuo, Qin; Chen, Xi; Tian, Yuan; Piao, Jianhua; Yang, Xiaoguang

2016-05-01

To investigate the relationship of leptin receptor gene rs1137100 and rs1137101 single nucleotide polymorphrism (SNP) with metabolic syndrome (MS) in older Han adults from major cities in China. A total of 2082 older Han adults were selected from 18 major cities including 15 provinces/municipalities of China National Nutrition and Health Survey in 2002. According to the MS definition proposed by Joint Interim Statement (JIS), the subjects were divided into MS and control groups. Plasma leptin and insulin levels were measured. The genotypes of rs1137100 and rs1137101 were detected by Taqman method. Association of genotypes of leptin receptor gene SNPs with MS was investigated. The MS group showed higher body mass index (BMI), waist circumference, fasting serum glucose, systolic blood pressure (SBP) and diastolic blood pressure (DBP), triglycerides (TG), serum total cholesterol (TC), insulin, homeostasis model of assessment for insulin resistence index (HOMA-IR) and leptin levels than those of control individuals, while the high density lipoprotein cholesterol (HDL-c) was significantly lower than the control group. The, GG, AA, GA genotypes distribution and the A allele frequency of rs1137100 and rs1137101 were similar between the two groups. The DBP and SBP level were obviously higher in AA genotype. The HDL-c concentration Was significantly lower in AA and GA + AA genotype. The AA and GA genotypes carriers in rs1137100 had similar risk for MS when comparing with the GG genotypes, and the OR values were 1.23 (95% CI 0.90-1.67) and 2.23 (95% CI 0.83-6.44), respectively. The AA and GA genotypes carriers in rs1137101 had similar risk for MS when comparing with the GG genotypes, and the OR values were 1.23 (95% CI 0.90-1.67) and 2.23 (95% CI 0.83-6.44), respectively. Leptin receptor genes rs1137100 and rs1137101 are not associated with pathogenesis of MS in older Han adults, but it may relate with hypertension or lipid abnormality.

CARD8 rs2043211 polymorphism is associated with gout in a Chinese male population.

PubMed

Chen, Ying; Ren, Xianfeng; Li, Changgui; Xing, Shichao; Fu, Zhengju; Yuan, Ying; Wang, Robin; Wang, Yangang; Lv, Wenshan

2015-01-01

BACKGROUND &AIM: Previous studies have suggested genetic factors are involved in the development of gout. We performed a case-control study to investigate the genetic association between CARD8 rs2043211 polymorphism and gout. A total of 396 male patients with gout and 403 age- and sex- matched healthy controls were included in this study. Genotyping was performed using TaqMan SNP Genotyping Assays. An association analysis was carried out using the χ² test. The genotype-phenotype analysis was also conducted. The genotype distribution of CARD8 rs2043211 polymorphism confirmed to HWE in the controls (P = 0.27). There was an obvious difference in the genotype distribution of CARD8 rs2043211 polymorphism between cases and controls (P = 0.017). In addition, there was an obvious association between CARD8 rs2043211 polymorphism and gout under the recessive comparison model (AA vs. OR = 0.65, 95%CI 0.47-0.88, P = 0.006). Patients carrying genotype TT of CARD8 rs2043211 polymorphism had higher triglycerides levels compared to those carrying the AA genotype (2.77±2.08 mmol/L vs. 2.07±1.15 mmol/L, P = 0.01). Patients with the TT genotype also had significantly higher systolic blood pressure compared with those with the AA genotype (142.11±21.10 mmHg vs. 135.38±14.66 mmHg, P = 0.03). Patients carrying TT genotype also had an increased risk of renal calculus compared with those carrying the AA genotype. CARD8 rs2043211 polymorphism is significantly associated with susceptibility to gout in Chinese Han males. © 2015 S. Karger AG, Basel.

Relative binding and biochemical effects of heterodimeric and homodimeric isoforms of platelet-derived growth factor in osteoblast-enriched cultures from fetal rat bone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Centrella, M.; McCarthy, T.L.; Kusmik, W.F.

1991-06-01

Platelet-derived growth factor (PDGF) exists as a homodimer or a heterodimer comprising either PDGF-A or PDGF-B subunits, and each isoform occurs in various tissues, including bone. Although the stimulatory effects of PDGF-BB have been studied in cultures of bone cells and intact bone fragments, the influence of other isoforms that may arise locally or systematically in vivo, has not been reported. Therefore recombinant human PDGF-BB, PDGF-AB, and PDGF-AA were evaluated in osteoblast-enriched cultures from fetal rat bone. Within 24 hours these factors produced a graded response in bone cell DNA and protein synthesis, with half-maximal effects at approximately 0.6, 2.1,more » and 4.8 nM PDGF-BB, PDGF-AB, and PDGF-AA, respectively. Increases in collagen and noncollagen protein synthesis were abrogated when DNA synthesis was blocked with hydroxyurea. Furthermore, each factor reduced alkaline phosphatase activity, PDGF-BB being the most inhibitory. Binding studies with 125I-PDGF-BB or 125I-PDGF-AA and each unlabeled PDGF isoform produced discrete ligand binding and displacement patterns: 125I-PDGF-BB binding was preferentially displaced by PDGF-BB (Ki approximately 0.7 nM), less by PDGF-AB (Ki approximately 2.3 nM) and poorly by PDGF-AA. In contrast, 125I-PDGF-AA binding was measurably reduced by PDGF-AA (Ki approximately 4.0 nM), but was more effectively displaced by PDGF-BB or PDGF-AB (each with Ki approximately 0.7 nM). These studies indicate that each PDGF isoform produces biochemical effects proportional to binding site occupancy and suggest that receptors that favor PDGF-B subunit binding preferentially mediate these results in osteoblast-enriched bone cell cultures.« less

The molecular relationship between antigenic domains and epitopes on hCG.

PubMed

Berger, Peter; Lapthorn, Adrian J

2016-08-01

Antigenic domains are defined to contain a limited number of neighboring epitopes recognized by antibodies (Abs) but their molecular relationship remains rather elusive. We thoroughly analyzed the antigenic surface of the important pregnancy and tumor marker human chorionic gonadotropin (hCG), a cystine knot (ck) growth factor, and set antigenic domains and epitopes in molecular relationships to each other. Antigenic domains on hCG, its free hCGα and hCGβ subunits are dependent on appropriate inherent molecular features such as molecular accessibility and protrusion indices that determine bulging structures accessible to Abs. The banana-shaped intact hCG comprises ∼7500Å(2) of antigenic surface with minimally five antigenic domains that encompass a continuum of overlapping non-linear composite epitopes, not taking into account the C-terminal peptide extension of hCGβ (hCGβCTP). Epitopes within an antigenic domain are defined by specific Abs, that bury nearly 1000Å(2) of surface accessible area on the antigen and recognize a few up to 15 amino acid (aa) residues, whereby between 2 and 5 of these provide the essential binding energy. Variability in Ab binding modes to the contact aa residues are responsible for the variation in affinity and intra- and inter-species specificity, e.g. cross-reactions with luteinizing hormone (LH). Each genetically distinct fragment antigen binding (Fab) defines its own epitope. Consequently, recognition of the same epitope by different Abs is only possible in cases of genetically identical sequences of its binding sites. Due to combinatorial V(D)J gene segment variability of heavy and light chains, Abs defining numerous epitopes within an antigenic domain can be generated by different individuals and species. Far more than hundred Abs against the immuno-dominant antigenic domains of either subunit at both ends of the hCG-molecule, the tips of peptide loops one and three (Ł1+3) protruding from the central ck, encompassing hCGβŁ1+3 (aa 20-25+64+68-81) and hCGαŁ1 (aa 13-22; Pro16, Phe17, Phe18) plus hCGαŁ3 (Met71, Phe74), respectively, have been identified in the two "ISOBM Tissue Differentiation-7 Workshops on hCG and Related Molecules" and in other studies. These Abs recognize distinct but overlapping epitopes with slightly different specificity profiles and affinities. Heterodimeric-specific epitopes involve neighboring αŁ1 plus βŁ2 (hCGβ44/45 and 47/48). Diagnostically important Abs recognize the middle of the molecule, the ck (aa Arg10, Arg60 and possibly Gln89) and the linear hCGβCTP "tail" (aa 135-145; Asp139, Pro144, Gln145), respectively. Identification of antigenic domains and of specific epitopes is essential for harmonization of Abs in methods that are used for reliable and robust hCG measurements for the management of pregnancy, pregnancy-related disease and tumors. Copyright © 2016. Published by Elsevier Ltd.

TNFalpha and IL-10 gene polymorphisms in inflammatory bowel disease. Association of -1082 AA low producer IL-10 genotype with steroid dependency.

PubMed

Castro-Santos, Patricia; Suarez, Ana; López-Rivas, Laureano; Mozo, Lourdes; Gutierrez, Carmen

2006-05-01

An altered production of cytokines underlies inflammatory bowel disease (IBD) susceptibility. Various polymorphisms at the IL-10 and TNFalpha gene promoters control cytokine production levels. The influence of these polymorphisms on susceptibility to ulcerative colitis (UC) and Crohn's disease (CD) and their association with clinical features were analyzed. Genetic polymorphisms of TNFalpha (-308 G/A) and IL-10 (-1082 G/A, -812 C/T, and -592 C/A) were determined using the LightCycler system with hybridization probes matched with one sequence variant. The study population included 99 UC patients, 146 CD patients, and 343 matched controls. We did not find association between TNFalpha or IL-10 gene polymorphisms and UC or CD susceptibility, though a slight influence of -1082*G allele in UC appearance was observed. In a stratified analysis, a highly significant association between the -1082 AA IL-10 genotype and the steroid dependency was observed in IBD (p < 0.0001), contributing both UC (p = 0.004) and CD (p = 0.003) to this association. In contrast, TNFalpha genotypes did not influence steroid dependency in IBD. Further, the contribution of cytokine genotypes and of clinical features to the appearance of steroid-dependent status (dependent variable) was studied by multivariate analysis. The steroid-dependent phenotype correlated in UC with extensive disease (p = 0.010) and with the low producer -1082 AA IL-10 genotype (p = 0.002) and in CD with penetrating disease (p = 0.010), arthritis (p = 0.011), and the -1082 AA IL-10 genotype (p = 0.006). The main conclusion is that carriage of the -1082 AA IL-10 genotype (low producer) is a relevant risk factor for developing steroid-dependent IBD.

Cyclooxygenase-2 polymorphisms and the risk of gastric cancer in various degrees of relationship in the Chinese Han population

PubMed Central

LI, YUCHUN; DAI, LIPING; ZHANG, JIANZHONG; WANG, PENG; CHAI, YURONG; YE, HUA; ZHANG, JIANYING; WANG, KAIJUAN

2012-01-01

A number of studies have shown that cyclooxygenase-2 (COX-2) gene polymorphisms were associated with gastric cancer. However, the results from different research groups have not been consistent. The present study aimed to investigate the association between polymorphisms of the cyclooxygenase-2 promoter region (-1195G>A, -765G>C) and gastric cancer patients with various degrees of relationship in the Chinese Han population. COX-2-1195G>A and COX-2-765G>C polymorphisms in 296 gastric cancer patients and 319 control family members were genotyped using polymerase chain reaction-restriction fragment length polymorphism. An increased risk of gastric cancer was observed in subjects with the COX-2-1195AA genotype (OR=2.03; 95% CI, 1.27–3.22), and the association strength decreased as the degree of relationship decreased. Stratification analysis revealed that the OR value of COX-2-1195AA genotype and A carriers exhibited synergy with Helicobacter pylori (H. pylori) infection (AA genotype: OR=2.96; 95% CI, 1.57–5.58; A carriers: OR=2.04; 95% CI, 1.18–3.52). No significant difference was found in each genotype of COX-2-765G>C between gastric cancer patients and control family members, as well as gastric cancer patients with various degrees of relationship. Our study demonstrated that the polymorphism of COX-2-1195AA genotype may be a risk factor for gastric cancer patients with various degrees of relationship among the Chinese Han population. H. pylori infection therefore may enhance the risk of gastric cancer in individuals with the COX-2-1195 AA genotype. PMID:22740864

Genetic Variations of COL4A1 Gene and Intracerebral Hemorrhage Outcome: A Cohort Study in a Chinese Han Population.

PubMed

Xia, Chao; Lin, Sen; Yang, Jie; He, Sha; Li, Hao; Liu, Ming; You, Chao

2018-05-01

To investigate the relationship between single nucleotide polymorphisms or haplotypes of COL4A1 gene and the outcome of intracerebral hemorrhage (ICH). In our study, 181 patients with hypertensive ICH were enrolled and followed up at 3 and 6 months. Outcome data included any cause of death and disability. Genomic DNA was extracted by DNA extraction kit, and the 6 single nucleotide polymorphism genotyping of the COL4A1 gene was detected through MassARRAY Analyzer. Unphased 3.1.4 and SPSS 19.0 were used to analyze the association between alleles, genotypes, and haplotypes of the COL4A1 gene and the outcomes of ICH. Of the 181 patients with hypertensive ICH, 12 were lost in follow-up, which accounted for 6.6%. Our association analysis showed that the rs532625 AA genotype of the COL4A1 gene may increase risk of disability at 3 months; the rs532625 A allele and AA genotype were association factors of the risk of disability at 6 months; the rs532625 AA genotype was an association factor of the risk of death/disability at 6 months. After adjusting for gender, age, coma, and severe neurologic deficits, only the rs532625 AA genotype was independently associated with the risk of disability at 3 and 6 months and the risk of death/disability at 6 months. Our study found that the rs532625 AA genotype in the COL4A1 gene was independently associated with the risk of disability at 3 and 6 months and death/disability at 6 months in a Chinese Han population. These conclusions need to be verified in future studies with larger samples. Copyright © 2018 Elsevier Inc. All rights reserved.

Effects of breed and casein genetic variants on protein profile in milk from Swedish Red, Danish Holstein, and Danish Jersey cows.

PubMed

Gustavsson, F; Buitenhuis, A J; Johansson, M; Bertelsen, H P; Glantz, M; Poulsen, N A; Lindmark Månsson, H; Stålhammar, H; Larsen, L B; Bendixen, C; Paulsson, M; Andrén, A

2014-01-01

In selecting cows for higher milk yields and milk quality, it is important to understand how these traits are affected by the bovine genome. The major milk proteins exhibit genetic polymorphism and these genetic variants can serve as markers for milk composition, milk production traits, and technological properties of milk. The aim of this study was to investigate the relationships between casein (CN) genetic variants and detailed protein composition in Swedish and Danish dairy milk. Milk and DNA samples were collected from approximately 400 individual cows each of 3 Scandinavian dairy breeds: Swedish Red (SR), Danish Holstein (DH), and Danish Jersey (DJ). The protein profile with relative concentrations of α-lactalbumin, β-lactoglobulin, and α(S1)-, α(S2)-, κ-, and β-CN was determined for each milk sample using capillary zone electrophoresis. The genetic variants of the α(S1)- (CSN1S1), β- (CSN2), and κ-CN (CSN3) genes for each cow were determined using TaqMan SNP genotyping assays (Applied Biosystems, Foster City, CA). Univariate statistical models were used to evaluate the effects of composite genetic variants, α(S1)-β-κ-CN, on the protein profile. The 3 studied Scandinavian breeds differed from each other regarding CN genotypes, with DH and SR having similar genotype frequencies, whereas the genotype frequencies in DJ differed from the other 2 breeds. The similarities in genotype frequencies of SR and DH and differences compared with DJ were also seen in milk production traits, gross milk composition, and protein profile. Frequencies of the most common composite α(S1)-β-κ-CN genotype BB/A(2)A(2)/AA were 30% in DH and 15% in SR, and cows that had this genotype gave milk with lower relative concentrations of κ- and β-CN and higher relative concentrations of αS-CN, than the majority of the other composite genotypes in SR and DH. The effect of composite genotypes on relative concentrations of the milk proteins was not as pronounced in DJ. The present work suggests that a higher frequency of BB/A(1)A(2)/AB, together with a decrease in BB/A(2)A(2)/AA, could have positive effects on DH and SR milk regarding, for example, the processing of cheese. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Associations of A-FABP and H-FABP markers with the content of intramuscular fat in Beijing-You chicken.

PubMed

Ye, M H; Chen, J L; Zhao, G P; Zheng, M Q; Wen, J

2010-01-01

This study has assessed the association of single nucleotide polymorphisms (SNP) identified in the adipocyte fatty acid binding protein (A-FABP) and heart-type fatty acid binding protein (H-FABP) genes with the content of intramuscular fat (IMF) in a population of male Beijing-You chickens. A previously described SNP in the chicken A-FABP gene had a significant (P < 0.05) effect on IMF content. Chickens inheriting the homozygous BB genotype at A-FABP had a significantly higher content of IMF in thigh muscles and breast muscles than did those inheriting the AA and AB genotypes. A novel SNP, identified here, in the H-FABP gene was also significantly (P < 0.05) associated with IMF content in thigh and breast muscle. Chickens inheriting the genotypes of DD and CD had much higher content of IMF than those inheriting the homozygous genotype of CC. Markers at the A-FABP and H-FABP genes were associated with IMF content in the studied population. Chickens inheriting the BB genotype at A-FABP, along with the CD genotype at H-FABP, produced muscles with a much higher content of IMF when compared with all other genotypes. A weak interaction between A-FABP and H-FABP was detected (P < 0.09) for IMF content in the tested population. The statistical significance of interaction is tentative because of the limited number of observations for some genotypic combinations. Markers identified within the A-FABP and H-FABP genes are suitable for future use in identifying chickens with the genetic potential to produce more desirable muscle with higher IMF content, at least in the population of Beijing-You male chickens.

A Qualitative Study to Understand Nativity Differences in Breastfeeding Behaviors Among Middle-Class African American and African-Born Women.

PubMed

Fabiyi, Camille; Peacock, Nadine; Hebert-Beirne, Jennifer; Handler, Arden

2016-10-01

Objective To explore nativity differences and the role of attitudes, social norms, and behavioral control perceptions surrounding breastfeeding initiation and duration among middle-class African-American (AA) and African-born (AB) mothers in the US. Methods Semi-structured individual interviews were conducted with 20 middle-class AA and AB mothers in central Ohio from December 2012 to February 2013. Interview questions were developed based on the Theory of Planned Behavior (TPB). Interviews were analyzed for salient themes by TPB constructs. Differences in themes were examined by nativity status. Results All study participants had initiated breastfeeding or bottle-feeding with expressed breast milk, noting the benefits it conferred as well as the persuasive encouragement they received from others. Persistent encouragement was often cited as a factor for sustaining breastfeeding. More AA mothers had discontinued breastfeeding by the time of the interview, which was often attributed to health, lactation, and work challenges. Inconsistent support from health providers, dissuasive remarks from others, ambivalent breastfeeding attitudes, and diminished family support led some mothers to begin formula supplementation. Analysis of maternal narratives revealed nativity differences across sources of encouragement. Specifically, important sources of encouragement were health providers for AA mothers and family, friends, partners and culture for AB mothers. Only AB mothers expressed concerns about difficulty they encountered with breastfeeding due to the lack of proximal family support. Conclusions Findings reveal that both groups of mothers may be susceptible to unsupportive breastfeeding norms in the US and also highlight the need for intervention in health care settings and workplaces to improve AA women's breastfeeding rates.

Screen of Bacillus thuringiensis toxins for transgenic rice to control Sesamia inferens and Chilo suppressalis.

PubMed

Gao, Yulin; Hu, Yang; Fu, Qiang; Zhang, Jie; Oppert, Brenda; Lai, Fengxiang; Peng, Yufa; Zhang, Zhitao

2010-09-01

Transgenic rice to control stem borer damage is under development in China. To assess the potential of Bacillus thuringiensis (Bt) transgenes in stem borer control, the toxicity of five Bt protoxins (Cry1Aa, Cry1Ab, Cry1Ac, Cry1Ba and Cry1Ca) against two rice stem borers, Sesamia inferens (pink stem borer) and Chilo suppressalis (striped stem borer), was evaluated in the laboratory by feeding neonate larvae on artificial diets containing Bt protoxins. The results indicated that Cry1Ca exhibited the highest level of toxicity to both stem borers, with an LC(50) of 0.24 and 0.30 microg/g for C. suppressalis and S. inferens, respectively. However, S. inferens was 4-fold lower in susceptibility to Cry1Aa, and 6- and 47-fold less susceptible to Cry1Ab and Cry1Ba, respectively, compared to C. suppressalis. To evaluate interactions among Bt protoxins in stem borer larvae, toxicity assays were performed with mixtures of Cry1Aa/Cry1Ab, Cry1Aa/Cry1Ca, Cry1Ac/Cry1Ca, Cry1Ac/Cry1Ba, Cry1Ab/Cry1Ac, Cry1Ab/Cry1Ba, and Cry1Ab/Cry1Ca at 1:1 (w/w) ratios. All protoxin mixtures demonstrated significant synergistic toxicity activity against C. suppressalis, with values of 1.6- to 11-fold higher toxicity than the theoretical additive effect. Surprisingly, all but one of the Bt protoxin mixtures were antagonistic in toxicity to S. inferens. In mortality-time response experiments, S. inferens demonstrated increased tolerance to Cry1Ab and Cry1Ac compared to C. suppressalis when treated with low or high protoxin concentrations. The data indicate the utility of Cry1Ca protoxin and a Cry1Ac/Cry1Ca mixture to control both stem borer populations. Copyright 2010 Elsevier Inc. All rights reserved.

Voltage-Gated Na+ Channel Isoforms and Their mRNA Expression Levels and Protein Abundance in Three Electric Organs and the Skeletal Muscle of the Electric Eel Electrophorus electricus

PubMed Central

Hiong, Kum C.; Boo, Mel V.; Wong, Wai P.; Chew, Shit F.

2016-01-01

This study aimed to obtain the coding cDNA sequences of voltage-gated Na+ channel (scn) α-subunit (scna) and β-subunit (scnb) isoforms from, and to quantify their transcript levels in, the main electric organ (EO), Hunter’s EO, Sach’s EO and the skeletal muscle (SM) of the electric eel, Electrophorus electricus, which can generate both high and low voltage electric organ discharges (EODs). The full coding sequences of two scna (scn4aa and scn4ab) and three scnb (scn1b, scn2b and scn4b) were identified for the first time (except scn4aa) in E. electricus. In adult fish, the scn4aa transcript level was the highest in the main EO and the lowest in the Sach’s EO, indicating that it might play an important role in generating high voltage EODs. For scn4ab/Scn4ab, the transcript and protein levels were unexpectedly high in the EOs, with expression levels in the main EO and the Hunter’s EO comparable to those of scn4aa. As the key domains affecting the properties of the channel were mostly conserved between Scn4aa and Scn4ab, Scn4ab might play a role in electrogenesis. Concerning scnb, the transcript level of scn4b was much higher than those of scn1b and scn2b in the EOs and the SM. While the transcript level of scn4b was the highest in the main EO, protein abundance of Scn4b was the highest in the SM. Taken together, it is unlikely that Scna could function independently to generate EODs in the EOs as previously suggested. It is probable that different combinations of Scn4aa/Scn4ab and various Scnb isoforms in the three EOs account for the differences in EODs produced in E. electricus. In general, the transcript levels of various scn isoforms in the EOs and the SM were much higher in adult than in juvenile, and the three EOs of the juvenile fish could be functionally indistinct. PMID:27907137

[Liver cirrhosis patogenetics: polymorphism of glutation S-transferase genes].

PubMed

Goncharova, I A; Rachkovskiĭ, M I; Beloborodova, E V; Gamal' Abd El'-Aziz Nasar, Kh; Puzyrev, V P

2010-01-01

Association of deletion polymorphism in GSTT1 and GSTM1 genes and polymorphic variant A313G of GSTP1 gene with cirrhosis diseases and 4-year survival rate for the Tomsk region (West Siberia) patients were tested. Homozygous deletion of GSTM1 gene (null genotype) was a protective factor for alcoholic and mixed (HCV, HBV and alcohol) liver cirrhosis development. The patients from the joint group (all etiology forms) as well as having alcoholic and mixed cirrhosis had lower frequency of GSTM1 null genotype (39.2, 39.0, and 34.2%, respectively) in comparison with the control group (64.6%). The GSTM1 null genotype and GSTP1 gene A313G polymorphic variant correlated with the patients' survival rate. The patients survived in comparison with the dead had higher frequency of a GSTM1 null genotype (46.6 vs. 30.2%) and GSTP1 AA genotype (63.1 vs. 40.5%), and lower frequency of GSTP1 AG (A313G) genotype (31.1 vs. 51.2%). A survival rate was 2.5 times higher for patients having GSTP1 AA genotype in comparison with the GG and AG genotype carriers and 2 times higher for patients having GSTM1 null genotype than the gene carriers. A 4-year fatal case probability was 2.3 times higher among the patients having heterozygous AG GSTP1 genotype in comparison with homozygous AA and GG genotype carriers.

CASPASE-12 and rheumatoid arthritis in African-Americans

PubMed Central

Marshall, Laura; Obaidullah, Mohammad; Fuchs, Trista; Fineberg, Naomi S.; Brinkley, Garland; Mikuls, Ted R.; Bridges, S. Louis; Hermel, Evan

2014-01-01

CASPASE-12 (CASP12) has a down-regulatory function during infection, and thus may protect against inflammatory disease. We investigated the distribution of CASP12 alleles (#rs497116) in African-Americans (AA) with rheumatoid arthritis (RA). CASP12 alleles were genotyped in 953 RA patients and 342 controls. Statistical analyses comparing genotype groups were performed using Kruskal-Wallis non-parametric ANOVA with Mann-Whitney U tests and chi-square tests. There was no significant difference in the overall distribution of CASP12 genotypes within AA with RA, but CASP12 homozygous patients had lower baseline joint narrowing scores. CASP12 homozygosity appears to be a subtle protective factor for some aspects of RA in AA patients. PMID:24515649

Tumor necrosis factor-α promoter -308/238 polymorphism association with less severe disease in ankylosing spondylitis is unrelated to serum TNF-α and does not predict TNF inhibitor response.

PubMed

Nossent, Johannes C; Sagen-Johnsen, Sylvia; Bakland, Gunnstein

2014-08-01

Despite the clinical efficacy of tumor necrosis factor inhibitors (TNFi), the manner in which TNF-α contributes to disease in patients with ankylosing spondylitis (AS) remains unresolved. We investigated the relationship between TNF-α gene promoter region polymorphism, serum TNF-α levels, and clinical phenotype. We did a cross-sectional and longitudinal cohort study in TNFi-naive patients with AS (n = 335). Clinical data and biological samples were collected during a research visit with genotyping for TNF-α -238 A/G and -308 A/G performed by Taqman RT-PCR and TNF levels determined by sandwich ELISA. Longitudinal TNF levels were monitored in unselected patients (n = 61). TNF-α -308 GA/AA genotype was present in 14% and TNF-α -238 GA/AA genotype in 1% of patients. TNF-α -308 GA/AA genotype was associated with a reduced risk of uveitis and better spinal function, while TNF-α -238 GA/AA genotype was associated with later age of onset and lower erythrocyte sedimentation rate (ESR). Serum TNF-α level was lower in patients with AS (151 pg/ml) than in controls (263 pg/ml), because more patients with AS had undetectable serum TNF-α (66 vs 25%, p < 0.001). TNFi treatment did not influence serum TNF-α. There was no effect of TNF-α -308/-238 or HLA-B27 genotype on serum TNF-α or subsequent initiation of TNFi. TNF-α -238 or -308 GA/AA genotypes in patients with AS are associated with signs of less severe disease. Serum TNF-α is, however, undetectable in two-thirds of patients with AS and is not influenced by TNF-α promoter genotype or TNFi therapy. These data suggest a more significant role for TNF-α at local sites of inflammation in AS than through systemic effects.

Phylogenetic analysis of the haemagglutinin gene of canine distemper virus strains detected from breeding foxes, raccoon dogs and minks in China.

PubMed

Zhao, Jian-Jun; Yan, Xi-Jun; Chai, Xiu-Li; Martella, Vito; Luo, Guo-Liang; Zhang, Hai-Ling; Gao, Han; Liu, Ying-Xue; Bai, Xue; Zhang, Lei; Chen, Tao; Xu, Lei; Zhao, Chun-Fei; Wang, Feng-Xue; Shao, Xi-Qun; Wu, Wei; Cheng, Shi-Peng

2010-01-06

Canine distemper virus (CDV) infects a variety of carnivores, including wild and domestic Canidae. Genetic/antigenic heterogeneity has been observed among the various CDV strains, notably in the haemagglutinin (H) gene, that appears as a good target to gather epidemiological information. Based on sequence analysis of the H gene, wild-type CDV strains cluster into distinct geographic lineages (genotypes), irrespective of the species of isolation. The sequence of the H gene of 28 CDV strains detected from both vaccinated and non-vaccinated breeding foxes, raccoon dogs and minks from different geographical areas of China during the years 2004-2008 was determined. All the CDV strains but two (strains HL and HLJ2) were characterized as Asia-1 genotype and were highly similar to each other (96.2-99.7% at the amino acid [aa] level) and to other Asia-1 strains (96.1-99.5% aa) previously detected in China. The CDV strains HL and HLJ2 were both collected from foxes in Heilongjiang province in 2005. Strain HL resembled CDVs of the Arctic genotype (GR88-like) and displayed high aa identity (98.0%) to the Chinese canine strain Liu. By converse, strain HLJ2 was barely related to CDVs of the Asia-2 genotype (88.7-90.3% aa identity), and could represent a novel CDV genotype, tentatively proposed as Asia-3. These results suggest that at least three different CDV genotypes, distantly related (81.8-91.6% aa identity) to the vaccine strains, Onderstepoort-like (America-1 genotype), are currently circulating in breeding foxes, raccoon dogs and minks in China, and that the genotype Asia-1 is predominant. Whether the diversity between wild-type CDVs and the vaccine strains may affect, to some extent, the efficacy of the vaccines deserves further investigations.

[The preliminary analysis of the recognition epitopes of anti-HEV monoclonal antibodies on HEV ORF2].

PubMed

Xiong, Jun-Hui; Guo, Qing-Shun; Ge, Sheng-Xiang; Gu, Ying; Chen, Yi-Xin; Miao, Ji; Du, Hai-Lian; Shi, Wei-Guo; Zhang, Jun; Xia, Ning-Shao

2008-06-01

Western blot, capture-PCR, blocking ELISA and synthetic polypeptides were used to systematically study the recognition epitopes on HEV ORF2 of 23 anti-HEV monoclonal antibodies(McAbs) which were previously generated in our laboratory directed against HEV ORF2. Results showed that seven McAbs recognized linear epitopes that located at aa408-458 of HEV ORF2 and 16 conformation-dependent McAbs, most of which recognized the surface epitopes of native HEV, located at aa459-606 of HEV ORF2. The systematical study of the recognition epitopes of anti-HEV McAbs on HEV ORF2 provides important information for the investigation of virus receptor and HEV infection mechanism, as well as its vaccine and diagnostics development.

Effects of mannose-binding lectin polymorphisms on irinotecan-induced febrile neutropenia.

PubMed

van der Bol, Jessica M; de Jong, Floris A; van Schaik, Ron H; Sparreboom, Alex; van Fessem, Marianne A; van de Geijn, Fleur E; van Daele, Paul L; Verweij, Jaap; Sleijfer, Stefan; Mathijssen, Ron H

2010-01-01

Mannose-binding lectin (MBL) is important in the innate immune response. MBL2 gene polymorphisms affect MBL expression, and genotypes yielding low MBL levels have been associated with an elevated risk for infections in hematological cancer patients undergoing chemotherapy. However, these reported associations are inconsistent, and data on patients with solid tumors are lacking. Here, we investigated the effects of MBL2 genotypes on irinotecan-induced febrile neutropenia in patients with solid tumors. Irinotecan-treated patients were genotyped for the MBL2 gene. Two promoter (-550 H/L and -221 X/Y) and three exon polymorphisms (52 A/D, 54 A/B, and 57 A/C) were determined, together with known risk factors for irinotecan-induced toxicity. Neutropenia and febrile neutropenia were recorded during the first course. Of the 133 patients, 28% experienced severe neutropenia and 10% experienced febrile neutropenia. No associations were found between exon polymorphisms and febrile neutropenia. However, patients with the H/H promoter genotype, associated with high MBL levels, experienced significantly more febrile neutropenia than patients with the H/L and L/L genotypes (20% versus 13% versus 5%). Moreover, patients with the HYA haplotype encountered significantly more febrile neutropenia than patients without this high MBL-producing haplotype (16% versus 4%). In the subgroup with wild-type exon polymorphisms (A/A), patients with the high MBL promoter phenotype had the highest incidence of febrile neutropenia, regardless of known risk factors. Patients with high MBL2 promoter genotypes and haplotypes seem more at risk for developing febrile neutropenia. If confirmed, these preliminary findings may contribute to more individualized approaches of irinotecan treatment.

GATA3 rs3824662 gene polymorphism as possible risk factor in a cohort of Egyptian patients with pediatric acute lymphoblastic leukemia and its prognostic impact.

PubMed

Mosaad, Youssef M; Elashery, Rasha; Darwish, Ahmad; Sharaf Eldein, Omar A; Barakat, Tarek; Marouf, Samy; Abou El-Khier, Noha T; Youssef, Laila F; Fawzy, Iman M

2017-03-01

To investigate the possible role of GATA3 rs3824662 polymorphism as risk factor for the development of acute lymphoblastic leukemia (ALL) in a cohort of Egyptian children and to evaluate its prognostic role. Typing of GATA3 rs3824662 polymorphism was done using real-time PCR for 116 patients with ALL and 273 healthy controls. The A allele and AA genotype were significantly higher in ALL patients (p = .015 and .016, respectively) especially B-ALL (p = .014 and .01, respectively). The AA genotype was associated with shorter disease free survival (DFS) in univariate (p = .017) and multivariate cox regression analysis (p = .028), increased incidence of relapse (p = .008) and poor prognosis (p = .028) in pediatric ALL. The GATA3 rs3824662 A allele and AA genotype may be risk factors for the development of pediatric ALL especially B-ALL in the studied cohort of Egyptian patients. The AA genotype is associated with shorter DSF, increased incidence of relapse and poor prognosis in pediatric ALL.

The Association Between MCT1 T1470A Polymorphism and Power-Oriented Athletic Performance.

PubMed

Kikuchi, N; Fuku, N; Matsumoto, R; Matsumoto, S; Murakami, H; Miyachi, M; Nakazato, K

2017-01-01

The purpose of this study was to investigate the effects of the MCT1 T1470A polymorphism (rs1049434) on power-oriented performance and lactate concentration during or after cycling sprints in Japanese wrestlers. Participants (199 wrestlers and 649 controls) were genotyped for the MCT1 T1470A genotype (rs1049434) using the TaqMan ® Assay. All wrestlers were international (n=77) or national (n=122) level athletes. Among them, 46 wrestlers performed 2 anaerobic performance tests, a 30-s Wingate Anaerobic test (WAnT) and a series of 10 maximal effort 10-s sprints on a cycle ergometer. Blood lactate levels were measured before, during, and after the tests. In the A-allele recessive model (AA vs. TA+TT), the frequency of the AA genotype was significantly higher in all wrestlers than in controls (p=0.037). Wrestlers with AA genotype had lower blood lactate concentrations than those with TA+TT genotype at 10 min after the WAnT and following the 5 th and the final set of repeated cycling sprints (p<0.05). The AA genotype of the MCT1 T1470A polymorphism is over-represented in wrestlers compared with controls and is associated with lower blood lactate concentrations after 30-s WAnT and during intermittent sprint tests in Japanese wrestlers. © Georg Thieme Verlag KG Stuttgart · New York.

Genetic polymorphisms within exon 3 of heat shock protein 90AA1 gene and its association with heat tolerance traits in Sahiwal cows

PubMed Central

Kumar, Rakesh; Gupta, I. D.; Verma, Archana; Verma, Nishant; Vineeth, M. R.

2015-01-01

Aim: The present study was undertaken to identify novel single nucleotide polymorphism (SNP) in Exon 3 of HSP90AA1 gene and to analyze their association with respiration rate (RR) and rectal temperature (RT) in Sahiwal cows. Materials and Methods: The present study was carried out in Sahiwal cows (n=100) with the objectives to identify novel SNP in exon 3 of HSP90AA1 gene and to explore the association with heat tolerance traits. CLUSTAL-W multiple sequence analysis was used to identify novel SNPs in exon 3 of HSP90AA1 gene in Sahiwal cows. Gene and genotype frequencies of different genotypes were estimated by standard procedure POPGENE version 1.32 (University of Alberta, Canada). The significant effect of SNP variants on physiological parameters, e.g. RR and RT were analyzed using the General Linear model procedure of SAS Version 9.2. Results: The polymerase chain reaction product with the amplicon size of 450 bp was successfully amplified, covering exon 3 region of HSP90AA1 gene in Sahiwal cows. On the basis of comparative sequence analysis of Sahiwal samples (n=100), transitional mutations were detected at locus A1209G as compared to Bos taurus (NCBI GenBank AC_000178.1). After chromatogram analysis, three genotypes AA, AG, and GG with respective frequencies of 0.23, 0.50, and 0.27 ascertained. RR and RT were recorded once during probable extreme hours in winter, spring, and summer seasons. It was revealed that significant difference (p<0.01) among genetic variants of HSP90AA1 gene with heat tolerance trait was found in Sahiwal cattle. The homozygotic animals with AA genotype had lower heat tolerance coefficient (HTC) (1.78±0.04a), as compared to both AG and GG genotypes (1.85±0.03b and 1.91±0.02c), respectively. The gene and genotype frequencies for the locus A1209G were ascertained. Conclusions: Novel SNP was found at the A1209G position showed all possible three genotypes (homozygous and heterozygous). Temperature humidity index has a highly significant association with RR, RT, and HTC in all the seasons. Perusal of results across different seasons showed the significant (p<0.01) difference in RR, RT, and HTC among winter, spring, and summer seasons. Genetic association with heat tolerance traits reveals their importance as a potential genetic marker for heat tolerance traits in Sahiwal cows. PMID:27047179

Antioxidant Bioactive Compounds Changes in Fruit of Quince Genotypes Over Cold Storage.

PubMed

Moradi, Samira; Koushesh Saba, Mahmoud; Mozafari, Ali Akbar; Abdollahi, Hamid

2016-07-01

Quince fruit has many benefits to human health and is excellent source of bioactive compounds. The fruit of 15 quince genotypes stored at 2 °C for 5 mo to study fruit quality changes during cold storage. Fruit were sampled monthly and stored at 20 °C for 24 h. Fruit ascorbic acid (AA), total phenol (TP), and total flavonoid (TF) concentrations, total antioxidant activity (TAA), flesh browning (FB) incidence, polyphenol oxidase (PPO), peroxidase (POX), and superoxide dismutase (SOD) activities were measured during storage. A high variation in bioactive compounds was observed across genotypes. The range of 26.8 to 44.4 mg/100 g FW for AA, 86.7% to 98.2% for TAA, 157.7 to 380.7 mg GAE 100(-1) g FW for TP, and 5.3 to 10.7 mg/100 g FW for TF were observed across genotypes at harvest time. The overall AA, TAA, TP, TF, and SOD decreased while PPO and POX increased during storage. FB was first observed after 4 mo and increased thereafter while the FB index was different across genotypes. Higher bioactive content may prevent or reduce FB index so that a negative correlation was found between FB and AA, TAA, TP, TF, and SOD. © 2016 Institute of Food Technologists®

Omentin Polymorphism and its Relations to Bone Mineral Density in Women.

PubMed

Boron, Dariusz; Czerny, Boguslaw; Bartkowiak-Wieczorek, Joanna; Sieron, Dominik; Wolski, Hubert

2015-04-01

Recognition of different genetic variants underlying development of osteoporosis would make it possible to administer individual symptomatic treatment as well as early prophylactics of osteoporosis. The aim of the study was to evaluate frequency of polymorphism 326A/T of gene ITLN-1 and assessment of its relations with the clinical parameters of osseous turnover and degree of postmenopausal osteoporosis. The study included 800 women at the postmenopausal (505) and reproductive (295) age throughout Wielkopolska region in Poland. The postmenopausal group included women with osteoporosis and osteopenia and the healthy ones. Women at the reproductive age were healthy. Frequency of the tested gene polymorphism was evaluated in the group where BMD was marked and in the control group. The analysis of the polymorphism A326T of gene ITLN-1 showed that in healthy postmenopausal female with genotype AA birth weight, BMD L2-L4 YA (%) and BMD L2-L4 AM (%) were significantly higher (BMD-bone mineral density; L2-L4-- lumbar vertebrae no 2, 4; YA--peak adult bone mass; AM--age-matched bone mass). In women with osteopenia BMD L2-L4 YA (%) and BMD L2-L4 AM (%) were significantly higher in women with genotype AA, but BMD L2-L4 was significantly higher in women with genotype TT. In women with osteoporosis with genotype AA T-score was significantly higher, but BMD L2-L4 and BMD L2-L4 YA (%) were significantly lower in this group. BMD L2-L4 AM (%) was significantly higher in women with AA genotype. In women with osteoporosis and osteopenia homozygous AA genotype may predispose to lower BMD in the lumbar spine. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

Associations of TNF-α -238 A/G and IL-10 -1082 G/A Genetic Polymorphisms With the Risk of NONFH in the Chinese Population.

PubMed

Wei, Biao-Fang; Feng, Zhi; Wei, Wei; Chen, Xiao

2017-12-01

The study aims to explore the roles of common polymorphisms of Tumor Necrosis Factor-α (TNF-α) (-238 A/G and -308 A/G) and IL-10 (-819 T/C and -1082 G/A) genes in the risk of non-traumatic osteonecrosis of the femoral head (NONFH). One hundred and forty-seven NONFH patients and 135 healthy individuals were selected as the case and control groups. qRT-PCR and Western blotting techniques detected mRNA as well as protein expressions of TNF-α and IL-10 of each genotype in both the case and control groups. The GA genotype and the A allele of TNF-α -238 A/G were higher in the case group than in the control group. Compared with the control group, AA, GA, and AG + AA genotypes as well as the A allele of IL-10-1082 G/A were all lower in the case group. In the case groups increased levels of TNF-α as well as decreased levels of IL-10 expression when compared with the control group. TNF-α expression of TNF-α-238 GA genotype was significantly higher than that in patients with GG genotype, while the IL-10 expression of GA and AA genotypes of IL-10-1082 was significantly lower than in that of patients with the GG genotype. TNF-α protein expression in the GA genotype was significantly higher than in the GG genotype. In relation to TNF-α -238, TNF-α protein expression of GA and AA genotypes had significantly reduced more so than the GG genotype in IL-10-1082. TNF-α-238 A/G and IL-10-1082 G/A may be involved as risk factors of NONFH. J. Cell. Biochem. 118: 4872-4880, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

On Mass Polarization Effect in Three-Body Nuclear Systems

NASA Astrophysics Data System (ADS)

Filikhin, I.; Kezerashvili, R. Ya.; Suslov, V. M.; Vlahovic, B.

2018-05-01

The mass polarization effect is considered for different three-body nuclear AAB systems having a strongly bound AB and unbound AA subsystems. We employ the Faddeev equations for calculations and the Schrödinger equation for analysis of the contribution of the mass polarization term of the kinetic-energy operator. For a three-boson system the mass polarization effect is determined by the difference of the doubled binding energy of the AB subsystem 2E2 and the three-body binding energy E3(V_{AA}=0) when the interaction between the identical particles is omitted. In this case: | E3(V_{AA}=0)| >2| E2| . In the case of a system complicated by isospins(spins), such as the kaonic clusters K-K-p and ppK-, a similar evaluation is impossible. For these systems it is found that | E3(V_{AA}=0)| <2| E2| . A model with an AB potential averaged over spin(isospin) variables transforms the latter case to the first one. The mass polarization effect calculated within this model is essential for the kaonic clusters. In addition we have obtained the relation |E_3|≤|2E_2| for the binding energy of the kaonic clusters.

Correlational studies on insulin resistance and leptin gene polymorphisms in peritoneal dialysis patients

PubMed Central

Cao, Liou; Mou, Shan; Fang, Wei; Qi, Chaojun; Chang, Xinbei; Gu, Leyi; Qian, Jiaqi; Ni, Zhaohui

2015-01-01

Objective(s): The aim of the study was to investigate the relationship between insulin resistance (IR) and leptin (LEP) gene polymorphisms in peritoneal dialysis (PD) patients. Materials and Methods: From July 1, 2011 to August 1, 2011, patients who received chronic PD were chosen and divided into three groups (DM, high HOMR-IR, and low HOMR-IR). Two PCR products of LEP were sequenced and aligned and the distribution of polymorphisms was analyzed using χ2 analysis. In addition, serum leptin level, PD conditions, and biochemical parameters according to different genotype of G-2548A and A19G were statistically analyzed (P-value<0.05). The relationship between LEP gene polymorphisms and prognosis was explored. Results: Totally 157 patients with average age of 55±15 years old were chosen. Distribution of genotype frequencies was complied with Hardy-Weinberg equilibrium. Leptin level and BMI (body mass index) of the GG genotype of G-2548A were higher than that of GA or AA. The fasting glucose, cholesterol, etc. of AA genotype were lower, and the nPCR was higher than the two other genotypes. Serum leptin level and BMI of AA genotype of A19G was higher than GA and GG genotypes; meanwhile, fasting blood glucose of that genotypes was the highest. In addition, survival rate of AA group of A19G was very low. Conclusion: The G-2548A and A19G polymorphisms were correlated with serum leptin level and IR. Leptin A19G polymorphism may be prognostic for PD patients. This study may facilitate early intervention for IR in PD patients. PMID:26523220

Functional characterisation of a SNP in the ABCC11 allele - effects on axillary skin metabolism, odour generation and associated behaviours.

PubMed

Harker, Mark; Carvell, Ann-Marie; Marti, Vernon P J; Riazanskaia, Svetlana; Kelso, Hailey; Taylor, David; Grimshaw, Sally; Arnold, David S; Zillmer, Ruediger; Shaw, Jane; Kirk, Jayne M; Alcasid, Zee M; Gonzales-Tanon, Sheila; Chan, Gertrude P; Rosing, Egge A E; Smith, Adrian M

2014-01-01

A single nucleotide polymorphism (SNP), 538G→A, leading to a G180R substitution in the ABCC11 gene results in reduced concentrations of apocrine derived axillary odour precursors. Determine the axillary odour levels in the SNP ABCC11 genotype variants and to investigate if other parameters associated with odour production are affected. Axillary odour was assessed by subjective quantification and gas chromatography headspace analysis. Metabolite profiles, microbiome diversity and personal hygiene habits were also assessed. Axillary odour in the A/A homozygotes was significantly lower compared to the G/A and G/G genotypes. However, the perception-based measures still detected appreciable levels of axillary odour in the A/A subjects. Metabolomic analysis highlighted significant differences in axillary skin metabolites between A/A subjects compared to those carrying the G allele. These differences resulted in A/A subjects lacking specific volatile odourants in the axillary headspace, but all genotypes produced odoriferous short chain fatty acids. Microbiomic analysis revealed differences in the relative abundance of key bacterial genera associated with odour generation between the different genotypes. Deodorant usage indicated a high level of self awareness of axillary odour levels with A/A individuals less likely to adopt personal hygiene habits designed to eradicate/mask its presence. The SNP in the ABCC11 gene results in lower levels of axillary odour in the A/A homozygotes compared to those carrying the G allele, but A/A subjects still produce noticeable amounts of axillary odour. Differences in axillary skin metabolites, bacterial genera and personal hygiene behaviours also appear to be influenced by this SNP. Copyright © 2013. Published by Elsevier Ireland Ltd.

MMP-8 genotypes influence the inflammatory response in human endotoxemia.

PubMed

Rella, Judith M; Jilma, Bernd; Fabry, Astrid; Kaynar, A Murat; Mayr, Florian B

2014-04-01

Clinical studies have reported associations between MMP-8 genotypes and clinical outcomes without exploring underlying mechanisms. This study aims to understand the influence of the rs1940475 SNP on downstream chemokine and cytokine response in human endotoxemia. Rs1940475 was genotyped in 44 healthy Caucasian males, who were challenged with an intravenous bolus of 2 ng/kg lipopolysaccharide (LPS). Plasma levels of tumor necrosis factor (TNF), interleukin (IL)-6, IL-8, and macrophage inflammatory protein (MIP)-1α were measured at baseline and 2, 4, 6, and 24 h after LPS infusion with high-sensitivity enzyme immunoassays. Peak TNF levels at 2 h after LPS infusion were significantly higher in subjects with AA genotype compared to subjects with AG or GG genotypes (185 pg/mL [IQR, 154-234] vs. 94 pg/mL [IQR, 65-125] vs. 107 pg/mL [IQR, 80-241], respectively; p = 0.03 between groups). Peak IL-6 levels were trend-wise higher in subjects with AA genotype compared to those with AG or GG genotypes (566 pg/mL [IQR, 294-644] vs. 278 pg/mL [IQR, 184-539] and 329 pg/mL [IQR, 240-492], respectively; p = 0.15 between groups). In contrast, peak MIP-1α at 2 h was highest in GG genotype carriers compared to those with AG or AA genotypes (602 pg/mL [IQR, 449-727] vs. 389 pg/mL [IQR, 375-490] and 510 pg/mL [425-813], respectively; p < 0.03 between groups). AA genotype carriers had highest peak TNF and IL-6 levels after LPS challenge, whereas peak MIP-1α levels were highest in GG carriers. This indicates that the rs1940475 SNP modifies the host response to inflammatory stimuli, which may in part explain previously shown associations with clinical outcomes.

Genotypic to expression profiling of bovine calcium channel, voltage-dependent, alpha-2/delta subunit 1 gene, and their association with bovine mastitis among Frieswal (HFX Sahiwal) crossbred cattle of Indian origin.

PubMed

Deb, Rajib; Singh, Umesh; Kumar, Sushil; Kumar, Arun; Singh, Rani; Sengar, Gyanendra; Mann, Sandeep; Sharma, Arjava

2014-04-03

Calcium channel, voltage-dependent, alpha-2/delta subunit 1 (CACNA2D1) gene is considered to be an important noncytokine candidate gene influencing mastitis. Scanty of reports are available until today regarding the role play of CACNA2D1 gene on the susceptibility of bovine mastitis. We interrogated the CACNA2D1 G519663A [A>G] SNP by PCR-RFLP among two hundreds Frieswal (HF X Sahiwal) crossbred cattle of Indian origin. Genotypic frequency of AA (51.5, n=101) was comparatively higher than AG (35, n=70) and GG (14.5, n=29). Association of Somatic cell score (SCS) with genotypes revealed that, GG genotypes showing lesser count (less susceptible to mastitis) compare to AA and AG. Relative expression of CACNA2D1 transcript (in milk samples) was significantly higher among GG than AG and AA. Further we have also isolated blood sample from the all groups and PBMCs were cultured from each blood sample as per the standard protocol. They were treated with Calcium channel blocker and the expression level of the CACNA2D1 gene was evaluated by Real Time PCR. Results show that expression level decline in each genotypic group after treatment and expression level of GG are again significantly higher than AA and AG. Thus, it may be concluded that GG genotypic animals are favorable for selecting disease resistant breeds.

Topological Quantum Phase Transitions in Two-Dimensional Hexagonal Lattice Bilayers

NASA Astrophysics Data System (ADS)

Zhai, Xuechao; Jin, Guojun

2013-09-01

Since the successful fabrication of graphene, two-dimensional hexagonal lattice structures have become a research hotspot in condensed matter physics. In this short review, we theoretically focus on discussing the possible realization of a topological insulator (TI) phase in systems of graphene bilayer (GBL) and boron nitride bilayer (BNBL), whose band structures can be experimentally modulated by an interlayer bias voltage. Under the bias, a band gap can be opened in AB-stacked GBL but is still closed in AA-stacked GBL and significantly reduced in AA- or AB-stacked BNBL. In the presence of spin-orbit couplings (SOCs), further demonstrations indicate whether the topological quantum phase transition can be realized strongly depends on the stacking orders and symmetries of structures. It is observed that a bulk band gap can be first closed and then reopened when the Rashba SOC increases for gated AB-stacked GBL or when the intrinsic SOC increases for gated AA-stacked BNBL. This gives a distinct signal for a topological quantum phase transition, which is further characterized by a jump of the ℤ2 topological invariant. At fixed SOCs, the TI phase can be well switched by the interlayer bias and the phase boundaries are precisely determined. For AA-stacked GBL and AB-stacked BNBL, no strong TI phase exists, regardless of the strength of the intrinsic or Rashba SOCs. At last, a brief overview is given on other two-dimensional hexagonal materials including silicene and molybdenum disulfide bilayers.

Race moderates the association of Catechol-O-methyltransferase genotype and posttraumatic stress disorder in preschool children.

PubMed

Humphreys, Kathryn L; Scheeringa, Michael S; Drury, Stacy S

2014-10-01

The present study sought to replicate previous findings of an association between the Catechol-O-methyltransferase (COMT) val158met polymorphism with posttraumatic stress disorder (PTSD) and symptomatology in a novel age group, preschool children. COMT genotype was determined in a sample of 171 3-6-year-old trauma-exposed children. PTSD was assessed with a semistructured interview. Accounting for sex, trauma type, and age, genotype was examined in relation to categorical and continuous measures of PTSD both controlling for race and within the two largest racial categories (African American [AA] and European American [EA]). Race significantly moderated the association between genotype and PTSD. Specifically, the genotype associated with increased PTSD symptoms in one racial group had the opposite association in the other racial group. For AA children the met/met genotype was associated with more PTSD symptoms. However, for EA children, val allele carriers had more PTSD symptoms. Whereas every AA child with the met/met genotype met criteria for PTSD, none of the EA children with the met/met genotype did. This genetic association with COMT genotype, in both races but in opposite directions, was most associated with increased arousal symptoms. These findings replicate previous findings in participants of African descent, highlight the moderating effect of race on the association between COMT genotype and PTSD, and provide direct evidence that consideration of population stratification within gene-by-environment studies is valuable to prevent false negative findings.

Race Moderates the Association of Catechol-O-methyltransferase Genotype and Posttraumatic Stress Disorder in Preschool Children

PubMed Central

Humphreys, Kathryn L.; Scheeringa, Michael S.

2014-01-01

Abstract Objective: The present study sought to replicate previous findings of an association between the Catechol-O-methyltransferase (COMT) val158met polymorphism with posttraumatic stress disorder (PTSD) and symptomatology in a novel age group, preschool children. Methods: COMT genotype was determined in a sample of 171 3–6-year-old trauma-exposed children. PTSD was assessed with a semistructured interview. Accounting for sex, trauma type, and age, genotype was examined in relation to categorical and continuous measures of PTSD both controlling for race and within the two largest racial categories (African American [AA] and European American [EA]). Results: Race significantly moderated the association between genotype and PTSD. Specifically, the genotype associated with increased PTSD symptoms in one racial group had the opposite association in the other racial group. For AA children the met/met genotype was associated with more PTSD symptoms. However, for EA children, val allele carriers had more PTSD symptoms. Whereas every AA child with the met/met genotype met criteria for PTSD, none of the EA children with the met/met genotype did. This genetic association with COMT genotype, in both races but in opposite directions, was most associated with increased arousal symptoms. Conclusions: These findings replicate previous findings in participants of African descent, highlight the moderating effect of race on the association between COMT genotype and PTSD, and provide direct evidence that consideration of population stratification within gene-by-environment studies is valuable to prevent false negative findings. PMID:25329975

Common allelic variants of the vitamin receptor D gene rs7975232 (ApaI) do not influence bone mineral density figures in postmenopausal osteoporotic women.

PubMed

Pedrera-Canal, Maria; Moran, Jose M; Vera, Vicente; Roncero-Martin, Raul; Lavado-Garcia, Jesus M; Aliaga, Ignacio; Pedrera-Zamorano, Juan D

2015-01-01

This study examined the association between bone mineral density (BMD) and the rs7975232 (ApaI) polymorphism of the vitamin receptor D (VDR) gene. The polymorphism was detected using the real-time PCR TaqMan method. The rs7975232 genotype was determined in 274 postmenopausal osteoporotic Spanish women who were 60.53±8.02 years old. The observed genotype frequencies were in agreement with Hardy-Weinberg equilibrium (χ(2)=1.85, P=0.1736). There were no significant differences in the rs7975232 genotype groups in our total sample of osteoporotic women regarding age, years since menopause, height, weight, and BMD at femoral neck, femoral trochanter and lumbar spine. Significant differences were found in menarche age (aa vs Aa; P=0.008) and BMI (aa vs AA; P=0.029). We conclude that the VDR gene rs7975232 polymorphism is not related to figures of bone mineral density in postmenopausal osteoporotic Spanish women.

Vitamin D receptor gene polymorphism in Egyptian pediatric acute lymphoblastic leukemia correlation with BMD.

PubMed

Tantawy, Maha; Amer, Mahmoud; Raafat, Tarek; Hamdy, Nayera

2016-09-01

We studied the frequencies of the 3' and 5'-end vitamin D receptor (VDR) gene polymorphisms and their correlation with bone mineral density (BMD) in Egyptian pediatric acute lymphoblastic leukemia (ALL) patients receiving calcium and vitamin D supplements. The purpose of this study is to find out the relation between VDR polymorphism and the response to vitamin D intake in pediatric ALL cases who receive corticosteroid therapy which predispose to osteoporosis. This study might shed the light on some genetic variants that are effect the response of individuals to vitamin D therapy. Forty newly diagnosed pediatrics ALL cases were studied. Three SNPs at the 3'-end of the VDR gene (BsmI rs1544410, ApaI rs739837and TaqI rs731236) and two SNPs at the 5'-end (Cdx-2 rs11568820 and GATA rs4516035) were analyzed by Allelic discrimination assay. Of those twenty-six cases with initial BMD data available were further analyzed with regards to the effect of various VDR genotypes/haplotypes on BMD. The genotype frequencies at 3'-end of VDR gene were, TaqI TT 23%, Tt 54% and tt 23%, BsmI bb 19.2%, Bb 65.4% and BB 15.4% and ApaI AA 12%, Aa 27% and aa 61%. The frequencies at the 5'-end were Cdx-2 GG 34.5%, GA 54% and AA 11.5% and GATA AA 8%, AG 50% and GG 42%. Eight and four possible haplotypes were observed at the 3' and 5'-ends of the VDR gene respectively. The Tt genotype was significantly correlated with high BMD as compared to other TaqI genotypes (P = 0.0420). There was a trend towards higher BMD with the genotype Bb as compared to other BsmI genotypes. No statistical significance was found between the other VDR genotypes or haplotypes studied and BMD. This is the first report on VDR gene polymorphisms in Egyptian pediatric ALL patients. The Tt genotype was associated with increased BMD. Our study showed marked genetic heterogeneity in VDR gene in Egyptian pediatric ALL patients.

Allelic Prevalence of ABO Blood Group Genes in Iranian Azari Population.

PubMed

Nojavan, Mohammad; Shamsasenjan, Karrim; Movassaghpour, Ali Akbar; Akbarzadehlaleh, Parvin; Torabi, Seyd Esmail; Ghojazadeh, Morteza

2012-01-01

ABO blood group system is the most important blood group in transfusion and has been widely used in population studies. Several molecular techniques for ABO allele's detection are widely used for distinguishing various alleles of glycosyl transferase locus on chromosome 9. 744 randomly selected samples from Azari donors of East Azerbaijan province (Iran) were examined using well-adjusted multiplex allele- specific PCR ABO genotyping technique. The results were consistent for all individuals. The ABO blood group genotype of 744 healthy Azari blood donors was: 25.8% AA/AO (2), 7.6% AO (1), 1.6% BB, 11.3% B0 (1), 10% AB, 9.3% 0(1)0(1) and 15.3%0(1)0(2). The highest genotype frequency belonged to O01/O02 genotype (15.3%) and the lowest frequency belonged to A101/A102 genotype (0.4%). The frequencies of ABO alleles didn't show significant differences between East Azerbaijan province population and that of other areas of the country. Meanwhile, statistical analysis of frequencies of A and B alleles between East Azerbaijan province population and neighbor countries showed significant differences whereas the frequency of allele O between them did not show significant difference (P>0.05). The frequencies of ABO alleles didn't show significant differences between East Azerbaijan province population and that of other areas of the country. Meanwhile, statistical analysis of frequencies of A and B alleles between East Azerbaijan province population and neighbor countries showed significant differences whereas the frequency of allele O between them did not show significant difference (P>0.05).

Genetic influences on right ventricular systolic pressure (RVSP) in chronic obstructive pulmonary disease (COPD).

PubMed

Shaw, Janet G; Dent, Annette G; Passmore, Linda H; Burstow, Darryl J; Bowman, Rayleen V; Zimmerman, Paul V; Fong, Kwun M; Yang, Ian A

2012-06-13

Pulmonary hypertension (PH) is a complication of chronic obstructive pulmonary disease (COPD). This study examined genetic variations in mediators of vascular remodelling and their association with PH in patients with COPD. In patients with COPD, we genotyped 7 SNPs in 6 candidate PH genes (NOS3, ACE, EDN1, PTGIS, SLC6A4, VEGFA). We tested for association with right ventricular systolic pressure (RVSP), spirometry and gas transfer, and hypoxemia. In patients with COPD, we genotyped 7 SNPs in 6 candidate PH genes (NOS3, ACE, EDN1, PTGIS, SLC6A4, VEGFA). We tested for association with right ventricular systolic pressure (RVSP), spirometry and gas transfer, and hypoxemia. 580 COPD patients were recruited, 341 patients had a transthoracic echocardiogram, with RVSP measurable in 278 patients (mean age 69  years, mean FEV1 50% predicted, mean RVSP 44  mmHg, median history of 50 pack-years). Of the 7 tested SNPs, the NOS3-VNTR polymorphism was significantly associated with RVSP in a dose-dependent fashion for the risk allele: mean RVSP for a/a and a/b genotypes were 52.0 and 46.6  mmHg respectively, compared to 43.2  mmHg for b/b genotypes (P = 0.032). No associations were found between RVSP and other polymorphisms. ACE II or ID genotypes were associated with a lower FEV1% predicted than the ACE DD genotype (P = 0.028). The NOS3-298 TT genotype was associated with lower KCO % predicted than the NOS3-298 GG or GT genotype (P = 0.031). The NOS3-VNTR polymorphism was associated with RVSP in patients with COPD, supporting its involvement in the pathogenesis of PH in COPD. ACE and NOS3 genotypes were associated with COPD disease severity, but not with the presence of PH. Further study of these genes could lead to the development of prognostic and screening tools for PH in COPD.

Effects of Mannose-Binding Lectin Polymorphisms on Irinotecan-Induced Febrile Neutropenia

PubMed Central

de Jong, Floris A.; van Schaik, Ron H.; Sparreboom, Alex; van Fessem, Marianne A.; van de Geijn, Fleur E.; van Daele, Paul L.; Verweij, Jaap; Sleijfer, Stefan; Mathijssen, Ron H.

2010-01-01

Objective. Mannose-binding lectin (MBL) is important in the innate immune response. MBL2 gene polymorphisms affect MBL expression, and genotypes yielding low MBL levels have been associated with an elevated risk for infections in hematological cancer patients undergoing chemotherapy. However, these reported associations are inconsistent, and data on patients with solid tumors are lacking. Here, we investigated the effects of MBL2 genotypes on irinotecan-induced febrile neutropenia in patients with solid tumors. Patients and Methods. Irinotecan-treated patients were genotyped for the MBL2 gene. Two promoter (−550 H/L and −221 X/Y) and three exon polymorphisms (52 A/D, 54 A/B, and 57 A/C) were determined, together with known risk factors for irinotecan-induced toxicity. Neutropenia and febrile neutropenia were recorded during the first course. Results. Of the 133 patients, 28% experienced severe neutropenia and 10% experienced febrile neutropenia. No associations were found between exon polymorphisms and febrile neutropenia. However, patients with the H/H promoter genotype, associated with high MBL levels, experienced significantly more febrile neutropenia than patients with the H/L and L/L genotypes (20% versus 13% versus 5%). Moreover, patients with the HYA haplotype encountered significantly more febrile neutropenia than patients without this high MBL-producing haplotype (16% versus 4%). In the subgroup with wild-type exon polymorphisms (A/A), patients with the high MBL promoter phenotype had the highest incidence of febrile neutropenia, regardless of known risk factors. Conclusion. Patients with high MBL2 promoter genotypes and haplotypes seem more at risk for developing febrile neutropenia. If confirmed, these preliminary findings may contribute to more individualized approaches of irinotecan treatment. PMID:20930093

Common Polymorphisms in GSTA1, GSTM1 and GSTT1 Are Associated with Susceptibility to Urinary Bladder Cancer in Individuals from Balkan Endemic Nephropathy Areas of Serbia.

PubMed

Matic, Marija; Dragicevic, Biljana; Pekmezovic, Tatjana; Suvakov, Sonja; Savic-Radojevic, Ana; Pljesa-Ercegovac, Marija; Dragicevic, Dejan; Smiljic, Jelena; Simic, Tatjana

2016-09-01

Balkan endemic nephropathy (BEN) is a chronic familial form of interstitial nephritis that might eventually lead to end stage renal disease. This nephropathy affects individuals living along of the Danube River and its tributaries in Serbia, Bosnia, Croatia, Bulgaria and Romania. The increased incidence of urinary tract tumors in the BEN areas is well described, but its specific genetic predisposition is still unclear. Certain nephrocarcinogenic compounds, including those associated with BEN, are metabolized by glutathione S-transferase (GST) superfamily of phase II detoxication enzymes. Importantly, the GST-mediated detoxification may result in formation of more toxic compounds. We examined the association of common GST polymorphisms and bladder cancer (BC) risk in individuals from BEN areas in Serbia. A hospital-based case-control study included 201 BC cases (67 from BEN region) and 122 controls. Each polymorphism was identified by a PCR-based method. Individuals from BEN region with low-expression GSTA1 genotype (AB+BB) exhibited a 2.6-fold higher BC risk compared to those with GSTA1 (AA) genotype who were from non-BEN region (OR = 2.60, p = 0.015). In contrast, carriers of GSTM1-active genotype from BEN region had a 2.9-fold increased BC risk compared to those with GSTM1-active genotype from non-BEN region (OR = 2.90, p = 0.010). Likewise, carriers with GSTT1-active genotype from BEN region exhibited 2.1-fold higher BC risk compared to those from non-BEN region with GSTT1-active genotype (OR = 2.10, p = 0.027). Thus, common polymorphisms in GSTA1, GSTM1 and GSTT1 are associated with susceptibility to BC in individuals from BEN areas of Serbia.

Interactions of a PPARGC1A Variant and a PNPLA3 Variant Affect Nonalcoholic Steatohepatitis in Severely Obese Taiwanese Patients.

PubMed

Tai, Chi-Ming; Huang, Chih-Kun; Tu, Hung-Pin; Hwang, Jau-Chung; Yeh, Ming-Lun; Huang, Chung-Feng; Huang, Jee-Fu; Dai, Chia-Yen; Chuang, Wan-Long; Yu, Ming-Lung

2016-03-01

The patatin-like phospholipase domain-containing protein 3 (PNPLA3) variant is associated with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). However, the role of genetic variations of the peroxisome proliferator-activated receptor gamma coactivator-1-alpha gene (PPARGC1A) and glucokinase regulatory (GCKR) gene on NASH in obese patients remains unclear. We studied the effects and interaction of these genetic polymorphisms on NASH in severely obese Taiwanese patients.The genotypes of PPARGC1A rs8192678, PNPLA3 rs738409, and GCKR rs780094 were determined in 177 severely obese patients who underwent bariatric surgery. NASH was evaluated by liver histopathology.Of 177 patients, 29 (16.4%), 57 (33.2%), and 91 (51.4%) were in the non-NAFLD, steatosis, and NASH groups, respectively. We found that the PPARGC1A and PNPLA3 variants, but not the GCKR variant, were associated with NASH. The PPARGC1A rs8192678 GA/AA genotype was associated with higher steatosis grade and presence of ballooning degeneration. The PNPLA3 rs738409 GG genotype was associated with higher severity in all histologic features except for fibrosis. In multivariate analysis, both the PPARGC1A rs8192678 GA/AA genotype (odds ratio [OR] 2.32; 95% confidence interval [CI] 1.08-4.98; P = 0.031) and the PNPLA3 rs738409 GG genotype (OR 4.05; 95% CI 1.24-13.23; P = 0.021), and also body mass index were independent risk factors for NASH. Further, there was an additive effect of the PPARGC1A rs8192678 GA/AA genotype and the PNPLA3 rs738409 GG genotype on the presence of NASH (OR 6.83; 95% CI 1.61-29.01; P = 0.009).The PPARGC1A rs8192678 GA/AA genotype and the PNPLA3 rs738409 GG genotype had an additive effect on NASH in severely obese Taiwanese patients.

The effects of IL-10 gene polymorphism on serum, and gingival crevicular fluid levels of IL-6 and IL-10 in chronic periodontitis.

PubMed

Toker, Hulya; Gorgun, Emine Pirim; Korkmaz, Ertan Mahir; Yüce, Hatice Balci; Poyraz, Omer

2018-01-01

Anti-inflammatory cytokines play a crucial role in periodontitis by inhibiting synthesis of pro-inflammatory cytokines. The purpose of this study was to evaluate the effect of interleukin-10 (-597) gene polymorphism and genotype distributions on chronic periodontitis (CP) development and IL-6 and IL-10 levels in gingival crevicular fluid (GCF) and serum before and after non-surgical periodontal treatment. The study population consisted of 55 severe generalized CP patients as CP group and 50 healthy individuals as control group. Plaque index, gingival index, probing depth and clinical attachment level were recorded and GCF and blood samples were taken at both the baseline and the sixth week after non-surgical periodontal treatment. PCR-RFLP procedure was used for gene analyses and cytokine levels were measured via ELISA. IL-10 genotype distribution was significantly different between CP and control groups (p=0.000, OR:7, 95%CI, 2.83-60.25). Clinical measurements significantly improved in the CP group after periodontal treatment (p<0.05). Periodontal treatment significantly decreased GCF IL-6 and IL-10 levels. No significant difference was found in clinical parameters between IL-10 AA and AC+CC genotypes at both the baseline and the sixth week (p>0.05). Sixth week GCF IL-10 levels were significantly lower in patients carrying IL-10 AC+CC genotype compared to the patients carrying IL-10 AA genotype (p<0.05). Serum IL-6 and IL-10 levels were lower in patients carrying the IL-10 AA genotype compared to patients with IL-10 AC+CC genotype, but the difference was not significant (p>0.05). IL-10 AA genotype carriers had lower IL-6 and IL-6/10 levels in serum; however, GCF IL-6/10 levels were similar in both genotypes. Within the limitations of our study, a possible association between IL-10(-597) gene polymorphism and CP might be considered.

Analysis of IL-6, IL-10 and NF-κB Gene Polymorphisms in Aggressive and Chronic Periodontitis.

PubMed

Toker, Hülya; Görgün, Emine Pirim; Korkmaz, Ertan Mahir

2017-06-01

Pro-inflammatory cytokines, interleukin-6 (IL-6), demonstrated to be suppressed by interleukin-10 (IL-10) are known to be regulated by the transcription factor nuclear factor-κB(NF-κB). The aim of this study was to ascertain the association between genetic polymorphism of these genes (IL-6(-174), IL-10(-597) and NF-κB1-94ins/del)) and chronic/aggressive periodontitis. Forty-five patients with chronic periodontitis (CP), 58 patients with aggressive periodontitis (AP) and 38 periodontally healthy subjects were included in this study. Genomic DNA was isolated from whole blood samples. The NF-κB, IL-6, and IL-10 polymorphisms were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Among subjects for the ins/ins genotypes of NF-κB1 gene, the AA genotypes of IL-10 presented a higher frequency in chronic periodontitis group than in healthy controls (p=0.023). A statistically significant difference in genotyping frequencies between AP group and healthy controls was observed for the IL-6 gene. The AA genotype of IL-10 was overrepresented in CP and AP groups compared to healthy controls (OR=9.93, 95% CI: 2.11-46.7, OR=5.7, 95% CI: 1.22-26.89, respectively). Within the limits of this study, it can be concluded that the IL-10 (-597) AA genotype is associated with susceptibility to chronic/aggressive periodontitis and IL-6 (-174) GG genotypes and G allele seems to be associated with aggressive periodontitis. Clinical relevance: The results of the current study indicate that IL-6 and IL-10 genotypes seem to be associated with aggressive periodontitis. Also, the AA genotypes of IL-10 presented a higher frequency in chronic periodontitis subjects with carrying NF-κB1 ins/ins genotypes. Copyright© by the National Institute of Public Health, Prague 2017

The relationship between anabolic androgenic steroids and muscle dysmorphia: a review.

PubMed

Rohman, Lebur

2009-01-01

This review explores the condition of muscle dysmorphia (MD) and its relationship with anabolic androgenic steroids (AAS). Particular emphasis is placed upon whether anabolic steroids are a predisposing, precipitating or perpetuating factor of MD. Furthermore, psychiatric complications of AAS abuse are examined. The current evidence from the literature suggests that AAS (ab)use is possibly a perpetuating factor in the evolution of MD. Psychiatric complications of AAS include mood and behavior changes, perceptual abnormalities, and withdrawal symptoms. In addition, there appears to be a credible dependence theory to AAS in fruition.

A polymorphism in the leptin receptor gene at position 223 is associated with growth hormone replacement therapy responsiveness in idiopathic short stature and growth hormone deficiency patients.

PubMed

Su, Pen-Hua; Yang, Shun-Fa; Yu, Ju-Shan; Chen, Suh-Jen; Chen, Jia-Yuh

2012-12-01

We hypothesized that responses to growth hormone (GH) therapy by idiopathic short stature (ISS) and growth hormone deficiency (GHD) patients were associated with single nucleotide polymorphisms (SNPs) in the leptin (LEP) and leptin receptor (LEPR) genes. We retrospectively enrolled ISS (n = 32) and GHD (n = 38) patients and forty healthy age-and gender-matched children. They were genotyped for the LEP promoter at nt.-2548, and LEPR K109R and LEPR Q223R polymorphisms. Clinical and laboratory variables were determined before and after 2 years of GH treatment. ISS patients with G/A or A/A genotypes of the LEPR Q223R SNP had a significantly higher height velocity (cm/y) than ISS patients with the G/G genotype at 2 years after GH treatment. For GHD patients, G/A or A/A genotype of the LEPR K109R SNP was associated with higher body weight, higher BMI, and higher weight velocity than patients with the G/G genotype before GH treatment, but not after GH treatment. G/A or A/A genotype of the LEPR Q223R SNP was associated with a significantly higher body weight, higher height velocity before treatment, but not after GH treatment. G/A or A/A genotype of the LEPR Q223R SNP was associated with a significantly higher weight velocity before treatment, but a significantly lower weight velocity was found at 2 years after GH treatment. These results suggest LEPR Q223R SNP (rs1137101) is associated with outcomes of GH replacement therapy in ISS and GHD patients. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Genetic Variations of the COL4A1 Gene and Intracerebral Hemorrhage Risk: A Case-Control Study in a Chinese Han Population.

PubMed

Lin, Sen; Xia, Chao; He, Sha; Yang, Jie; Li, Hao; Zheng, Jun; Liu, Ming; You, Chao

2018-04-01

To investigate the association between single nucleotide polymorphisms or haplotypes of the COL4A1 gene and the risk of intracerebral hemorrhage (ICH). We conducted a case-control study that included 181 patients from the Chinese Han population with hypertensive ICH and 197 hypertension patients without ICH. Genomic DNA was extracted by DNA extraction kit, and the 6 single nucleotide polymorphism genotypes of the COL4A1 gene were detected with a MassARRAY Analyzer. Unphased 3.1.4 and SPSS 19.0 were used to analyze the association between alleles, genotypes, and haplotypes of the COL4A1 gene and the risk of ICH. Compared with the control group, patients in the ICH group were significantly younger. There were no differences in gender, diabetes, hyperlipidemia, current smoking, and alcohol consumption between the 2 groups. Our association analysis showed that the rs3742207 A, rs11069830 A, and rs679505 A alleles were association factors of the risks of ICH; rs11069830 AA, rs544012 AC, and rs679505 AA genotypes were association factors of the risk of ICH; AA haplotype (rs3742207-rs11069830) was an association factor of the risk of ICH. After adjusting age and gender by multivariate logistic regression, the rs544012 AC and rs679505 AA genotypes were independently associated with the risk of ICH. Our study showed that the rs544012 AC and rs679505 AA genotypes were independently associated with the risk of ICH in the Chinese Han population and that the AA haplotype (rs3742207-rs11069830) in the COL4A1 gene may be related to the risk of ICH in the Chinese Han population; these conclusions need further confirmation in future studies with larger samples. Copyright © 2018. Published by Elsevier Inc.

APJ receptor A445C gene polymorphism in Turkish patients with coronary artery disease

PubMed Central

Akcılar, Raziye; Yümün, Gündüz; Bayat, Zeynep; Donbaloğlu, Okan; Erselcan, Kubilay; Ece, Ezgi; Kökdaşgil, Hülya; Genç, Osman

2015-01-01

Coronary artery disease (CAD) is a disease in which a waxy substance called plaque builds up inside the coronary arteries. Apelin is a novel endogenous peptide with inotropic and vasodilatory properties and is the ligand for the angiotensin receptor-like 1 (APJ) receptor. We aimed to determine genotype and allele frequencies of APJ receptor A445C gene polymorphism in Turkish patients with CAD and healthy controls by RFLP-PCR. This study was performed on 159 unrelated CAD patients and 62 healthy controls. We obtained AA, AC and CC genotype frequencies in CAD patients as 41.5%, 49.1% and 9.4%, respectively. In the control group, frequencies of genotypes were found as 35.5% for AA, 48.4% for AC and 16.1% for CC. We did not observe difference in APJ receptor A445C polymorphism between CAD patients and healthy controls (χ2 = 2.178; df = 2; P = 0.336). The A allele was encountered in 66% (210) of the CAD and 59.7% (74) of the controls. The C allele was seen in 34% (108) of the CAD and 40.3% (50) of the controls. Allele frequencies of interested genes were not significantly different between groups (χ2 = 1.57; df = 1; p = 0.225). The frequencies of APJ receptor A445C genotype were not significantly different between control and patients. None of the three APJ receptor A445C genotypes, AA, AC and CC displayed significant difference in CAD patients. We did not find any difference in the clinical parameters except for weight and diastolic blood pressure levels in the AA, AC and CC genotypes of patients. Individuals with CC genotypes had significantly higher weight, systolic and diastolic blood pressure levels and systolic blood pressure than other genotypes, P ≤ 0.05. In addition, HDL-C level was found decreased, but this reduction was not statistically significant. Contrarily, the low levels of weight, SBP, DBP and TC were statistically significant in the subjects with AA genotype in CAD. In conclusion, CC genotype carriers may have more risk than other genotypes in the development of hypertension in CAD, but not AAgenotype carriers. We suggest that this polymorphism may not be a marker of CAD, but it may cause useful in function of the apelin/APJ system and may be a genetic predisposing factor for diagnostic processes and can be helpfull in finding new treatment strategies. We think that it is required to further comprehensive studies in order to make clear this situation in CAD. PMID:26770497

Single amino acid insertions in extracellular loop 2 of Bombyx mori ABCC2 disrupt its receptor function for Bacillus thuringiensis Cry1Ab and Cry1Ac but not Cry1Aa toxins.

PubMed

Tanaka, Shiho; Miyamoto, Kazuhisa; Noda, Hiroaki; Endo, Haruka; Kikuta, Shingo; Sato, Ryoichi

2016-04-01

In a previous report, seven Cry1Ab-resistant strains were identified in the silkworm, Bombyx mori; these strains were shown to have a tyrosine insertion at position 234 in extracellular loop 2 of the ABC transporter C2 (BmABCC2). This insertion was confirmed to destroy the receptor function of BmABCC2 and confer the strains resistance against Cry1Ab and Cry1Ac. However, these strains were susceptible to Cry1Aa. In this report, we examined the mechanisms of the loss of receptor function of the transporter by expressing mutations in Sf9 cells. After replacement of one or two of the five amino acid residues in loop 2 of the susceptible BmABCC2 gene [BmABCC2_S] with alanine, cells still showed susceptibility, retaining the receptor function. Five mutants with single amino acid insertions at position 234 in BmABCC2 were also generated, resulting in loop 2 having six amino acids, which corresponds to replacing the tyrosine insertion in the resistant BmABCC2 gene [BmABCC2_R(+(234)Y)] with another amino acid. All five mutants exhibited loss of function against Cry1Ab and Cry1Ac. These results suggest that the amino acid sequence in loop 2 is less important than the loop size (five vs. six amino acids) or loop structure for Cry1Ab and Cry1Ac activity. Several domain-swapped mutant toxins were then generated among Cry1Aa, Cry1Ab, and Cry1Ac, which are composed of three domains. Swapped mutants containing domain II of Cry1Ab or Cry1Ac did not kill Sf9 cells expressing BmABCC2_R(+(234)Y), suggesting that domain II of the Cry toxin is related to the interaction with the receptor function of BmABCC2. This also suggests that different reactions against Bt-toxins in some B. mori strains, that is, Cry1Ab resistance or Cry1Aa susceptibility, are attributable to structural differences in domain II of Cry1A toxins. Copyright © 2016. Published by Elsevier Inc.

[Association of methionine synthase reductase gene polymorphism with unexplained recurrent spontaneous abortion].

PubMed

Guo, Qian-nan; Liao, Shi-xiu; Kang, Bing; Zhang, Ju-xin; Wang, Rui-li; Ding, Xue-bing; Zhang, Wei-hua

2012-10-01

To explore the relationship between the polymorphism of methionine synthase reductase (MTRR) A66G and the susceptibility to unexplained repeated spontaneous abortion (URSA). Total of 200 Henan Han couples with URSA (URSA group) and 76 Henan Han healthy couples without URSA (control group) were enrolled in this study. Their MTRR A66G genotypes were determined by PCR restriction fragment length polymorphism (PCR-RFLP). (1) The allele frequencies of MTRR A66G: the frequencies of allele A and allele G in URSA group were 76.5% (153/200) in husband and 72.8% (146/200) in wife, 23.5% (47/200) in husband and 27.2% (54/200) in wife, respectively. The frequencies of allele A and allele G in control group were 78.9% (60/76) in husband and 78.3% (59/76) in wife, 21.1% (16/76) in husband and 21.7% (16/76) in wife, respectively. The frequencies of allele A and allele G were not significantly different between female and male subjects within the same experimental group (P > 0.05), and also there were not significantly different between the same gender subjects at URAS and control groups (P > 0.05). (2) The genotype frequencies of MTRR A66G: the frequencies of genotype AA, AG and GG in URSA group were 57.0% (114/200) in husband and 52.0% (104/200) in wife, 39.0% (78/200) in husband and 41.5% (83/200) in wife, 4.0% (8/200) in husband and 6.5% (13/200) in wife, prepectively. The frequencies of genotype AA, AG and GG in control group were 59.2% (45/76) in husband and 59.2% (50/76) in wife, 39.5% (30/76) in husband and 38.2% (29/76) in wife; 1.3% (1/76) in husband and 2.6% (2/76) in wife, prepectively. The frequencies of genotype AA, AG and GG were not significantly different between female and male subjects within the same group (P > 0.05), and also there were not significantly different between the same gender subjects at URSA and control groups (P > 0.05).(3)Combined genotype of couples: the combined genotype frequencies of GG + GG, GG + AG, GG + AA, AG + AG, AG + AA and AA + AA in URSA group were 1.0% (2/200), 2.5% (5/200), 6.0% (12/200), 20.0% (40/200), 38.0% (76/200), and 32.5% (65/200), prepectively; the combined genotype frequencies in control group were 0, 1.3% (1/76), 2.6% (2/76), 17.1% (13/76), 42.1% (32/76), 36.8% (28/76), prepectively. The combined genotype analysis between the two groups were also not significantly different (P > 0.05). The polymorphism of MTRR A66G gene was not associated with the susceptibility to URSA (P > 0.05), and so it was not the inherited genetic risk factor of URSA.

APOL1 Genotype and Kidney Transplantation Outcomes From Deceased African American Donors.

PubMed

Freedman, Barry I; Pastan, Stephen O; Israni, Ajay K; Schladt, David; Julian, Bruce A; Gautreaux, Michael D; Hauptfeld, Vera; Bray, Robert A; Gebel, Howard M; Kirk, Allan D; Gaston, Robert S; Rogers, Jeffrey; Farney, Alan C; Orlando, Giuseppe; Stratta, Robert J; Mohan, Sumit; Ma, Lijun; Langefeld, Carl D; Bowden, Donald W; Hicks, Pamela J; Palmer, Nicholette D; Palanisamy, Amudha; Reeves-Daniel, Amber M; Brown, W Mark; Divers, Jasmin

2016-01-01

Two apolipoprotein L1 gene (APOL1) renal-risk variants in donors and African American (AA) recipient race are associated with worse allograft survival in deceased-donor kidney transplantation (DDKT) from AA donors. To detect other factors impacting allograft survival from deceased AA kidney donors, APOL1 renal-risk variants were genotyped in additional AA kidney donors. The APOL1 genotypes were linked to outcomes in 478 newly analyzed DDKTs in the Scientific Registry of Transplant Recipients. Multivariate analyses accounting for recipient age, sex, race, panel-reactive antibody level, HLA match, cold ischemia time, donor age, and expanded criteria donation were performed. These 478 transplantations and 675 DDKTs from a prior report were jointly analyzed. Fully adjusted analyses limited to the new 478 DDKTs replicated shorter renal allograft survival in recipients of APOL1 2-renal-risk-variant kidneys (hazard ratio [HR], 2.00; P = 0.03). Combined analysis of 1153 DDKTs from AA donors revealed donor APOL1 high-risk genotype (HR, 2.05; P = 3 × 10), older donor age (HR, 1.18; P = 0.05), and younger recipient age (HR, 0.70; P = 0.001) adversely impacted allograft survival. Although prolonged allograft survival was seen in many recipients of APOL1 2-renal-risk-variant kidneys, follow-up serum creatinine concentrations were higher than that in recipients of 0/1 APOL1 renal-risk-variant kidneys. A competing risk analysis revealed that APOL1 impacted renal allograft survival, but not recipient survival. Interactions between donor age and APOL1 genotype on renal allograft survival were nonsignificant. Shorter renal allograft survival is reproducibly observed after DDKT from APOL1 2-renal-risk-variant donors. Younger recipient age and older donor age have independent adverse effects on renal allograft survival.

Genetic polymorphisms involved in dopaminergic neurotransmission and risk for Parkinson's disease in a Japanese population

PubMed Central

2011-01-01

Background Parkinson's disease (PD) is characterized by alterations in dopaminergic neurotransmission. Genetic polymorphisms involved in dopaminergic neurotransmission may influence susceptibility to PD. Methods We investigated the relationship of catechol-O-methyltransferase (COMT), monoamine oxidase B (MAOB), dopamine receptor (DR) D2 and DRD4 polymorphisms and PD risk with special attention to the interaction with cigarette smoking among 238 patients with PD and 369 controls in a Japanese population. Results Subjects with the AA genotype of MAOB rs1799836 showed a significantly increased risk of PD (odds ratio (OR) = 1.70, 95% confidence interval (CI) = 1.12 - 2.58) compared with the AG and GG genotypes combined. The AA genotype of COMT rs4680 was marginally associated with an increased risk of PD (OR = 1.86, 95% CI = 0.98 - 3.50) compared with the GG genotype. The DRD2 rs1800497 and DRD4 rs1800955 polymorphisms showed no association with PD. A COMT -smoking interaction was suggested, with the combined GA and AA genotypes of rs4680 and non-smoking conferring significantly higher risk (OR = 3.97, 95% CI = 2.13 - 7.41) than the AA genotype and a history of smoking (P for interaction = 0.061). No interactions of smoking with other polymorphisms were observed. Conclusions The COMT rs4680 and MAOB rs1799836 polymorphisms may increase susceptibility to PD risk among Japanese. Future studies involving larger control and case populations and better pesticide exposure histories will undoubtedly lead to a more thorough understanding of the role of the polymorphisms involved in the dopamine pathway in PD. PMID:21781348

Lack of significant associations with early career performance suggest no link between the DMRT3 "Gait Keeper" mutation and precocity in Coldblooded trotters.

PubMed

Jäderkvist Fegraeus, Kim; Lawrence, Chameli; Petäjistö, Katrine; Johansson, Maria K; Wiklund, Maja; Olsson, Christina; Andersson, Leif; Andersson, Lisa S; Røed, Knut H; Ihler, Carl-Fredrik; Strand, Eric; Lindgren, Gabriella; Velie, Brandon D

2017-01-01

The Swedish-Norwegian Coldblooded trotter (CBT) is a local breed in Sweden and Norway mainly used for harness racing. Previous studies have shown that a mutation from cytosine (C) to adenine (A) in the doublesex and mab-3 related transcription factor 3 (DMRT3) gene has a major impact on harness racing performance of different breeds. An association of the DMRT3 mutation with early career performance has also been suggested. The aim of the current study was to investigate this proposed association in a randomly selected group of CBTs. 769 CBTs (485 raced, 284 unraced) were genotyped for the DMRT3 mutation. The association with racing performance was investigated for 13 performance traits and three different age intervals: 3 years, 3 to 6 years, and 7 to 10 years of age, using the statistical software R. Each performance trait was analyzed for association with DMRT3 using linear models. The results suggest no association of the DMRT3 mutation with precocity (i.e. performance at 3 years of age). Only two traits (race time and number of disqualifications) were significantly different between the genotypes, with AA horses having the fastest times and CC horses having the highest number of disqualifications at 3 years of age. The frequency of the AA genotype was significantly lower in the raced CBT sample compared with the unraced sample and less than 50% of the AA horses participated in a race. For the age intervals 3 to 6 and 7 to 10 years the AA horses also failed to demonstrate significantly better performance than the other genotypes. Although suggested as the most favorable genotype for racing performance in Standardbreds and Finnhorses across all ages, the AA genotype does not appear to be associated with superior performance, early or late, in the racing career of CBTs.

Lack of significant associations with early career performance suggest no link between the DMRT3 “Gait Keeper” mutation and precocity in Coldblooded trotters

PubMed Central

Lawrence, Chameli; Petäjistö, Katrine; Johansson, Maria K.; Wiklund, Maja; Olsson, Christina; Andersson, Leif; Andersson, Lisa S; Røed, Knut H.; Ihler, Carl-Fredrik; Strand, Eric

2017-01-01

The Swedish-Norwegian Coldblooded trotter (CBT) is a local breed in Sweden and Norway mainly used for harness racing. Previous studies have shown that a mutation from cytosine (C) to adenine (A) in the doublesex and mab-3 related transcription factor 3 (DMRT3) gene has a major impact on harness racing performance of different breeds. An association of the DMRT3 mutation with early career performance has also been suggested. The aim of the current study was to investigate this proposed association in a randomly selected group of CBTs. 769 CBTs (485 raced, 284 unraced) were genotyped for the DMRT3 mutation. The association with racing performance was investigated for 13 performance traits and three different age intervals: 3 years, 3 to 6 years, and 7 to 10 years of age, using the statistical software R. Each performance trait was analyzed for association with DMRT3 using linear models. The results suggest no association of the DMRT3 mutation with precocity (i.e. performance at 3 years of age). Only two traits (race time and number of disqualifications) were significantly different between the genotypes, with AA horses having the fastest times and CC horses having the highest number of disqualifications at 3 years of age. The frequency of the AA genotype was significantly lower in the raced CBT sample compared with the unraced sample and less than 50% of the AA horses participated in a race. For the age intervals 3 to 6 and 7 to 10 years the AA horses also failed to demonstrate significantly better performance than the other genotypes. Although suggested as the most favorable genotype for racing performance in Standardbreds and Finnhorses across all ages, the AA genotype does not appear to be associated with superior performance, early or late, in the racing career of CBTs. PMID:28489879

Vitamin D receptor gene polymorphisms and the risk of rickets among Asians: a meta-analysis.

PubMed

Mao, Song; Huang, Songming

2014-03-01

To evaluate the association between vitamin D receptor (VDR) gene polymorphisms and the risk of rickets among Asians. Eligible studies were included in our meta-analysis by searching PubMed, Embase, Cochrane and China National Knowledge Infrastructure databases according to a predefined criteria. A random effects model was used to calculate the combined ORs and its corresponding 95% CI. 16 studies were recruited for the analysis of the association between VDR BsmI (rs1544410), TaqI (rs731236), FokI (rs2228570) and ApaI (rs7975232) gene polymorphisms and the risk of rickets among Asians, most of whom were from China. B allele/BB genotype was associated with the susceptibility of rickets (p=0.017 and 0.044, respectively), and bb genotype was associated with lower risk of rickets (p=0.033). F allele/FF genotype was associated with the susceptibility of rickets (p<10(-4)), and ff genotype was associated with lower risk of rickets (p<10(-4)). AA genotype was associated with the onset of rickets (p=0.044). No significant association was observed between TaqI polymorphism the risk of rickets. A allele/aa genotype was not associated with the risk of rickets. No evidence of publication bias was observed. B allele/BB genotype at the BsmI site, F allele/FF genotype at the FokI site and AA genotype at the ApaI site may be risk factors for the onset of rickets among Asians; bb genotype at the BsmI site and ff genotype at the FokI site may be protective factors against the risk of rickets among Asians.

Role of toll-like receptor 10 gene polymorphism and gastric mucosal pattern in patients with chronic gastritis.

PubMed

Tongtawee, Taweesak; Bartpho, Theeraya; Wattanawongdon, Wareeporn; Dechsukhum, Chavaboon; Leeanansaksiri, Wilairat; Matrakool, Likit; Panpimanmas, Sukij

2017-07-01

Helicobacter pylori stimulates the host's toll-like receptors (TLRs). Single-nucleotide polymorphism (SNP) of TLRs is related to the manipulation of regulatory cytokines and also implicated in the varied outcomes of the inflammatory response, including the development of precancerous lesions of gastric mucosa and disease progression. We hypothesized that TLR10 rs10004195 polymorphism is associated with gastric mucosal patterns. TLR10 rs10004195 polymorphisms were identified in a total of 400 gastritis patients using the TagMan SNP genotyping assay. Gastric mucosal patterns were classified by Conventional Narrow Band Imaging gastroscopy (C-NBI gastroscopy). Logistic regression was used to analyze the association. The gastritis patients was Type 1, 37.5% of Thai patients. The T/T homozygous genotype was exhibited by the highest percentage (46.5%) of patients, and the A/A homozygous and A/T heterozygous genotypes were exhibited by 20.25% and 33.25%, respectively, of patients. TLR10 rs10004195 was significantly associated with gastric mucosal patterns. After adjusting for confounding factors, patients with the A/A homozygous genotype showed a significantly increased risk of severe inflammation (OR=1.35, 95% CI=0.97-2.13, p=0.028). Patients with the A/T heterozygous and T/T homozygous genotypes showed a significantly increased risk of mild inflammation (OR=1.24, 95% CI=0.78-2.07, p=0.042 and OR=1.78, 95% CI=0.51-3.35, p=0.001, respectively). Our results indicate that the presence of TLR10 rs10004195, A/T heterozygous, and T/T homozygous genotypes is associated with type 1, 2, and 3 whereas that of the A/A homozygous genotype is associated with type 4 and 5 of gastric mucosal patterns. This suggests that the A/A homozygous genotype contributes to severe inflammation in H. pylori-associated gastritis in Thai patients.

Molecular characterization and expression profile of partial TLR4 gene in association to mastitis in crossbred cattle.

PubMed

Panigrahi, Manjit; Sharma, Arjava; Bhushan, Bharat

2014-01-01

Crossbred cattle are more prone to mastitis in comparison to indigenous cattle. Toll-like receptor 4 (TLR4) recognizes pathogen ligands, for example, lipopolysaccharide (LPS) endotoxin from Escherichia coli and mediates signaling to initiate innate and adaptive immune responses. Mutations in TLR4 can compromise the host immune response to certain pathogens, so it may be a potential candidate for marker assisted selection to enhance mastitis resistance in dairy cattle. Hence, in this study role of bovine TLR4 gene in mastitis resistance was investigated by association as well as expression profiling analysis in crossbred cattle. The animals were divided into mastitis affected and unaffected groups on the basis of history of animals and California Mastitis Test (CMT). PCR-SSCP and Sequence analysis revealed three genotypes of coreceptor binding region 1 (CRBR1) fragment of TLR4 gene namely AA, AB, and BB in both groups of cattle. The logistic regression model did not show any significant effect of these genotypes on the occurrence of clinical mastitis. Moreover, in vitro challenge of peripheral blood mononuclear cells (PBMCs) with LPS failed to show any association of the genotypes with TLR4 gene expression. In a nutshell, in the present study enough evidence was not found for association of the SNP variants of CRBR1 fragment of TLR4 gene with mastitis susceptibility in crossbred cattle.

Can Non-HLA Single Nucleotide Polymorphisms Help Stratify Risk in TrialNet Relatives at Risk for Type 1 Diabetes?

PubMed

Steck, Andrea K; Xu, Ping; Geyer, Susan; Redondo, Maria J; Antinozzi, Peter; Wentworth, John M; Sosenko, Jay; Onengut-Gumuscu, Suna; Chen, Wei-Min; Rich, Stephen S; Pugliese, Alberto

2017-08-01

Genome-wide association studies identified >50 type 1 diabetes (T1D) associated non-human leukocyte antigens (non-HLA) loci. The purpose of this study was to assess the contribution of non-HLA single nucleotide polymorphisms (SNPs) to risk of disease progression. The TrialNet Pathway to Prevention Study follows relatives of T1D patients for development of autoantibodies (Abs) and T1D. Using the Immunochip, we analyzed 53 diabetes-associated, non-HLA SNPs in 1016 Ab-positive, at-risk non-Hispanic white relatives. Effect of SNPs on the development of multiple Abs and T1D. Cox proportional analyses included all substantial non-HLA SNPs, HLA genotypes, relationship to proband, sex, age at initial screening, initial Ab type, and number. Factors involved in progression from single to multiple Abs included age at screening, relationship to proband, HLA genotypes, and rs3087243 (cytotoxic T lymphocyte antigen-4). Significant factors for diabetes progression included age at screening, Ab number, HLA genotypes, rs6476839 [GLIS family zinc finger 3 (GLIS3)], and rs3184504 [SH2B adaptor protein 3 (SH2B3)]. When glucose area under the curve (AUC) was included, factors involved in disease progression included glucose AUC, age at screening, Ab number, relationship to proband, HLA genotypes, rs6476839 (GLIS3), and rs7221109 (CCR7). In stratified analyses by age, glucose AUC, age at screening, sibling, HLA genotypes, rs6476839 (GLIS3), and rs4900384 (C14orf64) were significantly associated with progression to diabetes in participants <12 years old, whereas glucose AUC, sibling, rs3184504 (SH2B3), and rs4900384 (C14orf64) were significant in those ≥12. In conclusion, we identified five non-HLA SNPs associated with increased risk of progression from Ab positivity to disease that may improve risk stratification for prevention trials. Copyright © 2017 by the Endocrine Society

Association of aplastic anemia and FoxP3 gene polymorphisms in Koreans.

PubMed

In, Ji Won; Lee, Nuri; Roh, Eun Youn; Shin, Sue; Park, Kyoung Un; Song, Eun Young

2017-04-01

Aplastic anemia (AA) is characterized by pancytopenia and bone marrow failure, and most acquired AA is an immune-mediated disorder. Regulatory T cells (T regs ) suppressing autoreactive T cells were decreased in AA patients. FoxP3 is a major regulator for the development and function of T regs . Polymorphism in FoxP3 was shown to be associated with various autoimmune diseases, however, has not yet been studied in AA. In this study, we examined the association between FoxP3 polymorphisms and AA in Korean patients. The study population consisted of 94 patients diagnosed by bone marrow examination in Seoul National University Hospital (SNUH) during 1997-2012 and 195 healthy controls. FoxP3 polymorphisms (rs5902434 del/ATT, rs3761548 C/A, rs3761549 C/T, rs2232365 A/G) were analyzed by PCR-sequencing method. We analyzed differences of genotype and allele frequencies between patients and controls. We also compared differences of genotype and allele frequencies between responder and non-responder in patients treated with immunosuppressive therapy (IST). For the statistical analysis, the chi-square test and Fisher's exact test were used and P < 0.05 was regarded as statistically significant. There was no significant difference in the genotype frequencies of FoxP3 polymorphisms between patients and controls. With regards to the allele frequencies, rs3761548 C allele was significantly higher in AA patients than in controls (87.4% vs. 79.7%, P = 0.047). In patients treated with IST, rs3761549 C allele was significantly higher in non-responder patients than in responders (89.6% vs. 66.7%, P = 0.036) and female rs3761549 C/C genotype carriers were associated with greater risk for non-response to IST (84.2% vs. 16.7%, P = 0.006). Polymorphisms in rs3761548 and rs3761549 of FoxP3 in our population were associated with disease susceptibility and response for IST, respectively. This study suggests an association between FoxP3 polymorphisms and AA in Korean patients and will be useful in further understanding the genetic basis of disease susceptibility and response to IST in AA patients.

Oxytocin and Social Sensitivity: Gene Polymorphisms in Relation to Depressive Symptoms and Suicidal Ideation

PubMed Central

McQuaid, Robyn J.; McInnis, Opal A.; Matheson, Kimberly; Anisman, Hymie

2016-01-01

Although the neuropeptide oxytocin has been associated with enhanced prosocial behaviors, it has also been linked to aggression and mental health disorders. Thus, it was suggested that oxytocin might act by increasing the salience of social stimuli, irrespective of whether these are positive or negative, thus increasing vulnerability to negative mental health outcomes. The current study (N = 243), conducted among white university students, examined the relation of trauma, depressive symptoms including suicidal ideation in relation to a single nucleotide polymorphism (SNP) within the oxytocin receptor gene (OXTR), rs53576, and a SNP on the CD38 gene that controls oxytocin release, rs3796863. Individuals with the polymorphism on both alleles (AA genotype) of the CD38 SNP had previously been linked to elevated plasma oxytocin levels. Consistent with the social sensitivity perspective, however, in the current study, individuals carrying the AA genotype displayed elevated feelings of alienation from parents and peers as well as increased levels of suicidal ideation. Moreover, they tended to report elevated depressive symptoms compared to CC homozygotes. It was also observed that the CD38 genotype moderated the relation between trauma and suicidal ideation scores, such that high levels of trauma were associated with elevated suicidal ideation among all CD38 genotypes, but this relationship was stronger among individuals with the AA genotype. In contrast, there was no relationship between the OXTR SNP, rs53576, depression or suicidal ideation. These findings support a social sensitivity hypothesis of oxytocin, wherein the AA genotype of the CD38 SNP, which has been considered the “protective allele” was associated with increased sensitivity and susceptibility to disturbed social relations and suicidal ideation. PMID:27486392

Polymorphisms of genes encoding tumor necrosis factor-alpha, interleukin-10, cluster of differentiation-14 and interleukin-1ra in critically ill patients.

PubMed

Surbatovic, Maja; Grujic, Krasimirka; Cikota, Bojana; Jevtic, Miodrag; Filipovic, Nikola; Romic, Predrag; Strelic, Natasa; Magic, Zvonko

2010-09-01

The aim of the study was to determine whether distributions of tumor necrosis factor (TNF)-α(308), interleukin (IL)-10(1082), CD14(159), and IL-1ra gene intron 2 genotypes in critically ill patients are associated with outcome, underlying cause of sepsis, and type of microorganism. Blood samples from 106 critically ill white patients were genotyped by method based on polymerase chain reaction for TNF-α(308), IL-10(1082), CD14(159), and IL-1ra gene intron 2. All patients with TNF-α(308)AA genotype survived; relative risk (RR) of death in patients with AG was 3.250 and with GG, 1.923 (P < .01). In patients with Gram-positive sepsis, IL-10(1082)AA and then AG genotypes were the most frequent ones (odds ratio [OR], 18.67 and 7.20, respectively; P < .01). When comparing IL-10(1082)AA with AG, RR of pancreatitis was 1.80 and OR was 3.40. When AA and GG were compared, RR was 7.33 and OR was 20.00. In patients with GG, RR of peritonitis was 4.07 and OR was 5.88 (P < .01). In patients with Gram-positive sepsis, CD14(159)CT was the most frequent one with OR of 5.25. Distribution of 6 IL-1ra gene intron 2 genotypes showed no significant association. Distribution of TNF-α(308) genotypes is associated with outcome, IL-10(1082) with type of microorganism and underlying cause of sepsis, and CD14(159) with type of microorganism. Copyright © 2010. Published by Elsevier Inc.

Analytical Validation of a Personalized Medicine APOL1 Genotyping Assay for Nondiabetic Chronic Kidney Disease Risk Assessment.

PubMed

Zhang, Jinglan; Fedick, Anastasia; Wasserman, Stephanie; Zhao, Geping; Edelmann, Lisa; Bottinger, Erwin P; Kornreich, Ruth; Scott, Stuart A

2016-03-01

The incidence of chronic kidney disease (CKD) varies by ancestry, with African Americans (AA) having a threefold to fourfold higher rate than whites. Notably, two APOL1 alleles, termed G1 [c.(1072A>G; 1200T>G)] and G2 (c.1212_1217del6), are strongly associated with higher rates of nondiabetic CKD and an increased risk for hypertensive end-stage renal disease. This has prompted the opportunity to implement APOL1 testing to identify at-risk patients and modify other risk factors to reduce the progression of CKD to end-stage renal disease. We developed an APOL1 genotyping assay using multiplex allele-specific primer extension, and validated using 58 positive and negative controls. Genotyping results were completely concordant with Sanger sequencing, and both triplicate interrun and intrarun genotyping results were completely concordant. Multiethnic APOL1 allele frequencies were also determined by genotyping 7059 AA, Hispanic, and Asian individuals from the New York City metropolitan area. The AA, Hispanic, and Asian APOL1 G1 and G2 allele frequencies were 0.22 and 0.13, 0.037 and 0.025, and 0.013 and 0.004, respectively. Notably, approximately 14% of the AA population carried two risk alleles and are at increased risk for CKD, compared with <1% of the Hispanic and Asian populations. This novel APOL1 genotyping assay is robust and highly accurate, and represents one of the first personalized medicine clinical genetic tests for disease risk prediction. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Leptin expression and leptin receptor gene polymorphisms in growth hormone deficiency patients.

PubMed

Su, Pen-Hua; Chen, Jia-Yuh; Yu, Ju-Shan; Chen, Suh-Jen; Yang, Shun-Fa

2011-04-01

Growth hormone deficiency (GHD) patients have lower weight, height, bone age, insulin-like growth factor 1 (IGF-1) levels, GH levels, fat metabolism and skeletal growth. The association of leptin with GHD characteristics and the effect of gene variants of leptin on GHD are unknown. Our aim was to examine the association of circulating leptin levels and common genetic variants in leptin (LEP) and leptin receptor (LEPR) genes with anthropometric measures, circulating hormone concentrations and GHD. A case control study of 125 GHD cases and 159 control subjects were characterized for bone age, body mass index (BMI), height, weight, leptin, IGF-1, GH and their genotype at the leptin promoter G-2548A, and LEPR variants, K109R and Q223R, at Chung Shan Medical University Hospital. Leptin levels were significantly associated with lower bone age, weight and BMI in GHD patients. Leptin levels were also significantly associated with reduced IGF-1 levels in girls but not boys in both groups. The frequency of LEPR223 [A/G or A/A] genotype was significantly higher than the LEPR223 G/G genotype in the GHD group. The LEPR223 [A/G or A/A] genotype was significantly associated with increased weight and BMI in the control group, but not in the GHD group. In conclusion, the GHD group carried a significantly higher frequency of the LEPR [G/A or A/A] genotype and of the A allele (LEPR223R). The LEPR223R polymorphism affected weight and BMI in control, but not in GHD patients, suggesting that the effect of LEPR223 [A/G or A/A] genotype was counteracted by other factor(s) in GHD patients.

Combined genotype and haplotype distributions of MTHFR C677T and A1298C polymorphisms

PubMed Central

Fan, Shujun; Yang, Boyi; Zhi, Xueyuan; Wang, Yanxun; Zheng, Quanmei; Sun, Guifan

2016-01-01

Abstract Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms are, independently and/or in combination, associated with many disorders. However, data on the combined genotype and haplotype distributions of the 2 polymorphisms in Chinese population were limited. We recruited 13,473 adult women from 9 Chinese provinces, collected buccal cell samples, and determined genotypes, to estimate the combined genotype and haplotype distributions of the MTHFR C677T and A1298C polymorphisms. In the total sample, the 6 common combined genotypes were CT/AA (29.5%), TT/AA (21.9%), CC/AA (15.4%), CC/AC (14.9%), CT/AC (13.7%), and CC/CC (3.4%); the 3 frequent haplotypes were 677T-1298A (43.6%), 677C-1298A (37.9%), and 677C-1298C (17.6%). Importantly, we observed that there were 51 (0.4%) individuals with the CT/CC genotype, 92 (0.7%) with the TT/AC genotype, 17 (0.1%) with the TT/CC genotype, and that the frequency of the 677T-1298C haplotype was 0.9%. In addition, the prevalence of some combined genotypes and haplotypes varied among populations residing in different areas and even showed apparent geographical gradients. Further linkage disequilibrium analysis showed that the D’ and r2 values were 0.883 and 0.143, respectively. In summary, the findings of our study provide further strong evidence that the MTHFR C677T and A1298C polymorphisms are usually in trans and occasionally in cis configurations. The frequencies of mutant genotype combinations were relatively higher in Chinese population than other populations, and showed geographical variations. These baseline data would be useful for future related studies and for developing health management programs. PMID:27902594

Radial velocities of southern visual multiple stars

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tokovinin, Andrei; Pribulla, Theodor; Fischer, Debra, E-mail: atokovinin@ctio.noao.edu, E-mail: pribulla@ta3.sk, E-mail: debra.fischer@gmail.com

2015-01-01

High-resolution spectra of visual multiple stars were taken in 2008–2009 to detect or confirm spectroscopic subsystems and to determine their orbits. Radial velocities of 93 late-type stars belonging to visual multiple systems were measured by numerical cross-correlation. We provide the individual velocities, the width, and the amplitude of the Gaussians that approximate the correlations. The new information on the multiple systems resulting from these data is discussed. We discovered double-lined binaries in HD 41742B, HD 56593C, and HD 122613AB, confirmed several other known subsystems, and constrained the existence of subsystems in some visual binaries where both components turned out tomore » have similar velocities. The orbits of double-lined subsystems with periods of 148 and 13 days are computed for HD 104471 Aa,Ab and HD 210349 Aa,Ab, respectively. We estimate individual magnitudes and masses of the components in these triple systems and update the outer orbit of HD 104471 AB.« less

The polymorphisms of bovine VEGF gene and their associations with growth traits in Chinese cattle.

PubMed

Pang, Yonghong; Wang, Juqiang; Zhang, Chunlei; Lei, Chuzhao; Lan, Xianyong; Yue, Wangping; Gu, Chuanwen; Chen, Danxia; Chen, Hong

2011-02-01

PCR-SSCP and DNA sequencing methods were employed to screen the genetic variation of VEGF gene in 671 individuals belonging to three Chinese indigenous cattle breeds including Nanyang, Jiaxian Red and Qinchuan. Three haplotypes (A, B and C), four observed genotypes (AA, AB, BB and AC) and three new SNPs (6765T>C ss130456744, 6860A>G ss130456745, 6893T>C ss130456746) were detected. The analysis suggested that one SNP (ss130456744) in the bovine VEGF gene had significant effects on birth weight, body weight and heart girth at 6 months old in the Nanyang breed (P < 0.05). The results showed that the SNP (ss130456744) in intron 2 of the VEGF gene is associated with early development and growth of Chinese cattle. These findings raise hope that this polymorphism can be a molecular breeding marker in breeding strategies through marker assisted selection (MAS) in Chinese domestic cattle.

Allelic Prevalence of ABO Blood Group Genes in Iranian Azari Population

PubMed Central

Nojavan, Mohammad; Shamsasenjan, Karrim; Movassaghpour, Ali Akbar; Akbarzadehlaleh, Parvin; Torabi, Seyd Esmail; Ghojazadeh, Morteza

2012-01-01

Introduction ABO blood group system is the most important blood group in transfusion and has been widely used in population studies. Several molecular techniques for ABO allele’s detection are widely used for distinguishing various alleles of glycosyl transferase locus on chromosome 9. Methods 744 randomly selected samples from Azari donors of East Azerbaijan province (Iran) were examined using well-adjusted multiplex allele- specific PCR ABO genotyping technique. Results The results were consistent for all individuals. The ABO blood group genotype of 744 healthy Azari blood donors was: 25.8% AA/AO (2), 7.6% AO (1), 1.6% BB, 11.3% B0 (1), 10% AB, 9.3% 0(1)0(1) and 15.3%0(1)0(2). The highest genotype frequency belonged to O01/O02 genotype (15.3%) and the lowest frequency belonged to A101/A102 genotype (0.4%). Conclusions: The frequencies of ABO alleles didn’t show significant differences between East Azerbaijan province population and that of other areas of the country. Meanwhile, statistical analysis of frequencies of A and B alleles between East Azerbaijan province population and neighbor countries showed significant differences whereas the frequency of allele O between them did not show significant difference (P>0.05). Conclusions The frequencies of ABO alleles didn’t show significant differences between East Azerbaijan province population and that of other areas of the country. Meanwhile, statistical analysis of frequencies of A and B alleles between East Azerbaijan province population and neighbor countries showed significant differences whereas the frequency of allele O between them did not show significant difference (P>0.05). PMID:23678461

AB014. Beta-ketothiolase deficiency: phenotype, genotype and outcome of 48 Vietnamese patients

PubMed Central

Nguyen, Khanh Ngoc; Nguyen, Hoan Thi; Can, Ngoc Thi Bich; Do, Mai Thi Thanh; Bui, Thao Phuong; Fukao, Toshiyuki; Vu, Dung Chi

2017-01-01

Background Beta-ketothiolase deficiency (BKT) is an inherited metabolic disease of isoleucine and ketone body caused by mutations in the T2 gene. It is a rare disease with over 100 patients reported worldwide. We aimed to describe phenotypes and genotypes and to evaluate outcomes of Vietnamese patients with BKT. Methods Patients who were diagnosed with BKT, and followed up at National Children Hospital from January 2015 to June 2017 were enrolled. Results Forty-eight patients from 40 different and unrelated families were diagnosed through high risk screening in Vietnam. Forty-six patients (96%) presented with acute episodes of intermittent ketotic acidosis (pH <7.1, increased anion gap), and were asymptomatic between episodes. Ages of onset were between 6 and 18 months. Characteristics of metabolic chemistry revealed elevated urinary 2-methylacetoacetate, 2-methyl-3-hydroxybutyrate, tiglylglycine, and plasma C5:1 and C5:OH carnitines. We identified 8 different mutations with 9 kinds of genotypes. The common mutations of T2 gene were p.R208X and IVS10-1g>c (85%). Five novel mutations were identified (IVS10-1g>c, c.1032_1033insA, p.S284N, exon 6 -11del, and c.163_167delinsAA). Eight out of nine genotypes were null mutations. There was no correlation between genotypes and phenotypes. The outcome was good in most patients with 83% had complete recovery, 7% mental consequences, and 12% death. All patients had normal growth rate according to growth chart by World Health Organization (WHO) 2007. Conclusions BKT is a common inborn error of metabolism in Vietnam with good outcome in most patients. A newborn screening program for BKT may have a high detection rate in Vietnam.

Angiotensin II type 1 receptor gene polymorphism could influence renoprotective response to losartan treatment in type 1 diabetic patients with high urinary albumin excretion rate.

PubMed

Dragović, Tamara; Ajdinović, Boris; Hrvacević, Rajko; Ilić, Vesna; Magić, Zvonko; Andelković, Zoran; Kocev, Nikola

2010-04-01

Diabetic nephropathy (DN) is a clinical syndrome characterized by persistent albuminuria, increasing arterial blood pressure and progressive decline in glomerular filtration rate (GFR). When persistent albuminuria is established, antihypertensive treatment becomes most important factor in slowing the progression of diabetic glomerulopathy. The aim of this study was to examine if renoprotective response to a short-term losartan therapy depends on 1166 A/C gene polymorphism for its target receptor. The study included 35 patients with diabetes mellitus type 1 and persistently high urinary albumin excretion rate (UAE: > 30 mg/24 h), genotyped for the 1166 A/C gene polymorphism for the angiotensin II type 1 receptor (AT1R). The participants were segregated into 3 genotype groups according to combinations of A or C allele: AA (16%), AC (15%) and CC (11%). The patients received losartan 50 mg daily for 4 weeks, following 100 mg daily for another 8 weeks. At baseline and after 12 weeks of the treatment period UAE, blood pressure, GFR and filtration fraction (FF) were determined. After 12 weeks of the treatment with losartan, albuminuria was reduced from baseline by 9% [95% confidence interval (CI): 1-17, p = 0.039] in the AA genotype, and by 11% (95% CI: 6-17, p = 0.0001) in the AC genotype. Losartan treatment reduced albuminuria in the CC group by 5% (95% CI: -13-22, p = 0.47). Glomerular filtration rate remained unchanged in all genotype groups. Filtration fraction was significantly reduced from baseline by 0.018 +/- 0.024 (p = 0.012) only in the AC genotype. In the AA genotype, FF was reduced from baseline by 0.017 +/- 0.03 (p = 0.052), and in the CC genotype by 0.01 +/- 0.008 (p = 0.092). In the AA group, systolic blood pressure declined from 136 +/- 24 mmHg at baseline, to an average of 121 +/- 18 mmHg at the end of the study (p = 0.001). The AC group achived reduction from 131 +/- 10 mmHg at baseline to 115 +/- 7 mmHg (p = 0.001) during the investigation period. In the AA genotype group losartan reduced diastolic blood pressure from 86 +/- 13 mmHg at baseline to 78 +/- 8 mmHg (p = 0.004), and in the AC genotype from 88 +/- 5 mmHg at baseline to 11.7 +/- 5.6 mmHg during the investigation period (p = 0.001). In the CC genotype diastolic blood pressure reduction remained nonsignificant (p = 0.066). The results of our small sample size study provide the evidence that 1166 A/C AT1R polymorphism could be associated with the renoprotective response to losartan therapy.

Association of -1082 interleukin-10 gene polymorphism in Peruvian adults with chronic periodontitis

PubMed Central

Chambrone, Leandro; Ascarza, Amilcar; Guerrero, Maria E.; Pannuti, Claudio; de la Rosa, Manuel; Salinas-Prieto, Elmer

2014-01-01

Objectives: The aim of this study was to assess association of the -1082 IL-10 gene polymorphism with chronic periodontitis CP in a Peruvian population. Study Design: Samples of venous blood and DNA were obtained from 106 Peruvian subjects: a) 53 periodontally healthy; and b) 53 with CP. The association of the -1082 IL-10 promoter sequences was assessed by Polymerase chain reaction-restriction fragment length polymorfism (PCR-RFLP). Student’s t test were used to assess the clinical parameters, as well as the χ2 test and the odds ratio (OR), with 95% confidence intervals (CI) used performed for estimates regarding genotype and allele frequencies. Results: There were statistically significant differences between groups regarding the mean bleeding on probing, mean attachment level and mean probing depth (p < 0.00001) indicating that the matching based on the evaluated groups was adequate. The χ2 test found a statistically significant imbalance of genotypes between groups (p = 0.0172). The prevalence of CP was significantly higher in subjects harboring at least one A allele at position -1082 (AA and GA genotypes) in comparison to patients with the GG genotype (OR = 2.96; CI: 0.52; 5.41; p = 0.0099). Equally, subjects with the AA genotype were significantly associated to a diagnosis of CP (OR = 2.71; CI: 0.38; 5.04; p = 0.0231). On the other hand, subjects presenting a healthy periodontal status presented at least one G allele in comparison with the AA genotype (OR = 0.37; CI: 0.05, 0.69; p = 0.0231). For subjects with the GG genotype, the same positive association was observed (OR = 0.34; CI: 0.06, 0.62; p = 0.0099). There were no significant differences between groups amongst subjects with the GA genotype (OR = 1.19; CI: 0.22, 2.16; p = 0.6774). Conclusions: Within the limits of this study, IL-10 gene polymorphism at position -1082 does not appear to be associated to CP. Conversely, subjects with AA genotype seem to be at an increased risk of developing CP. Key words:According to MeSH documentation, chronic periodontitis, cytokines, genetic polymorphism, interleukin-10, periodontal disease. PMID:25129246

Association of -1082 interleukin-10 gene polymorphism in Peruvian adults with chronic periodontitis.

PubMed

Chambrone, Leandro; Ascarza, Amilcar; Guerrero, Maria-Eugenia; Pannuti, Claudio; de la Rosa, Manuel; Salinas-Prieto, Elmer; Mendoza, Gerardo

2014-11-01

The aim of this study was to assess association of the -1082 IL-10 gene polymorphism with chronic periodontitis CP in a Peruvian population. Samples of venous blood and DNA were obtained from 106 Peruvian subjects: a) 53 periodontally healthy; and b) 53 with CP. The association of the -1082 IL-10 promoter sequences was assessed by Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Student's t test were used to assess the clinical parameters, as well as the χ2 test and the odds ratio (OR), with 95% confidence intervals (CI) used performed for estimates regarding genotype and allele frequencies. There were statistically significant differences between groups regarding the mean bleeding on probing, mean attachment level and mean probing depth (p < 0.00001) indicating that the matching based on the evaluated groups was adequate. The χ2 test found a statistically significant imbalance of genotypes between groups (p = 0.0172). The prevalence of CP was significantly higher in subjects harboring at least one A allele at position -1082 (AA and GA genotypes) in comparison to patients with the GG genotype (OR = 2.96; CI: 0.52; 5.41; p = 0.0099). Equally, subjects with the AA genotype were significantly associated to a diagnosis of CP (OR = 2.71; CI: 0.38; 5.04; p = 0.0231). On the other hand, subjects presenting a healthy periodontal status presented at least one G allele in comparison with the AA genotype (OR = 0.37; CI: 0.05, 0.69; p = 0.0231). For subjects with the GG genotype, the same positive association was observed (OR = 0.34; CI: 0.06, 0.62; p = 0.0099). There were no significant differences between groups amongst subjects with the GA genotype (OR = 1.19; CI: 0.22, 2.16; p = 0.6774). Within the limits of this study, IL-10 gene polymorphism at position -1082 does not appear to be associated to CP. Conversely, subjects with AA genotype seem to be at an increased risk of developing CP.

Possible association of FAS and FASLG polymorphisms with the risk of idiopathic azoospermia in southeast Turkey.

PubMed

Balkan, Mahmut; Atar, Murat; Erdal, Mehmet Emin; Rustemoğlu, Aydin; Yildiz, Ismail; Gunesacar, Ramazan; Hatipoğlu, Namık Kemal; Bodakçi, Mehmet Nuri; Ay, Ozlem Izci; Çevik, Kenan

2014-06-01

To investigate the association of the genetic variants of FAS/FASLG cell death pathway genes in male infertility, we genotyped the FAS -670A/G, -1377G/A, and FASLG -124A/G single-nucleotide polymorphisms (SNPs) by real-time polymerase chain reaction in 108 infertile men with idiopathic azoospermia and in 125 proven fertile controls. The distribution of genotypes and alleles for SNPs at FAS -1377G/A and FASLG -124A/G loci were determined not to be statistically different between the case and control groups. However, the genotype frequencies of SNPs, FAS -670AA and FAS -670AG, were found to be significantly different between the case and control groups. Whereas the FAS -670AA genotype might be regarded as a higher predisposition for idiopathic azoospermia, FAS -670AG could be interpreted to mean that this genotype provides protection against idiopathic azoospermia. The study of combined genotype and haplotype frequencies has found statistically significant differences between case and control subjects for some combinations. The AA-GG binary genotype for the FAS670 and FAS1377 loci couple, in particular, may have a high degree of predisposition to idiopathic azoospermia. Our results suggest that FAS -670A/G SNP may be a genetic predisposing factor of idiopathic azoospermia among southeastern Anatolian men. Larger studies are needed to verify these findings. Furthermore, our data indicated a possible linkage between the FAS and FASLG genes and idiopathic azoospermia.

75 FR 57778 - Issuance of an Experimental Use Permit

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-22

...) necessary for its production in Event TC1507 corn. There are 10.213 kilograms (kg) of eCry3.1Ab, 11.14 grams of Cry1Ab, 8,145 grams of Cry34Ab1, 112.1 grams of Cry35Ab1, 280.6 grams of Vip3Aa20, 217.9 grams of mCry3A, and 177.5 grams of Cry1F proteins in 69,473 kg seeds on 7,311 acres (3,830 PIP and 3,481 non...

[Effect of TNF-alpha gene polymorphism on outcome of thalidomide-based regimens for multiple myeloma].

PubMed

DU, Juan; Yuan, Zhen-Gang; Zhang, Chun-Yang; Fu, Wei-Jun; Jiang, Hua; Chen, Bao-An; Hou, Jian

2009-10-01

To evaluate the effect of polymorphism at the -238 and -308 position of the TNF-alpha promotor region on the clinical outcome of thalidomide (Thal)-based regimens for the treatment of multiple myeloma (MM). The polymorphism at the -238 and -308 position of the TNF-alpha promotor region of 168 MM patients treated with Thal-based regimens were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotypes were tested for association with overall response by logistic regression, and survival was evaluated by univariate and multivariate analysis. In TNF-alpha -238 position, 11 (6.5%) patients had GA genotype and 1 (0.6%) AA genotype. In TNF-alpha -308 position, 19 (11.3%) had GA genotype and 1 (0.6%) AA genotype. In univariate analysis, the TNF-alpha -238 GA + AA genotypes were associated with a significantly prolonged progression free survival (PFS) (P = 0.017), and a better overall survival (OS) (P = 0.150). Multivariate COX regression analysis showed that TNF-alpha -238 polymorphic status was an independent prognostic factor for prolonged PFS (P = 0.049). The TNF-alpha -238 polymorphic status is associated with a favorable clinical outcome in MM patients treated with thalidomide-based regimen. The polymorphism status of TNF-alpha gene might be of promise for developing a more informative stratification system for MM.

Polymorphisms of the myostatin gene and its relationship with reproduction traits in the Bian chicken.

PubMed

Zhang, Genxi; Zhang, Li; Wei, Yue; Wang, Jinyu; Ding, Fuxiang; Dai, Guojun; Xie, Kaizhou

2012-01-01

Myostatin, or growth and differentiation factor 8, is a member of the transforming growth factor-β superfamily; it functions as a negative regulator of skeletal muscle development and growth in mammals. In this study, single nucleotide polymorphisms in the 5' regulatory region and exon 1 of the myostatin gene were detected by PCR-SSCP in the Bian, Jinghai, Youxi, and Arbor Acre chickens, and the associations of the polymorphisms with reproduction traits were analyzed. Seven SNPs (A326G, C334G, C1346T, G1375A, A1473G, G1491A, and G2283A) were found in the myostatin gene. Association analysis showed that the G2283A were significantly associated with reproduction traits. Bian chickens of the GG genotype had a greater age at first egg than those of the GA and AA genotypes (P<0.01). Correspondingly, Bian chickens of the GA and AA genotypes had larger egg number at 300 days than those of the GG genotype (P<0.05 and P<0.01, respectively). Bian chickens of the AA genotype had significantly higher body weight at 300 days than those of the GG genotype (P<0.05). These results suggested that the myostatin gene may have certain effects on reproduction traits other than merely as a negative regulator of skeletal muscle development and growth in mammals previously reported.

[CYP7A1 gene polymorphism and the characteristics of dyslipidemias in patients with nonalcoholic fatty liver disease concurrent with hypothyroidism].

PubMed

Zhaldak, D A; Melekhovets, O K; Orlovskyi, V F

To investigate the association of the polymorphic variants -204A > C (rs 3808607) in the CYP7A1 gene with the development of dyslipidemias in healthy individuals, in patients with non-alcoholic fatty liver disease (NAFLD) and in those with NAFLD concurrent with hypothyroidism. DNA samples and lipidograms were examined in 180 patients, including 60 healthy individuals (Group 1), 60 patients with hypothyroidism concurrent with NAFLD (Group 2), and 60 patients with NAFLD (Group 3). All the patients underwent ultrasound examination of the thyroid gland and abdominal cavity organs; FibroMax scores were calculated. All the study groups most frequently showed a homozygous AA genotype (86.6% of cases in Group 1, 80% in Group 2, and 83.3% in Group 3). The development of NAFLD in CC genotype carriers is characterized by the most pronounced changes in lipid metabolism (atherogenic index (AI), 7.32 in Group 3) compared to the genotypes AA (AI, 4.56 in Group 2 and 1.73 in Group 1) and CC (AI, 6.43 in Group 2 and 2.52 in Group 1) in functional insufficiency of thyroid hormones and relative normal conditions. The analysis of the relationship of polymorphic variants CYP7A1 rs 38088607 to lipid metabolic disturbances in the study groups showed that the significantly higher levels of atherogenic cholesterol fractions were determined in the CC genotype compared to AA genotype carriers and they did not depend on the presence of NAFLD and hypothyroidism. The findings make it possible to consider the AA homozygous genotype of variant mutation CYP7A1 rs 38088607 as protective against dyslipidemia. However, in functional insufficiency of thyroid hormones, the level of triglycerides is significantly higher in both genotypes, which suggests that hypothyroidism plays an essential role in the development of dyslipidemia and NAFLD.

Coexistence of the 677C>T and 1298A>C MTHFR polymorphisms and its significance in the population of Polish women.

PubMed

Wolski, Hubert; Kocięcka, Maria; Mrozikiewicz, Aleksandra E; Barlik, Magdalena; Kurzawińska, Grażyna

2015-10-01

The aim of the study was to evaluate the frequency of the 677C>T and 1298A>C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene, as well as the coexistence of both these genetic variants in women from the Polish population. A total of 662 women from the Polish population were enrolled in the study group. The frequency of the investigated genotypes of the 677C>T and 1298A>C polymorphisms of the MTHFR gene was analyzed with the use of PCR/RFLP methods. The frequency of the 677CC, 677CT and 677TT genotypes in the studied population of women was 50.60%, 39.88% and 9.52%, respectively As to the 1298AA, 1298AC and 1298CC genotypes, the obtained results were as follows: 42.75%, 47.88% and 9.37%, respectively (Tables II and III). Simultaneous analysis revealed the most frequent coexistence of 677CC/1298AC (28.85%), 677CT/1298AA (20.85%) and 677CT/1298AC (19.03%) genotypes. The coexistence of 677CC/1298AA (12.39%), 677CC/1298CC (9.37%) and 677TT/1298AA (9.51%) genotypes was observed less frequently In the studied population of Polish women, the coexistence of 677CT/1298CC, 677TT/1298AC and 677TT/1298CC genotypes has been not observed. The frequency and coexistence of genotypes of the 677C>T and 1298A>C MTHFR gene polymorphisms in the studied population of Polish women is similar to other North-European populations. Women carriers of the mutated variants of both, 677C>T and 1298A>C polymorphisms of the MTHFR gene should receive special perinatal care in order to prevent fetal defects and thrombosis-related complications during pregnancy It is vital to emphasize the significance of proper education of folate supplementation, especially in pregnant patients and women of reproductive age.

The association of variants in the FTO gene with longitudinal body mass index profiles in non-Hispanic white children and adolescents.

PubMed

Hallman, D M; Friedel, V C; Eissa, M A H; Boerwinkle, E; Huber, J C; Harrist, R B; Srinivasan, S R; Chen, W; Dai, S; Labarthe, D R; Berenson, G S

2012-01-01

To investigate possible age-related changes in associations between polymorphisms in the fat mass and obesity-associated (FTO) gene and higher body mass index (BMI). Multilevel mixed regression models were used to examine associations between four FTO variants and longitudinal BMI profiles in non-Hispanic white and African American children and adolescents 8-17 years of age from two different longitudinal cohort studies, the Bogalusa Heart Study (BHS) and Project HeartBeat! (PHB). In the BHS, there were 1551 examinations of 478 African Americans and 3210 examinations of 1081 non-Hispanic whites; in PHB, there were 971 examinations of 131 African Americans and 4458 examinations of 505 non-Hispanic whites. In African Americans, no significant FTO associations with BMI were found. In non-Hispanic whites, linkage disequilibrium among all four variants made haplotype analysis superfluous, so we focused on the single-nucleotide polymorphism, rs9939609. In longitudinal multilevel models, the A/A genotype of rs9939609 was associated with higher BMI in non-Hispanic whites in both cohorts at all ages. A significant age-by-genotype interaction found only in the BHS cohort predicted that in those with the A/A genotype, BMI would be ∼0.7 kg m(-2) higher at age 8 and ∼1.6 kg m(-2) higher at age 17 than in those with A/T or T/T genotypes. The design of PHB limited follow-up of any single individual to 4 years, and may have reduced the ability to detect any age-by-genotype interaction in this cohort. The A/A genotype of rs9939609 in the FTO gene is associated with higher longitudinal BMI profiles in non-Hispanic whites from two different cohorts. The association may change with age, with the A/A genotype being associated with a larger BMI difference in late adolescence than in childhood, though this was observed only in the BHS cohort and requires verification.

[Genetic polymorphism of the IL8 gene and its associations with milk traits and SCS in Chinese Holstein].

PubMed

Chen, Ren-Jin; Yang, Zhang-Ping; Mao, Yong-Jiang; Chen, Ying; Chang, Ling-Ling; Ji, De-Jun; Wu, Hai-Tao; Li, Yun-Long; Li, Rui

2010-12-01

The polymorphism of Interleukin-8 (IL8) gene were investigated for 610 Chinese Holstein cows of 30 bull families from a dairy farm in Shanghai using Polymerase Chain Reaction-Single Strand Conformation Polymorphism (PCR-SSCP) technique with a mixed animal model to verify the effects of the polymorphisms on some milk productive performance, tested day milk yield, tested day fat percentage, tested day milk protein percentage, 305 d corrected milk yield, 305 d milk fat yield, 305 d milk protein yield, and somatic cell score (SCS). The aim was to explore the significant molecular marker in practical dairy production. Three genotypes were identified and the genotypic frequencies of KK, KA, and AA were 0.187, 0.451, and 0.362, respectively. The gene frequencies of K and A were 0.412 and 0.588. The results showed highly significant (P < 0.01) association of IL8 mutations with tested day milk yield, 305 d milk protein yield, 305 d corrected milk yield and 305 d milk fat yield, SCS and tested day milk protein percentage (P < 0.05). However, no association (P > 0.05) with tested day milk fat percentage was recorded. The cows with KK genotype had higher tested day milk yield, 305 d milk protein yield, 305 d corrected milk yield and 305 d milk fat yield than those with AA and KA genotypes (P < 0.01). The least square mean of SCS for KK was significantly lower than that with AA and KA genotypes (P < 0.01). AA genotype was significant lower in tested day milk protein percentage than KK and KA genotypes (P < 0.05). The IL8 gene genetic diversity has a great genetic effect on milk traits and mastitis resistance and could be a useful genetic marker for Chinese Holstein breeding.

GABBR1 and SLC6A1, two genes involved in modulation of GABA synaptic transmission influence risk for alcoholism; results from three ethnically diverse populations

PubMed Central

Enoch, Mary-Anne; Hodgkinson, Colin A.; Shen, Pei-Hong; Gorodetsky, Elena; Marietta, Cheryl A.; Roy, Alex; Goldman, David

2015-01-01

Background Animal and human studies indicate that GABBR1, encoding the GABAB1 receptor subunit, and SLC6A1, encoding the neuronal GABA transporter GAT1, play a role in addiction by modulating synaptic GABA. Therefore variants in these genes might predict risk/resilience for alcoholism. Methods This study included three populations that differed by ethnicity and alcoholism phenotype: African American (AA) men: 401 treatment-seeking inpatients with single/comorbid diagnoses of alcohol and drug dependence, 193 controls; Finnish Caucasian men: 159 incarcerated alcoholics, half with comorbid ASPD, 181 controls; a community sample of Plains Indian (PI) men and women: 239 alcoholics, 178 controls. Seven GABBR1 tag SNPs were genotyped in the AA and Finnish samples; rs29220 was genotyped in the PI for replication. Also, a uniquely African, functional SLC6A1 insertion promoter polymorphism (IND) was genotyped in the AAs. Results We found a significant and congruent association between GABBR1 rs29220 and alcoholism in all three populations. The major genotype (heterozygotes in AAs, Finns) and the major allele in PIs were significantly more common in alcoholics. Moreover, SLC6A1 IND was more abundant in controls, i.e. the major genotype predicted alcoholism. An analysis of combined GABBR1 rs29220 and SLC6A1 IND genotypes showed that rs29220 heterozygotes, irrespective of their IND status, had an increased risk for alcoholism whereas carriers of the IND allele and either rs29220 homozygote were more resilient. Conclusions Our results show that with both GABBR1 and SLC6A1, the minor genotypes/alleles were protective against risk for alcoholism. Finally, GABBR1 rs29220 might predict treatment response/adverse effects for baclofen, a GABAB receptor agonist. PMID:26727527

Association between CYP19 gene SNP rs2414096 polymorphism and polycystic ovary syndrome in Chinese women.

PubMed

Jin, Jia-Li; Sun, Jing; Ge, Hui-Juan; Cao, Yun-Xia; Wu, Xiao-Ke; Liang, Feng-Jing; Sun, Hai-Xiang; Ke, Lu; Yi, Long; Wu, Zhi-Wei; Wang, Yong

2009-12-16

Several studies have reported the association of the SNP rs2414096 in the CYP19 gene with hyperandrogenism, which is one of the clinical manifestations of polycystic ovary syndrome (PCOS). These studies suggest that SNP rs2414096 may be involved in the etiopathogenisis of PCOS. To investigate whetherthe CYP19 gene SNP rs2414096 polymorphism is associated with the susceptibility to PCOS, we designed a case-controlled association study including 684 individuals. A case-controlled association study including 684 individuals (386 PCOS patients and 298 controls) was performed to assess the association of SNP rs2414096 with PCOS. Genotyping of SNP rs2414096 was conducted by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method that was performed on genomic DNA isolated from blood leucocytes. Results were analyzed in respect to clinical test results. The genotypic distributions of rs2414096 (GG, AG, AA) in the CYP19 gene (GG, AG, AA) in women with PCOS (0.363, 0.474, 0.163, respectively) were significantly different from that in controls (0.242, 0.500, 0.258, respectively) (P = 0.001). E2/T was different between the AA and GG genotypes. Age at menarche (AAM) and FSH were also significantly different among the GG, AG, and AA genotypes in women with PCOS (P = 0.0391 and 0.0118, respectively). No differences were observed in body mass index (BMI) and other serum hormone concentrations among the three genotypes, either in the PCOS patients or controls. Our data suggest that SNP rs2414096 in the CYP19 gene is associated with susceptibility to PCOS.

Low density lipoprotein receptor gene Ava II polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations

PubMed Central

2011-01-01

Background Several common genetic polymorphisms in the low density lipoprotein receptor (LDL-R) gene have associated with modifications of serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels, but the results are not consistent in different populations. Bai Ku Yao is a special subgroup of the Yao minority in China. The present study was undertaken to detect the association of LDL-R gene Ava Ⅱ polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations. Methods A total of 1024 subjects of Bai Ku Yao and 792 participants of Han Chinese were randomly selected from our previous stratified randomized cluster samples. Genotyping of the LDL-R gene Ava Ⅱ polymorphism was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Results The levels of serum TC, high density lipoprotein cholesterol (HDL-C), LDL-C, apolipoprotein (Apo) A1 and the ratio of ApoA1 to ApoB were lower in Bai Ku Yao than in Han (P < 0.01 for all). The frequency of A- and A+ alleles was 65.5% and 34.5% in Bai Ku Yao, and 80.7% and 19.3% in Han (P < 0.001); respectively. The frequency of A-A-, A-A+ and A+A+ genotypes was 42.6%, 45.9% and 11.5% in Bai Ku Yao, and 64.9%, 31.6% and 3.5% in Han (P < 0.001); respectively. There was also significant difference in the genotypic frequencies between males and females in Bai Ku Yao (P <0.05), and in the genotypic and allelic frequencies between normal LDL-C (≤ 3.20 mmol/L) and high LDL-C (>3.20 mmol/L) subgroups in Bai Ku Yao (P < 0.05 for each) and between males and females in Han (P < 0.05 for each). The levels of LDL-C in males and TC and HDL-C in females were different among the three genotypes (P < 0.05 for all) in Bai Ku Yao, whereas the levels of HDL-C in males and HDL-C and ApoA1 in females were different among the three genotypes (P < 0.05-0.001) in Han. The subjects with A+A+ genotype had higher serum LDL-C, TC, HDL-C or ApoA1 levels than the subjects with A-A+ and A-A- genotypes. Spearman rank correlation analysis revealed that the levels of LDL-C in Bai Ku Yao and HDL-C in Han were correlated with genotypes (P < 0.05 and P < 0.01; respectively). Conclusions The association of LDL-R gene Ava Ⅱ polymorphism and serum lipid levels is different between the Bai Ku Yao and Han populations. The discrepancy might partly result from different LDL-R gene Ava Ⅱ polymorphism or LDL-R gene-enviromental interactions. PMID:21345210

Acrylonitrile removal from synthetic wastewater and actual industrial wastewater with high strength nitrogen using a pure bacteria culture.

PubMed

Wang, C C; Lee, C M; Cheng, P W

2001-01-01

A gram-negative rod-shaped bacteria (strain AAS6), capable of utilizing acrylonitrile as the sole source of both carbon and nitrogen, was utilized to investigate the removal of acrylonitrile in ABS resin manufacturing wastewater. Both synthetic wastewater, containing a high concentration of acrylonitrile, and actual wastewater obtained from an ABS manufacturing factory were used. The result indicated that strain AAS6 was capable of completely removing acrylonitrile from synthetic wastewater containing less than 889 mg/l acrylonitrile and from actual industrial wastewater containing less than 400 mg/l acrylonitrile. Whether in synthetic wastewater or actual industrial wastewater, strain AAS6 showed approximately the same ability for acrylonitrile removal and used acrylic acid, a metabolic by-product of acrylonitrile, as the carbon source and ammonium as the nitrogen source. The bacteria could not directly metabolize other chemicals found in the actual industrial wastewater. However, its metabolic activities were not inhibited by the presence of compounds such as butadiene, styrene or acrylonitrile-styrene polymer. Thus, this strain is expected to play an important role in aeration tanks for treating ABS resin manufacturing wastewater.

Dynamical mass measurement of the young spectroscopic binary V343 Normae AaAb resolved with the Gemini Planet Imager

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nielsen, Eric L.; De Rosa, Robert J.; Wang, Jason

Here, we present new spatially resolved astrometry and photometry from the Gemini Planet Imager of the inner binary of the young multiple star system V343 Normae, which is a member of the β Pictoris (β Pic) moving group. V343 Normae comprises a K0 and mid-M star in a ~4.5 year orbit (AaAb) and a wide 10'' M5 companion (B). By combining these data with archival astrometry and radial velocities we fit the orbit and measure individual masses for both components ofmore » $${M}_{\\mathrm{Aa}}=1.10\\pm 0.10\\,{M}_{\\odot }$$ and $${M}_{\\mathrm{Ab}}=0.290\\pm 0.018\\,{M}_{\\odot }$$. Comparing to theoretical isochrones, we find good agreement for the measured masses and JHK band magnitudes of the two components consistent with the age of the β Pic moving group. We derive a model-dependent age for the β Pic moving group of 26 ± 3 Myr by combining our results for V343 Normae with literature measurements for GJ 3305, which is another group member with resolved binary components and dynamical masses.« less

Transition metal intercalated bilayer silicene

NASA Astrophysics Data System (ADS)

Pandey, Dhanshree; Kamal, C.; Chakrabarti, Aparna

2018-04-01

We investigate the electronic and magnetic properties of Mn, Fe and Co-intercalated silicene bilayer with AA and AB stacking by using spin polarized density functional theory. The intercalation of Mn increases the gap between the two layers of silicene due to the larger atomic radii of Mn as compared to Fe and Co. Bader charge analysis has been performed to understand the bonding between the TM and Si atoms. This also helps in explaining the magnetic moment possessed by the composite systems after intercalating TM in between the layers of bilayer silicene system. This study reveals that a significant net magnetic moment is observed in cases of Mn-intercalated silicene bilayers, whereas Fe has a very small moment of 0.78 µB in the case of AA stacking configuration only. Co intercalation leads to net zero magnetic moment. Further, we find that Fe and Co marginally favor the AB stacking whereas Mn has a slight preference of the AA over the AB configuration. The composite systems, specifically when intercalated with Fe and Co atoms, favor a hybridization which is far away from sp3-like hybridization along the plane of Si atoms in bilayer silicene.

Dynamical mass measurement of the young spectroscopic binary V343 Normae AaAb resolved with the Gemini Planet Imager

DOE PAGES

Nielsen, Eric L.; De Rosa, Robert J.; Wang, Jason; ...

2016-11-22

Here, we present new spatially resolved astrometry and photometry from the Gemini Planet Imager of the inner binary of the young multiple star system V343 Normae, which is a member of the β Pictoris (β Pic) moving group. V343 Normae comprises a K0 and mid-M star in a ~4.5 year orbit (AaAb) and a wide 10'' M5 companion (B). By combining these data with archival astrometry and radial velocities we fit the orbit and measure individual masses for both components ofmore » $${M}_{\\mathrm{Aa}}=1.10\\pm 0.10\\,{M}_{\\odot }$$ and $${M}_{\\mathrm{Ab}}=0.290\\pm 0.018\\,{M}_{\\odot }$$. Comparing to theoretical isochrones, we find good agreement for the measured masses and JHK band magnitudes of the two components consistent with the age of the β Pic moving group. We derive a model-dependent age for the β Pic moving group of 26 ± 3 Myr by combining our results for V343 Normae with literature measurements for GJ 3305, which is another group member with resolved binary components and dynamical masses.« less

IL-1B rs16944 polymorphism is related to septic shock and death.

PubMed

Jiménez-Sousa, María Ángeles; Medrano, Luz M; Liu, Pilar; Almansa, Raquel; Fernández-Rodríguez, Amanda; Gómez-Sánchez, Esther; Rico, Lucía; Heredia-Rodríguez, María; Gómez-Pesquera, Estefanía; Tamayo, Eduardo; Resino, Salvador

2017-01-01

IL-1β is a primary mediator of systemic inflammatory response syndrome (SIRS) and it may lead to shock septic. Our aim was to analyse whether IL-1B rs16944 polymorphism is associated with the onset of septic shock and death after major surgery. We performed a case-control study on 467 patients who underwent major cardiac or abdominal surgery. Of them, 205 patients developed septic shock (cases, SS group) and 262 patients developed SIRS (controls, SIRS group). The primary outcome variables were the development of septic shock and death within 90 days after diagnosis of septic shock. The IL-1B rs16944 polymorphism was genotyped by Sequenom's MassARRAY platform. The association analysis was performed under a recessive genetic model (AA vs. GG/GC). The frequency of septic shock was higher in patients with IL-1B rs16944 AA genotype than in patients with IL-1B rs16944 GG/AG genotype when all patients were taken into account (63·6% vs. 41·8%; P = 0·006), cardiac surgery (52·2% vs. 33·3%; P = 0·072) and abdominal surgery (76·2% vs. 50·2%; P = 0·023). However, the IL-1B rs16944 AA genotype was only associated with higher likelihood of septic shock in the analysis of all population [adjusted odds ratio (aOR) = 2·26 (95%CI = 1·03; 4·97; P = 0·042], but not when it was stratified by cardiac surgery (P = 0·175) or abdominal surgery (P = 0·467). Similarly, IL-1B rs16944 AA genotype was also associated with higher likelihood of septic shock-related death in all population [aOR = 2·67 (95%CI = 1·07; 4·97); P = 0·035]. IL-1B rs16944 AA genotype seems to be related to the onset of septic shock and death in patients who underwent major surgery. © 2016 Stichting European Society for Clinical Investigation Journal Foundation.

75 FR 3234 - Issuance of an Experimental Use Permit

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-20

... The quantity authorized equates to 68,066 pounds of corn seed [containing 62 grams (0.137 pounds) of Cry1F protein, 787 grams (1.74 pounds) of Cry34Ab1 and Cry35Ab1 proteins, 27 grams (0.060 pounds) of Cry1Ab protein, 347 grams (0.765 pounds) of Vip3Aa20 protein, and 11 grams (0.024 pounds) of mCry3A...

Exploration of the utility of ancestry informative markers for genetic association studies of African Americans with type 2 diabetes and end stage renal disease.

PubMed

Keene, Keith L; Mychaleckyj, Josyf C; Leak, Tennille S; Smith, Shelly G; Perlegas, Peter S; Divers, Jasmin; Langefeld, Carl D; Freedman, Barry I; Bowden, Donald W; Sale, Michèle M

2008-09-01

Admixture and population stratification are major concerns in genetic association studies. We wished to evaluate the impact of admixture using empirically derived data from genetic association studies of African Americans (AA) with type 2 diabetes (T2DM) and end-stage renal disease (ESRD). Seventy ancestry informative markers (AIMs) were genotyped in 577 AA with T2DM-ESRD, 596 AA controls, 44 Yoruba Nigerian (YRI) and 39 European American (EA) controls. Genotypic data and association results for eight T2DM candidate gene studies in our AA population were included. Ancestral estimates were calculated using FRAPPE, ADMIXMAP and STRUCTURE for all AA samples, using varying numbers of AIMs (25, 50, and 70). Ancestry estimates varied significantly across all three programs with the highest estimates obtained using STRUCTURE, followed by ADMIXMAP; while FRAPPE estimates were the lowest. FRAPPE estimates were similar using varying numbers of AIMs, while STRUCTURE estimates using 25 AIMs differed from estimates using 50 and 70 AIMs. Female T2DM-ESRD cases showed higher mean African proportions as compared to female controls, male cases, and male controls. Age showed a weak but significant correlation with individual ancestral estimates in AA cases (r2 = 0.101; P = 0.019) and in the combined set (r2 = 0.131; P = 3.57 x 10(-5)). The absolute difference between frequencies in parental populations, absolute delta, was correlated with admixture impact for dominant, additive, and recessive genotypic models of association. This study presents exploratory analyses of the impact of admixture on studies of AA with T2DM-ESRD and supports the use of ancestral proportions as a means of reducing confounding effects due to admixture.

Exploration of the utility of ancestry informative markers for genetic association studies of African Americans with type 2 diabetes and end stage renal disease

PubMed Central

Keene, Keith L.; Mychaleckyj, Josyf C.; Leak, Tennille S.; Smith, Shelly G.; Perlegas, Peter S.; Divers, Jasmin; Langefeld, Carl D.; Freedman, Barry I.; Bowden, Donald W.; Sale, Michèle M.

2009-01-01

Admixture and population stratification are major concerns in genetic association studies. We wished to evaluate the impact of admixture using empirically derived data from genetic association studies of African Americans (AA) with type 2 diabetes (T2DM) and end-stage renal disease (ESRD). Seventy ancestry informative markers (AIMs) were genotyped in 577 AA with T2DM-ESRD, 596 AA controls, 44 Yoruba Nigerian (YRI) and 39 European American (EA) controls. Genotypic data and association results for eight T2DM candidate gene studies in our AA population were included. Ancestral estimates were calculated using FRAPPE, ADMIXMAP and STRUCTURE for all AA samples, using varying numbers of AIMs (25, 50, and 70). Ancestry estimates varied significantly across all three programs with the highest estimates obtained using STRUCTURE, followed by ADMIXMAP; while FRAPPE estimates were the lowest. FRAPPE estimates were similar using varying numbers of AIMs, while STRUCTURE estimates using 25 AIMs differed from estimates using 50 and 70 AIMs. Female T2DM-ESRD cases showed higher mean African proportions as compared to female controls, male cases, and male controls. Age showed a weak but significant correlation with individual ancestral estimates in AA cases (r2=0.101; P=0.019) and in the combined set (r2=0.131; P=3.57×10−5). The absolute difference between frequencies in parental populations, absolute δ, was correlated with admixture impact for dominant, additive, and recessive genotypic models of association. This study presents exploratory analyses of the impact of admixture on studies of AA with T2DM-ESRD and supports the use of ancestral proportions as a means of reducing confounding effects due to admixture. PMID:18654799

Resistance of different stocks and transferrin genotypes of coho salmon, Oncorhynchus kisutch, and steelhead trout, Salmo gairdneri, to bacterial kidney disease and vibriosis

USGS Publications Warehouse

Winter , Gary W.; Schreck, Carl B.; McIntyre, John D.

1979-01-01

Juvenile coho salmon and steelhead trout ofdifferentstocks and three transferrin genotypes(AA, AC, and CCl, all reared in identical or similar environments, were experimentally infected with Corynebacterium sp., the causative agent ofbacterial kidney disease, or with Vibrio anguillarum, the causative agent of vibriosis. Mortality due to the pathogens was compared among stocks within a species and among transferrin genotypes within a stock to determine whetherthere was a geneticbasis for resistance to disease. Differences in resistance to bacterial kidney disease among coho salmon stocks had a genetic basis. Stock susceptibility to vibriosis was strongly influenced by environmental factors. Coho salmon orsteelhead trout of one stock may be resistant to one disease but susceptible to another. The importance of transferrin genotype of coho salmon in resistance to bacterial kidney disease was stock specific; in stocks that showed differential resistance of genotypes, the AA was the most susceptible. No differencesin resistance to vibriosis were observed among transferrin genotypes.

Comprehensive Analysis and Characterization of Linear Antigenic Domains on HN Protein from Genotype VII Newcastle Disease Virus Using Yeast Surface Display System

PubMed Central

Li, Tao; Wang, Gaoling; Shi, Bingtian; Liu, Peixin; Si, Wei; Wang, Bin; Jiang, Li; Zhou, Lunjiang; Xiu, Jinsheng; Liu, Henggui

2015-01-01

Circulation of genotype VII Newcastle disease virus (NDV) has posed a great threat for the poultry industry worldwide. Antibodies against Hemagglutinin-neuraminidase (HN), a membrane protein of NDV with critical roles in NDV infection, have been reported to provide chickens protection from NDV infection. In this study, we comprehensively analyzed the in vivo antibody responses against the linear antigenic domains of the HN protein from genotype VII NDV using a yeast surface display system. The results revealed four distinct regions of HN, P1 (1-52aa), P2 (53-192aa), P3 (193-302aa) and P4 (303-571aa), respectively, according to their antigenic potency. Analysis by FACS and ELISA assay indicated P2 to be the dominant linear antigenic domain, with the immunogenic potency to protect the majority of chickens from NDV challenge. In contrast, the P1, P3 and P4 domains showed weak antigenicity in vivo and could not protect chickens from NDV challenge. These results provide important insight into the characteristic of humoral immune responses elicited by HN of NDV in vivo. PMID:26121247

Analysis of hepatitis B virus preS1 variability and prevalence of the rs2296651 polymorphism in a Spanish population

PubMed Central

Casillas, Rosario; Tabernero, David; Gregori, Josep; Belmonte, Irene; Cortese, Maria Francesca; González, Carolina; Riveiro-Barciela, Mar; López, Rosa Maria; Quer, Josep; Esteban, Rafael; Buti, Maria; Rodríguez-Frías, Francisco

2018-01-01

AIM To determine the variability/conservation of the domain of hepatitis B virus (HBV) preS1 region that interacts with sodium-taurocholate cotransporting polypeptide (hereafter, NTCP-interacting domain) and the prevalence of the rs2296651 polymorphism (S267F, NTCP variant) in a Spanish population. METHODS Serum samples from 246 individuals were included and divided into 3 groups: patients with chronic HBV infection (CHB) (n = 41, 73% Caucasians), patients with resolved HBV infection (n = 100, 100% Caucasians) and an HBV-uninfected control group (n = 105, 100% Caucasians). Variability/conservation of the amino acid (aa) sequences of the NTCP-interacting domain, (aa 2-48 in viral genotype D) and a highly conserved preS1 domain associated with virion morphogenesis (aa 92-103 in viral genotype D) were analyzed by next-generation sequencing and compared in 18 CHB patients with viremia > 4 log IU/mL. The rs2296651 polymorphism was determined in all individuals in all 3 groups using an in-house real-time PCR melting curve analysis. RESULTS The HBV preS1 NTCP-interacting domain showed a high degree of conservation among the examined viral genomes especially between aa 9 and 21 (in the genotype D consensus sequence). As compared with the virion morphogenesis domain, the NTCP-interacting domain had a smaller proportion of HBV genotype-unrelated changes comprising > 1% of the quasispecies (25.5% vs 31.8%), but a larger proportion of genotype-associated viral polymorphisms (34% vs 27.3%), according to consensus sequences from GenBank patterns of HBV genotypes A to H. Variation/conservation in both domains depended on viral genotype, with genotype C being the most highly conserved and genotype E the most variable (limited finding, only 2 genotype E included). Of note, proline residues were highly conserved in both domains, and serine residues showed changes only to threonine or tyrosine in the virion morphogenesis domain. The rs2296651 polymorphism was not detected in any participant. CONCLUSION In our CHB population, the NTCP-interacting domain was highly conserved, particularly the proline residues and essential amino acids related with the NTCP interaction, and the prevalence of rs2296651 was low/null. PMID:29456407

IGF-I receptor 275124A>C (rs1464430) polymorphism and athletic performance.

PubMed

Ben-Zaken, Sigal; Meckel, Yoav; Nemet, Dan; Eliakim, Alon

2015-05-01

To examine the prevalence of the Insulin-Like Growth Factor-I receptor (IGF-IR) 275124A>C polymorphism, known to be associated with exercise-related cardiac hypertrophy, among elite endurance and power athletes. One hundred and fifty-nine athletes (118 men and 41 women, age: 35.9±12.2 yrs) participated in the study. We hypothesized that presence of the A allele will be significantly more common among endurance athletes (n=77) compared to power athletes (n=82) and non-physically active controls (n=68). Athletes within each group were further divided according to their individual best performance into elite athletes (those who had represented the country in international track-and-field or triathlon competitions or in the Olympic Games) and national-level athletes. The prevalence of the AA genotype was significantly higher (p<0.05) in the endurance athletes group (49%) compared to the power athletes group (33%), but did not differ from the control group (46%). There was no significant difference in the prevalence of the AA genotype between elite and national level endurance athletes (44% versus 52%, respectively). In contrast, among power athletes, the prevalence of the AA genotype was significantly lower in the elite compared to national level athletes (17% versus 42%, respectively; p<0.05). The results of the present study may suggest that the IGF-IR AA polymorphism is beneficial for endurance-type sports, but is not associated with elite endurance performance. In contrast, the presence of the AA genotype may be a disadvantage in power sports. All together the results of the present study suggest that IGF-IR polymorphism may differentiate between the two edges of the endurance-power athletic performance spectrum. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

The Gln32Lys polymorphism in HSP22 of Zhikong scallop Chlamys farreri is associated with heat tolerance.

PubMed

Yang, Chuanyan; Zhang, Lei; Wang, Lingling; Zhang, Huan; Qiu, Limei; Siva, Vinu S; Song, Linsheng

2011-01-01

Heat shock protein 22 is a member of small heat shock proteins with molecular chaperone activity. Though their multiple functions have been well characterized, there is no report about the association between the polymorphisms of HSP22 and heat tolerance. Three single nucleotide polymorphisms were identified in HSP22 from scallop Chlamys farreri (CfHSP22), and the +94 C-A locus was found to be nonsynonymous. Three genotypes at locus +94, A/A, A/C and C/C, were revealed by using Bi-PASA PCR analysis, and their frequencies were 19.5%, 27.6% and 52.9% in the heat resistant stock, while 9.3%, 17.4% and 73.3% in the heat susceptible stock, respectively. The frequency differences of the three genotypes were significant (P<0.05) between the two stocks. After incubating at 30°C for 84 h, the cumulative mortality of scallops with +94 C/C genotype and +94 A/C genotypes was 95% and 90%, respectively, which was significantly higher (P<0.01) than that of scallops with +94 A/A genotype (70%). The molecular chaperone activity of two His-tagged fusion proteins, rCfHSP22Q with +94 C/C genotype and rCfHSP22K with +94 A/A genotype were analyzed by testing the ability of protecting citrate synthase (CS) against thermal inactivation in vitro. After incubated with rCfHSP22Q or rCfHSP22K at 38°C for 1 h, the activity of CS lost 50% and 45%, and then recovered to 89% and 95% of the original activity following 1 h restoration at 22°C, respectively, indicating that the mutation from Gln to Lys at this site might have an impact on molecular chaperone activities of CfHSP22. These results implied that the polymorphism at locus +94 of CfHSP22 was associated with heat tolerance of scallop, and the +94 A/A genotype could be a potential marker available in future selection of Zhikong scallop with heat tolerance.

Phage display antibodies against ectromelia virus that neutralize variola virus: Selection and implementation for p35 neutralizing epitope mapping.

PubMed

Khlusevich, Yana; Matveev, Andrey; Baykov, Ivan; Bulychev, Leonid; Bormotov, Nikolai; Ilyichev, Ivan; Shevelev, Georgiy; Morozova, Vera; Pyshnyi, Dmitrii; Tikunova, Nina

2018-04-01

In this study, five phage display antibodies (pdAbs) against ectromelia virus (ECTV) were selected from vaccinia virus (VACV)-immune phage-display library of human single chain variable fragments (scFv). ELISA demonstrated that selected pdAbs could recognize ECTV, VACV, and cowpox virus (CPXV). Atomic force microscopy visualized binding of the pdAbs to VACV. Three of the selected pdAbs neutralized variola virus (VARV) in the plaque reduction neutralization test. Western blot analysis of ECTV, VARV, VACV, and CPXV proteins indicated that neutralizing pdAbs bound orthopoxvirus 35 kDa proteins, which are encoded by the open reading frames orthologous to the ORF H3L in VACV. The fully human antibody fh1A was constructed on the base of the VH and VL domains of pdAb, which demonstrated a dose-dependent inhibition of plaque formation after infection with VARV, VACV, and CPXV. To determine the p35 region responsible for binding to neutralizing pdAbs, a panel of truncated p35 proteins was designed and expressed in Escherichia coli cells, and a minimal p35 fragment recognized by selected neutralizing pdAbs was identified. In addition, peptide phage-display combinatorial libraries were applied to localize the epitope. The obtained data indicated that the epitope responsible for recognition by the neutralizing pdAbs is discontinuous and amino acid residues located within two p35 regions, 15-19 aa and 232-237 aa, are involved in binding with neutralizing anti-p35 antibodies. Copyright © 2018. Published by Elsevier B.V.

Broad blockade antibody responses in human volunteers after immunization with a multivalent norovirus VLP candidate vaccine: immunological analyses from a phase I clinical trial.

PubMed

Lindesmith, Lisa C; Ferris, Martin T; Mullan, Clancy W; Ferreira, Jennifer; Debbink, Kari; Swanstrom, Jesica; Richardson, Charles; Goodwin, Robert R; Baehner, Frank; Mendelman, Paul M; Bargatze, Robert F; Baric, Ralph S

2015-03-01

Human noroviruses (NoVs) are the primary cause of acute gastroenteritis and are characterized by antigenic variation between genogroups and genotypes and antigenic drift of strains within the predominant GII.4 genotype. In the context of this diversity, an effective NoV vaccine must elicit broadly protective immunity. We used an antibody (Ab) binding blockade assay to measure the potential cross-strain protection provided by a multivalent NoV virus-like particle (VLP) candidate vaccine in human volunteers. Sera from ten human volunteers immunized with a multivalent NoV VLP vaccine (genotypes GI.1/GII.4) were analyzed for IgG and Ab blockade of VLP interaction with carbohydrate ligand, a potential correlate of protective immunity to NoV infection and illness. Immunization resulted in rapid rises in IgG and blockade Ab titers against both vaccine components and additional VLPs representing diverse strains and genotypes not represented in the vaccine. Importantly, vaccination induced blockade Ab to two novel GII.4 strains not in circulation at the time of vaccination or sample collection. GII.4 cross-reactive blockade Ab titers were more potent than responses against non-GII.4 VLPs, suggesting that previous exposure history to this dominant circulating genotype may impact the vaccine Ab response. Further, antigenic cartography indicated that vaccination preferentially activated preexisting Ab responses to epitopes associated with GII.4.1997. Study interpretations may be limited by the relevance of the surrogate neutralization assay and the number of immunized participants evaluated. Vaccination with a multivalent NoV VLP vaccine induces a broadly blocking Ab response to multiple epitopes within vaccine and non-vaccine NoV strains and to novel antigenic variants not yet circulating at the time of vaccination. These data reveal new information about complex NoV immune responses to both natural exposure and to vaccination, and support the potential feasibility of an efficacious multivalent NoV VLP vaccine for future use in human populations. ClinicalTrials.gov NCT01168401.

Broad Blockade Antibody Responses in Human Volunteers after Immunization with a Multivalent Norovirus VLP Candidate Vaccine: Immunological Analyses from a Phase I Clinical Trial

PubMed Central

Lindesmith, Lisa C.; Ferris, Martin T.; Mullan, Clancy W.; Ferreira, Jennifer; Debbink, Kari; Swanstrom, Jesica; Richardson, Charles; Goodwin, Robert R.; Baehner, Frank; Mendelman, Paul M.; Bargatze, Robert F.; Baric, Ralph S.

2015-01-01

Background Human noroviruses (NoVs) are the primary cause of acute gastroenteritis and are characterized by antigenic variation between genogroups and genotypes and antigenic drift of strains within the predominant GII.4 genotype. In the context of this diversity, an effective NoV vaccine must elicit broadly protective immunity. We used an antibody (Ab) binding blockade assay to measure the potential cross-strain protection provided by a multivalent NoV virus-like particle (VLP) candidate vaccine in human volunteers. Methods and Findings Sera from ten human volunteers immunized with a multivalent NoV VLP vaccine (genotypes GI.1/GII.4) were analyzed for IgG and Ab blockade of VLP interaction with carbohydrate ligand, a potential correlate of protective immunity to NoV infection and illness. Immunization resulted in rapid rises in IgG and blockade Ab titers against both vaccine components and additional VLPs representing diverse strains and genotypes not represented in the vaccine. Importantly, vaccination induced blockade Ab to two novel GII.4 strains not in circulation at the time of vaccination or sample collection. GII.4 cross-reactive blockade Ab titers were more potent than responses against non-GII.4 VLPs, suggesting that previous exposure history to this dominant circulating genotype may impact the vaccine Ab response. Further, antigenic cartography indicated that vaccination preferentially activated preexisting Ab responses to epitopes associated with GII.4.1997. Study interpretations may be limited by the relevance of the surrogate neutralization assay and the number of immunized participants evaluated. Conclusions Vaccination with a multivalent NoV VLP vaccine induces a broadly blocking Ab response to multiple epitopes within vaccine and non-vaccine NoV strains and to novel antigenic variants not yet circulating at the time of vaccination. These data reveal new information about complex NoV immune responses to both natural exposure and to vaccination, and support the potential feasibility of an efficacious multivalent NoV VLP vaccine for future use in human populations. Trial Registration ClinicalTrials.gov NCT01168401 PMID:25803642

Analysis of cross-resistance to Vip3 proteins in eight insect colonies, from four insect species, selected for resistance to Bacillus thuringiensis insecticidal proteins.

PubMed

Gomis-Cebolla, Joaquín; Wang, Yuequin; Quan, Yudong; He, Kanglai; Walsh, Tom; James, Bill; Downes, Sharon; Kain, Wendy; Wang, Ping; Leonard, Kathy; Morgan, Tom; Oppert, Brenda; Ferré, Juan

2018-05-16

Bacillus thuringiensis Vip3 proteins are synthesized and secreted during the vegetative growth phase. They are activated by gut proteases, recognize and bind to midgut receptors, form pores and lyse cells. We tested the susceptibility to Vip3Aa and Vip3Ca of Cry1A-, Cry2A-, Dipel- and Vip3-resistant insect colonies from different species to determine whether resistance to other insecticidal proteins confers cross-resistance to Vip3 proteins. As expected, the colonies resistant to Cry1A proteins, Dipel (Helicoverpa armigera, Trichoplusia ni, Ostrinia furnacalis and Plodia interpunctella) or Cry2Ab (H. armigera and T. ni) were not cross-resistant to Vip3 proteins. In contrast, H. armigera colonies resistant to Vip3Aa or Vip3Aa/Cry2Ab showed cross-resistance to the Vip3Ca protein. Moreover, the Vip3Ca protein was highly toxic to O. furnacalis (LC 50 not significantly different from that of Cry1Ab), whereas the Vip3Aa protein only showed moderate growth inhibition at the highest concentration tested (100 µg/g of diet). These results extend the cross-resistance studies between Vip3 and Cry proteins, show for the first time cross-resistance between proteins within the Vip3 subfamily, and points to O. furnacalis as a target for the Vip3Ca protein. Copyright © 2018 Elsevier Inc. All rights reserved.

FTO genotype is associated with exercise training-induced changes in body composition

PubMed Central

Rankinen, Tuomo; Rice, Treva; Teran-Garcia, Margarita; Rao, D.C.; Bouchard, Claude

2010-01-01

The fat mass and obesity associated (FTO) gene is the first obesity-susceptibility gene identified by genome-wide association scans and confirmed in several follow-up studies. Homozygotes for the risk allele (A/A) have 1.67 times greater risk of obesity than those who do not have the allele. However, it is not known if regular exercise-induced changes in body composition are influenced by the FTO genotype. The purpose of our study was to test if the FTO genotype is associated with exercise-induced changes in adiposity. Body composition was derived from underwater weighing before and after a 20-week endurance training program in 481 previously sedentary white subjects of the HERITAGE Family Study. FTO SNP rs8050136 was genotyped using Illumina GoldenGate assay. In the sedentary state, the A/A homozygotes were significantly heavier and fatter than the heterozygotes and the C/C homozygotes in men (p=0.004) but not in women (p=0.331; gene-by-sex interaction p=0.0053). The FTO genotype was associated with body fat responses to regular exercise (p<0.005; adjusted for age, sex, and baseline value of response trait): carriers of the C-allele showed three times greater fat mass and %body fat losses than the A/A homozygotes. The FTO genotype explained 2% of the variance in adiposity changes. Our data suggest that the FTO obesity-susceptibility genotype influences the body fat responses to regular exercise. Resistance to exercise-induced reduction in total adiposity may represent one mechanism by which the FTO A allele promotes overweight and obesity. PMID:19543202

Association of Taq I, Fok I and Apa I polymorphisms in Vitamin D Receptor (VDR) gene with leprosy.

PubMed

Neela, Venkata Sanjeev Kumar; Suryadevara, Naveen Chandra; Shinde, Vidya Gouri; Pydi, Satya Sudheer; Jain, Suman; Jonnalagada, Subbanna; Singh, Surya Satyanarayana; Valluri, Vijaya Lakshmi; Anandaraj, M P J S

2015-06-01

Vitamin D Receptor (VDR) is a transacting transcription factor which mediates immunomodulatory function and plays a key role in innate and adaptive immune responses through its ligand and polymorphisms in VDR gene may affect its regulatory function. To investigate the association of three VDR gene polymorphisms (TaqI rs731236, FokI rs2228570 and ApaI rs7975232) with leprosy. The study group includes 404 participants of which 222 were leprosy patients (paucibacillary=87, multibacillary=135) and 182 healthy controls. Genotyping was done using PCR-RFLP technique. Statistical analysis was performed using SNP Stats and PLINK software. The VDR FokI (rs2228570) ff genotype, ApaI (rs7975232) AA, Aa genotype and haplotype T-f-a, T-F-A were positively associated with leprosy when compared to healthy controls. The two variants at Fok and Apa positions in VDR gene are significantly associated with leprosy. Genotypes at FokI (ff), ApaI (aa) and haplotype (T-F-a, T-f-a) may contribute to the risk of developing leprosy by altering VDR phenotype/levels subsequently modulation of immune response. Copyright © 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Peer Smoking and the Nicotinic Receptor Genes: An Examination of Genetic and Environmental Risks for Nicotine Dependence

PubMed Central

Johnson, Eric O.; Chen, Li-Shiun; Breslau, Naomi; Hatsukami, Dorothy; Robbins, Tania; Saccone, Nancy L.; Grucza, Richard A.; Bierut, Laura J.

2010-01-01

Background Peer smoking provides a socially reinforcing context of friends’ encouragement and approval that contributes to smoking behavior. Twin studies show correlations and interactions between peer substance use and genetic liability for substance use. However, none examined specific genes. Here we test the hypothesis that the nicotinic receptor genes CHRNA5 (rs16969968), CHRNA3 (rs578776), CHRNB3 (rs13277254), and CHRND (rs12466358) modify the risk for nicotine dependence (ND) associated with peer smoking. Methods Cases of current nicotine dependence (FTND ≥ 4) and smoking-exposed (smoked 100+ cigarettes lifetime), but non-dependent controls (lifetime FTND = 0) came from the Collaborative Genetic Study of Nicotine Dependence (n=2,038). Peer smoking was retrospectively assessed for grades 9–12. Results Peer smoking and the four SNPs were associated with ND. A statistically significant interaction was found between peer smoking and rs16969968 (p = 0.0077). Overall risk of ND was highest for the rs16969968 AA genotype. However, variance in ND attributable to peer smoking was substantially lower among those with the AA genotype at rs16969968 than the lower risk genotypes: AA = 2.5%, GA/AG = 11.2%, GG = 14.2%; p ≤ 0.004. Conclusions Peer smoking had a substantially lower effect on ND among those with the high risk AA genotype at the functional SNP rs16969968 (CHRNA5) than among those with lower risk genotypes. Such results highlight the possibility that given drug exposure those with specific genetic risks may be less affected by social contexts and intervention strategies focused on social factors could have less influence on those at highest genetic risk. PMID:20840187

Polymorphism of regulatory region of GHRL gene (-2531C>T) as a promising predictive factor for radiotherapy-induced oral mucositis in patients with head neck cancer.

PubMed

Brzozowska, Anna; Homa-Mlak, Iwona; Mlak, Radosław; Gołębiowski, Paweł; Mazurek, Marcin; Ciesielka, Marzanna; Małecka-Massalska, Teresa

2018-03-22

The purpose of this study was to investigate the relationship between single nucleotide polymorphisms (SNP; rs1629816) in the regulatory region (c.-2531C>T) of the ghrelin (GHRL) gene and the occurrence and severity of oral mucositis caused by radiotherapy (RT) in patients with head and neck cancer. Oral mucositis in 65 patients with head and neck cancer who underwent irradiation were assessed according to Radiation Therapy Oncology Group (RTOG)/European Organisation for Research and Treatment of Cancer (EORTC) scale. The DNA from patients with head and neck cancer was isolated from whole blood. The genotypes were determined using the minisequencing method (SNaPshot PCR). The frequency of occurrence of the GHRL gene (c.-2531C>T, rs1629816) genotypes were as follows: AA = 21.5%; GA = 40%; and GG = 38.5%. In case of AA genotype, there was a 7-fold decrease of the risk of occurrence of oral mucositis (of grades 2 and 3) in the sixth week of RT (AA vs GA or GG, respectively: 17.9% vs 82.1% patients; odds ratio [OR] 0.14; 95% confidence interval [CI] 0.02-0.98; P = .0481). No statistically significant differences were observed between the volume of oral cavity contours (V30, V40, and V50) depending on the GHRL genotype in patients with head and neck cancer. The study results have demonstrated an association between the AA genotype of the GHRL gene and the risk of more severe oral mucositis attributed to RT in patients with head and neck cancer. © 2018 Wiley Periodicals, Inc.

Variation in PPP3CC Genotype Is Associated with Long-Term Recovery after Severe Brain Injury.

PubMed

Osier, Nicole D; Bales, James W; Pugh, Bunny; Shin, Samuel; Wyrobek, Julie; Puccio, Ava M; Okonkwo, David O; Ren, Dianxu; Alexander, Sheila; Conley, Yvette P; Dixon, C Edward

2017-01-01

After experimental traumatic brain injury (TBI), calcineurin is upregulated; blocking calcineurin is associated with improved outcomes. In humans, variation in the calcineurin A-gamma gene (PPP3CC) has been associated with neuropsychiatric disorders, though any role in TBI recovery remains unknown. This study examines associations between PPP3CC genotype and mortality, as well as gross functional status assessed at admission using the Glasgow Coma Scale (GCS) and at 3, 6, and 12 months after severe TBI using the Glasgow Outcome Score (GOS). The following tagging single nucleotide polymorphisms (tSNPs) in PPP3CC were genotyped: rs2443504, rs2461491, rs2469749, and rs10108011. The rs2443504 AA genotype was univariately associated with GCS (p = 0.022), GOS at 3, 6, and 12 months (p = 0.002, p = 0.034, and p = 0.004, respectively), and mortality (p = 0.007). In multivariate analysis controlling for age, sex, and GCS, the AA genotype of rs2443504 was associated with GOS at 3 (p = 0.02), and 12 months (p = 0.01), with a trend toward significance at 6 months (p = 0.05); the AA genotype also was associated with mortality in the multivariate model (p = 0.04). Further work is warranted to better understand the role of calcineurin, as well as the genes encoding it and their relevance to outcomes after brain injury.

Pharmacogenetic association between GSTP1 genetic polymorphism and febrile neutropenia in Japanese patients with early breast cancer.

PubMed

Sugishita, Mihoko; Imai, Tsuneo; Kikumori, Toyone; Mitsuma, Ayako; Shimokata, Tomoya; Shibata, Takashi; Morita, Sachi; Inada-Inoue, Megumi; Sawaki, Masataka; Hasegawa, Yoshinori; Ando, Yuichi

2016-03-01

Genetic risk factors for febrile neutropenia (FN), the major adverse event of perioperative chemotherapy for early breast cancer, remain unclear. This study retrospectively explored pharmacogenetic associations of single nucleotide polymorphisms (SNPs) of the uridine glucuronosyltransferase 2B7 (UGT2B7, rs7668258), glutathione-S-transferase pi 1 (GSTP1, rs1695), and microcephalin 1 (MCPH1, rs2916733) genes with chemotherapy-related adverse events in 102 Japanese women who received epirubicin and cyclophosphamide as perioperative chemotherapy for early breast cancer. The allele frequencies for all of the SNPs were in concordance with the Hap-Map data of Japanese individuals. Among the 24 patients who had FN at least once during all courses of chemotherapy, 23 had the A/A genotype, and 1 had the A/G genotype of the GSTP1 polymorphism (rs1695, P = 0.001); 23 of the 70 patients with the A/A genotype had FN, as compared with only 1 of the 32 patients with the A/G and G/G genotypes. The genotype distributions of the UGT2B7 and MCPH1 polymorphisms did not differ between the patients who had FN or grade 3/4 neutropenia and those who did not. Among Japanese women who received epirubicin and cyclophosphamide as perioperative chemotherapy for early breast cancer, those with the A/A genotype of the GSTP1 polymorphism (rs1695) were more likely to have FN.

[Polymorphisms of bGH, RORC, and DGAT1 genes in Russian beef cattle breeds].

PubMed

Gorlov, I F; Fedunin, A A; Randelin, D A; Sulimova, G E

2014-12-01

We examined the allelic and genotypic polymorphisms of genes of the retinoic acid receptor-related orphan receptor C (RORC), diacylglycerol acyltransferase-1 (DGAT1), and growth hormone (bGH) in Russian beef cattle breeds in two populations of Kazakh white-headed cattle (of Kazakh and Russian selection) and in the Kalmyk cattle breed and Mongolian hogorogo breed, which is related to Kalmyk breed. The studied genes are associated with parameters of meat quality: marbleness (bGH and RORC) and tenderness (DGAT1). They are also associated with an increase in carcass weight (bGH). We found that Russian and Kazakh populations of the Kazakh white-headed.breed were characterized by a high content of the AA genotype of RORC (0.713 and 0.608, respectively) and of the AA genotype of DGAT1 (0.913 and 0.975), both of which are preferable for meat quality. The total frequencies for the combined genotypes for the bGH and RORC genes, which provide for superior meat quality and carcass weight, in the populations of Kazakh white-headed cattle (GG/AA and GC/AA-68.8% and 57% in the Russian and Kazakh populations, respectively) exceeded the frequencies in the two other studied breeds by two times. Overall, the obtained results point to the high genetic potential of both populations of Kazakh white-headed cattle breeds in beef production. Results of this study can be used to improve the selection of meat traits in industrial livestock.

Serotonin 2A Receptor SNP rs7330461 Association with Treatment Response to Pomaglumetad Methionil in Patients with Schizophrenia

PubMed Central

Nisenbaum, Laura K.; Downing, AnnCatherine M.; Zhao, Fangyi; Millen, Brian A.; Munsie, Leanne; Kinon, Bruce J.; Adams, David H.; Gomez, Juan Carlos; Penny, Michelle Ann

2016-01-01

This study aims to confirm the initial pharmacogenetic finding observed within the clinical proof-of-concept trial of an enhanced response to treatment with pomaglumetad methionil (LY2140023 monohydrate) in Caucasian schizophrenia patients homozygous for T/T at single nucleotide polymorphism rs7330461 in the serotonin (5-hydroxytryptamine) 2A receptor gene compared to A/A homozygous patients. The effect of the rs7330461 genotype on the response to pomaglumetad methionil treatment was assessed in three additional clinical trials and in an integrated analysis. Overall, this study includes data from 1115 Caucasian patients for whom genotyping information for rs7330461 was available, consisting of 513 A/A homozygous, 466 A/T heterozygous and 136 T/T homozygous patients. Caucasian T/T homozygous patients showed significantly (p ≤ 0.05) greater improvement in Positive and Negative Syndrome Scale (PANSS) total scores during treatment with pomaglumetad methionil 40 mg twice daily compared to A/A homozygous patients. Additionally, T/T homozygous patients receiving pomaglumetad methionil had significantly (p ≤ 0.05) greater improvements in PANSS total scores compared to placebo and similar improvements as T/T homozygous patients receiving standard-of-care (SOC) treatment. The findings reported here in conjunction with prior reports show that in Caucasian patients with schizophrenia, the T/T genotype at rs7330461 is consistently associated with an increased treatment response to pomaglumetad methionil compared to the A/A genotype. PMID:26861400

Serotonin 2A Receptor SNP rs7330461 Association with Treatment Response to Pomaglumetad Methionil in Patients with Schizophrenia.

PubMed

Nisenbaum, Laura K; Downing, AnnCatherine M; Zhao, Fangyi; Millen, Brian A; Munsie, Leanne; Kinon, Bruce J; Adams, David H; Gomez, Juan Carlos; Penny, Michelle Ann

2016-02-05

This study aims to confirm the initial pharmacogenetic finding observed within the clinical proof-of-concept trial of an enhanced response to treatment with pomaglumetad methionil (LY2140023 monohydrate) in Caucasian schizophrenia patients homozygous for T/T at single nucleotide polymorphism rs7330461 in the serotonin (5-hydroxytryptamine) 2A receptor gene compared to A/A homozygous patients. The effect of the rs7330461 genotype on the response to pomaglumetad methionil treatment was assessed in three additional clinical trials and in an integrated analysis. Overall, this study includes data from 1115 Caucasian patients for whom genotyping information for rs7330461 was available, consisting of 513 A/A homozygous, 466 A/T heterozygous and 136 T/T homozygous patients. Caucasian T/T homozygous patients showed significantly (p ≤ 0.05) greater improvement in Positive and Negative Syndrome Scale (PANSS) total scores during treatment with pomaglumetad methionil 40 mg twice daily compared to A/A homozygous patients. Additionally, T/T homozygous patients receiving pomaglumetad methionil had significantly (p ≤ 0.05) greater improvements in PANSS total scores compared to placebo and similar improvements as T/T homozygous patients receiving standard-of-care (SOC) treatment. The findings reported here in conjunction with prior reports show that in Caucasian patients with schizophrenia, the T/T genotype at rs7330461 is consistently associated with an increased treatment response to pomaglumetad methionil compared to the A/A genotype.

Longitudinal data analysis of polymorphisms in the κ-casein and β-lactoglobulin genes shows differential effects along the trajectory of the lactation curve in tropical dairy goats.

PubMed

Cardona, Samir Julián Calvo; Cadavid, Henry Cardona; Corrales, Juan David; Munilla, Sebastián; Cantet, Rodolfo J C; Rogberg-Muñoz, Andrés

2016-09-01

The κ-casein (CSN-3) and β-lactoglobulin (BLG) genes are extensively polymorphic in ruminants. Several association studies have estimated the effects of polymorphisms in these genes on milk yield, milk composition, and cheese-manufacturing properties. Usually, these results are based on production integrated over the lactation curve or on cross-sectional studies at specific days in milk (DIM). However, as differential expression of milk protein genes occurs over lactation, the effect of the polymorphisms may change over time. In this study, we fitted a mixed-effects regression model to test-day records of milk yield and milk quality traits (fat, protein, and total solids yields) from Colombian tropical dairy goats. We used the well-characterized A/B polymorphisms in the CSN-3 and BLG genes. We argued that this approach provided more efficient estimators than cross-sectional designs, given the same number and pattern of observations, and allowed exclusion of between-subject variation from model error. The BLG genotype AA showed a greater performance than the BB genotype for all traits along the whole lactation curve, whereas the heterozygote showed an intermediate performance. We observed no such constant pattern for the CSN-3 gene between the AA homozygote and the heterozygote (the BB genotype was absent from the sample). The differences among the genotypic effects of the BLG and the CSN-3 polymorphisms were statistically significant during peak and mid lactation (around 40-160 DIM) for the BLG gene and only for mid lactation (80-145 DIM) for the CSN-3 gene. We also estimated the additive and dominant effects of the BLG locus. The locus showed a statistically significant additive behavior along the whole lactation trajectory for all quality traits, whereas for milk yield the effect was not significant at later stages. In turn, we detected a statistically significant dominance effect only for fat yield in the early and peak stages of lactation (at about 1-45 DIM). The longitudinal analysis of test-day records allowed us to estimate the differential effects of polymorphisms along the lactation curve, pointing toward stages that could be affected by the gene. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Band gap modulation of mono and bi-layer hexagonal ZnS under transverse electric field and bi-axial strain: A first principles study

NASA Astrophysics Data System (ADS)

Rai, D. P.; Kaur, Sumandeep; Srivastava, Sunita

2018-02-01

Density functional theory has been employed to study the electronic and mechanical properties of the monolayer and bilayer ZnS. AB stacked ZnS bilayer is found to be energetically more favorable over the AA stacked ZnS bilayer. The electronic bandgap decreases on moving from monolayer to bilayer. Application of positive transverse electric field in AA/AB stacked bilayers leads to a semiconductor to metal transition at 1.10 V/Å. Reversed polarity of electric field, on the other hand, leads to an asymmetric behavior of the bandgap for AB stacking while the behavior of the bandgap in AA stacking is polarity independent. The strong dependency of bandgap on polarity of electric field in AB stacked ZnS bilayer is due to the balancing of external field with the induced internal field which arises due the electronegativity and heterogeneity in the arrangements of atoms. The electronic structure varies with the variation of applied biaxial strain (compression/tensile). We report an increase in band gap in both single and double layers under compression up to -8.0%, which can be attributed to greater superposition of atomic orbitals (Zn-d and S-p hybridization). We expect that our results may stimulate more theoretical and experimental work on hexagonal multi-layers of ZnS employing external field (temperature, pressure, field etc.) for future applications of our present work.

2. Basement tunnel plan: Pine (Building 6, HABS DC349AA), Linden ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

2. Basement tunnel plan: Pine (Building 6, HABS DC-349-AA), Linden (Building 28 HABS DC-349-AD), Holly (Building 29, HABS DC-349-AE), East Lodge / Detached Nurses Home (Building 30, HABS DC-349-AB) - St. Elizabeths Hospital, Tunnels, 2700 Martin Luther King Jr. Avenue, Southeast, Washington, District of Columbia, DC

Polymorphisms of MRF4 and H-FABP genes association with growth traits in Qinchuan cattle and related hybrids.

PubMed

Wang, Shan; Cai, Xin; Xue, Kai; Chen, Hong

2011-02-01

PCR-RFLP was applied to analyse polymorphisms within the MRF4 and heart fatty acid-binding protein (H-FABP) gene for correlation studies with growth traits in three-month-old Qinchuan (QQ), Qinchuan × Limousin (LQ) and Qinchuan × Red Angus (AQ) cattle. The results showed that 874 bp PCR products of MRF4 digested with XbaI and 2,075 bp PCR products of H-FABP digested with HaeIII were polymorphic in the three populations. Moreover, the frequencies of allele A at MRF4 locus and allele B at H-FABP locus in the QQ, AQ, and LQ populations were 0.8358/0.8888/0.8273 and 0.8358/0.7500/0.8195 respectively. Allele A at MRF4 locus and allele B at H-FABP locus were dominant in the three populations. No statistically significant differences in growth traits were observed among the genotypes of the all three populations at H-FABP locus. However, the association of MRF4 polymorphism with growth traits was then determined in all three populations. The body weight, withers height, heart girth and height at hip cross of individuals with genotype AA were higher than those with genotype AB or BB (P < 0.05). Therefore, we suggest that the MRF4 gene may function in the control or expression of growth traits, particularly body weight, withers height, heart girth and height at hip cross.

[The association of polymorphisms in SLC18A1, TPH1 and RELN genes with risk of paranoid schizophrenia].

PubMed

Galaktionova, D Iu; Gareeva, A E; Khusnutdinova, E K; Nasedkina, T V

2014-01-01

We have developed a biochip for the analysis of polymorphisms in candidate genes for schizophrenia: DISC1, RELN, ZNF804A, PLXNA2, COMT, SLC18A41, CACNA1C, ANK3, TPH1, PLAA and SNAP-25. Using biochip the allele and genotype frequencies in 198 patients with schizophrenia and 192 healthy individuals have been obtained. For SLC18A1 polymorphism rs2270641 A>C, the frequencies of A allele (p = 0.007) and AA genotype (p = 0.002) were lower in patients compared with healthy individuals. A significant association was found between AA genotype (p = 0.036) of the TPH1 polymorphism rs1800532 C>A and schizophrenia. The C allele (p = 0.039) of the RELNpolymorphism rs7341475 C>T were lower in patients with schizophrenia compared with healthy individuals in a tatar population. Genotype AA of the TPH1 polymorphism rs1800532 C>A were more frequent in patients with schizophrenia compared with healthy individuals. Ithas been shown that the C allele (p = 0.0001) and GC (p = = 0.0001) genotype of the PLXNA2 polymorphism rs1327175 G>C are associated with the family history in patients with paranoid schizophrenia. The obtained data suggest that SLC18A1, TPH1 and RELN gene polymorphisms are associated with the risk of paranoid schizophrenia.

A functional NPSR1 gene variant and environment shape personality and impulsive action: a longitudinal study.

PubMed

Laas, Kariina; Reif, Andreas; Kiive, Evelyn; Domschke, Katharina; Lesch, Klaus-Peter; Veidebaum, Toomas; Harro, Jaanus

2014-03-01

Neuropeptide S and its receptor NPSR1 are involved in the regulation of arousal, attention and anxiety. We examined whether the NPSR1 gene functional polymorphism Asn¹⁰⁷Ile (rs324981, A>T) influences personality, impulsivity, and attention-deficit/hyperactivity disorder (ADHD)-related symptoms in a population-representative sample, and whether any eventual associations depend on age, sex, family relations and stressful life events (SLE). We used self-reports or teachers' ratings for both the younger (n=593) and older (n=583) cohort of the longitudinal Estonian Children Personality, Behaviour and Health Study. Males with the TT genotype displayed more ADHD-related symptoms. Adaptive impulsivity and Extraversion increased the most from age 18 to 25. While highest increases were observed in AA men, TT women exhibited the largest decreases. For participants with the AA genotype, Warmth in family was inversely associated with Neuroticism, and positively associated with Extraversion and Adaptive impulsivity. High exposure to SLE increased impulsivity and ADHD scores in TT genotype subjects. We conclude that the NPSR1 A/T polymorphism is associated with impulsivity, ADHD symptoms and personality, mirroring the activity- and anxiety-mediating role of NPSR1. Heterozygous individuals were the least sensitive to environmental factors, whereas subjects with the AA genotype and TT genotype reacted to different types of environmental adversities.

The Gene-Lifestyle Interaction on Leptin Sensitivity and Lipid Metabolism in Adults: A Population Based Study.

PubMed

Luglio, Harry Freitag; Sulistyoningrum, Dian Caturini; Huriyati, Emy; Lee, Yi Yi; Wan Muda, Wan Abdul Manan

2017-07-07

Obesity has been associated with leptin resistance and this might be caused by genetic factors. The aim of this study was to investigate the gene-lifestyle interaction between -866G/A UCP2 (uncoupling protein 2) gene polymorphism, dietary intake and leptin in a population based study. This is a cross sectional study conducted in adults living at urban area of Yogyakarta, Indonesia. Data of adiposity, lifestyle, triglyceride, high density lipoprotein (HDL) cholesterol, leptin and UCP2 gene polymorphism were obtained in 380 men and female adults. UCP2 gene polymorphism was not significantly associated with adiposity, leptin, triglyceride, HDL cholesterol, dietary intake and physical activity (all p > 0.05). Leptin was lower in overweight subjects with AA + GA genotypes than those with GG genotype counterparts ( p = 0.029). In subjects with AA + GA genotypes there was a negative correlation between leptin concentration ( r = -0.324; p < 0.0001) and total energy intake and this correlation was not seen in GG genotype ( r = -0.111; p = 0.188). In summary, we showed how genetic variation in -866G/A UCP2 affected individual response to leptin production. AA + GA genotype had a better leptin sensitivity shown by its response in dietary intake and body mass index (BMI) and this explained the protective effect of A allele to obesity.

Mannose-binding lectin codon 54 gene polymorphism in relation to risk of nosocomial invasive fungal infection in preterm neonates in the neonatal intensive care unit.

PubMed

Aydemir, Cumhur; Onay, Huseyin; Oguz, Serife Suna; Ozdemir, Taha Resid; Erdeve, Omer; Ozkinay, Ferda; Dilmen, Ugur

2011-09-01

Preterm neonates are susceptible to infection due to a combination of sub-optimal immunity and increased exposure to invasive organisms. Invasive fungal infections are associated with significant morbidity and mortality among preterm infants cared for in the neonatal intensive care unit (NICU). Mannose-binding lectin (MBL) is a component of the innate immune system, which may be especially important in the neonatal setting. The objective of this study was to investigate the presence of any association between MBL gene polymorphism and nosocomial invasive fungal infection in preterm neonates. Codon 54 (B allele) polymorphism in exon 1 of the MBL gene was investigated in 31 patients diagnosed as nosocomial invasive fungal infection and 30 control preterm neonates. AB genotype was determined in 26% and 30% of patient and control groups, respectively, and the difference was not statistically significant. AA genotype was determined in 74% of the patient group and in 67% of the control group, and the difference was not statistically significant. B allele frequency was not different significantly in the patient group (13%) compared to the control group (18%). In our study, no relationship was found between MBL codon 54 gene polymorphism and the risk of nosocomial invasive fungal infection in preterm neonates in NICU.

Association between angiotensin II type 1 receptor polymorphism and sudden cardiac death in myocardial infarction.

PubMed

Kruzliak, Peter; Kovacova, Gabriela; Pechanova, Olga; Balogh, Stefan

2013-01-01

The renin-angiotensin system is involved in the pathogenesis of coronary artery disease and myocardial infarction (MI). Angiotensin II (Ang II) has many adverse effects such as vasoconstriction and vascular remodeling, and these actions are mediated by the angiotensin II type 1 receptor (AT1R). A total of 1376 patients were recruited from January 2010 to April 2012. The study group consisted of 749 patients with ACS (317 females and 432 males) and of 627 healthy controls. The ACS patients demonstrated a lower proportion of AA genotypes and AC genotypes but higher proportions of CC genotypes than the control population. The AT1R CC genotype conferred a 2.76-fold higher risk of MI compared with the genotype AC and AA. In addition, the CC genotype was also associated with a 4.08 times higher risk of left anterior descending artery infarction and a 3.07 times higher risk of anterior wall infarction. We also found that the CC genotype was independently associated with sudden cardiac death. This study demonstrated that the AT1R CC genotype is an independent risk factor for ACS incidence, and this genotype is associated with a greater ACS severity and greater risk of sudden cardiac death.

Effects of NOS1AP rs12742393 polymorphism on repaglinide response in Chinese patients with type 2 diabetes mellitus.

PubMed

Wang, Tao; Wang, Yan; Lv, Dong-Mei; Song, Jin-Fang; Lu, Qian; Gao, Xing; Zhang, Fan; Guo, Hao; Li, Wei; Yin, Xiao-Xing

2014-02-01

To investigate the associations of NOS1AP rs12742393 polymorphism with the risk of type 2 diabetes mellitus (T2DM) and repaglinide therapeutic efficacy in Chinese patients with T2DM. Prospective case-control study. Academic medical center. A total of 300 patients with T2DM and 200 healthy volunteers were enrolled to identify NOS1AP rs12742393 genotypes using the polymerase chain reaction-restriction fragment length polymorphism assay. Eighty-four patients with various genotypes were randomly selected to receive oral repaglinide as a single-agent therapy (3 mg/day) for 8 weeks. Anthropometric measurements and fasting plasma glucose (FPG), postprandial plasma glucose, hemoglobin A1c , fasting serum insulin (FINS), postprandial serum insulin, homeostasis model assessment for insulin resistance (HOMA-IR), triglyceride, total cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol tests were obtained before and after repaglinide treatment. The risk C allelic frequency of NOS1AP rs12742393 was higher in patients with T2DM than in healthy volunteers (p<0.001). Patients with T2DM and genotypes AA and AC at NOS1AP rs12742393 had a significant reduction in FPG (mmol/l) compared with those with genotype CC (p<0.01). Patients with CC homozygotes and AC heterozygotes had a greater increase in FINS (mU/l) than those with wild-type AA (p<0.05). In addition, the carriers of genotype CC at NOS1AP rs12742393 had higher differential values of HOMA-IR compared with genotypes AC and AA carriers (p<0.001). The effects of repaglinide treatment on FPG (p<0.01), FINS (p<0.05) and HOMA-IR (p<0.001) were reduced in patients with T2DM carrying the NOS1AP rs12742393 risk C allele compared with the AA genotype carriers. The NOS1AP rs12742393 polymorphism is associated with therapeutic efficacy of repaglinide in Chinese T2DM patients. © 2013 Pharmacotherapy Publications, Inc.

GABBR1 and SLC6A1, Two Genes Involved in Modulation of GABA Synaptic Transmission, Influence Risk for Alcoholism: Results from Three Ethnically Diverse Populations.

PubMed

Enoch, Mary-Anne; Hodgkinson, Colin A; Shen, Pei-Hong; Gorodetsky, Elena; Marietta, Cheryl A; Roy, Alec; Goldman, David

2016-01-01

Animal and human studies indicate that GABBR1, encoding the GABAB1 receptor subunit, and SLC6A1, encoding the neuronal gamma-aminobutyric acid (GABA) transporter GAT1, play a role in addiction by modulating synaptic GABA. Therefore, variants in these genes might predict risk/resilience for alcoholism. This study included 3 populations that differed by ethnicity and alcoholism phenotype: African American (AA) men: 401 treatment-seeking inpatients with single/comorbid diagnoses of alcohol and drug dependence, 193 controls; Finnish Caucasian men: 159 incarcerated alcoholics, half with comorbid antisocial personality disorder, 181 controls; and a community sample of Plains Indian (PI) men and women: 239 alcoholics, 178 controls. Seven GABBR1 tag single nucleotide polymorphisms were genotyped in the AA and Finnish samples; rs29220 was genotyped in the PI for replication. Also, a uniquely African, functional SLC6A1 insertion promoter polymorphism (IND) was genotyped in the AAs. We found a significant and congruent association between GABBR1 rs29220 and alcoholism in all 3 populations. The major genotype (heterozygotes in AAs, Finns) and the major allele in PIs were significantly more common in alcoholics. Moreover, SLC6A1 IND was more abundant in controls, that is, the major genotype predicted alcoholism. An analysis of combined GABBR1 rs29220 and SLC6A1 IND genotypes showed that rs29220 heterozygotes, irrespective of their IND status, had an increased risk for alcoholism, whereas carriers of the IND allele and either rs29220 homozygote were more resilient. Our results show that with both GABBR1 and SLC6A1, the minor genotypes/alleles were protective against risk for alcoholism. Finally, GABBR1 rs29220 might predict treatment response/adverse effects for baclofen, a GABAB receptor agonist. Copyright © 2016 by the Research Society on Alcoholism. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Association of the AA genotype of the BCL2 (-938C>A) promoter polymorphism with better survival in ovarian cancer.

PubMed

Heubner, Martin; Wimberger, Pauline; Otterbach, Friedrich; Kasimir-Bauer, Sabine; Siffert, Winfried; Kimmig, Rainer; Nückel, Holger

2009-01-01

Bcl-2 plays a key role in the regulation of apoptosis. Recently, a novel regulatory single nucleotide polymorphism (-938C>A) in the inhibitory P2 BCL2 promoter was described. In this study we investigated its potential association with survival in epithelial ovarian cancer. Patients (n=110) with primary epithelial ovarian cancer were retrospectively genotyped by pyrosequencing. Genotype distribution was not significantly different between 110 ovarian cancer patients and 120 healthy controls, suggesting that genotypes of this polymorphism do not increase the susceptibility to ovarian cancer. Kaplan-Meier curves showed a significant association of the AA genotype with increased survival (p=0.002). Multivariate analysis revealed that the BCL2-938AC/CC genotype (hazard ratio 4.5; p=0.003) was an independent prognostic factor compared to other prognostic factors such as age, histological grade or tumor stage. The results suggest a role for the BCL2-938C>A polymorphism as a marker for survival in patients with epithelial ovarian cancer.

Role of IL-10 -1082, IFN-gamma +874, and TNF-alpha -308 genes polymorphisms in suicidal behavior.

PubMed

Omrani, Mir Davood; Bushehri, Behzad; Bagheri, Morteza; Salari-Lak, Shaker; Alipour, Azize; Anoshae, Mohamad-Reza; Massomi, Reza

2009-01-01

In this study, it was determined whether the IL-10 -1082, IFN-gamma +874, and TNF-alpha -308 polymorphisms were associated with suicidal behavior. One hundred forty five patients with suicidal behavior and 160 normal individuals were genotyped for IL-10 -1082, IFN-gamma +874, and TNF-alpha -308 polymorphisms using ASO-PCR method. TNF-alpha -308 G/G genotype has been increased in males with completed suicide behavior versus control group (p value = 0.017). IL-10 -1082 A/A genotype is higher in both male and female suicide completed groups (p value = 0.017). IFN-gamma (+874) A/A genotype was significantly higher in males with completed suicide behavior versus normal male control (p value = 0.027). It can be concluded that IL-10, IFN-gamma, and TNF-alpha polymorphisms may play a role in suicidal behavior.

Isolation and characterization of a new enterovirus F in yak feces in the Qinghai-Tibetan Plateau.

PubMed

He, Huan; Tang, Cheng; Chen, Xinnuo; Yue, Hua; Ren, Yupeng; Liu, Yan; Zhang, Bin

2017-02-01

An enterovirus (EV) strain, designated as SWUN-AB001, was isolated in the Qinghai-Tibetan Plateau from a yak with severe diarrheal disease. The complete genome of strain SWUN-AB001 was 7,382 bp in length and shared 35.1-68.5% nt identities with bovine EVs belonging to a candidate new type EV-F7. Using the sequence difference values in the VP1 gene as a criterion for demarcating a new serotype/genotype in the Enterovirus genus, strain SWUN-AB001 had only a 71.1% nt and a 79.2% aa identity, in the VP1 region, with the most closely matched EV, further indicating that a new type of EV had been identified. Phylogenetic analysis of the nt sequence of the viral polyprotein and of VP1 genes demonstrated that the virus fell within the EV-F cluster, but was located in a unique lineage. Furthermore, a large-scale surveillance study indicated that the prevalence of this EV in yaks was 31.05% (95% CI = 25.5-37.6%) in 235 animals with diarrhea and 24.13% (95% CI = 17.4-32.4%) in 116 healthy yaks. However, there was no significant difference in virus prevalence between diarrheal and healthy samples. Interestingly, in the Tibet region, diarrheal feces had a higher incidence of EVs than feces of healthy yaks (odd ratios = 6.03, 95% CI = 1.93-18.86), indicating that the incidence of EV was potentially correlated with the clinical symptom of diarrhea in yaks.

Human papillomavirus detection using the Abbott RealTime high-risk HPV tests compared with conventional nested PCR coupled to high-throughput sequencing of amplification products in cervical smear specimens from a Gabonese female population.

PubMed

Moussavou-Boundzanga, Pamela; Koumakpayi, Ismaël Hervé; Labouba, Ingrid; Leroy, Eric M; Belembaogo, Ernest; Berthet, Nicolas

2017-12-21

Cervical cancer is the fourth most common malignancy in women worldwide. However, screening with human papillomavirus (HPV) molecular tests holds promise for reducing cervical cancer incidence and mortality in low- and middle-income countries. The performance of the Abbott RealTime High-Risk HPV test (AbRT) was evaluated in 83 cervical smear specimens and compared with a conventional nested PCR coupled to high-throughput sequencing (HTS) to identify the amplicons. The AbRT assay detected at least one HPV genotype in 44.57% of women regardless of the grade of cervical abnormalities. Except for one case, good concordance was observed for the genotypes detected with the AbRT assay in the high-risk HPV category determined with HTS of the amplicon generated by conventional nested PCR. The AbRT test is an easy and reliable molecular tool and was as sensitive as conventional nested PCR in cervical smear specimens for detection HPVs associated with high-grade lesions. Moreover, sequencing amplicons using an HTS approach effectively identified the genotype of the hrHPV identified with the AbRT test.

A Replication and Extension of the Antisymmetry Effect in Pigeons

ERIC Educational Resources Information Center

Urcuioli, Peter J.; Swisher, Melissa

2012-01-01

Pigeons trained on successive AB symbolic matching show emergent BA antisymmetry if they are also trained on successive AA oddity and BB identity (Urcuioli, 2008, Experiment 4). In other words, when tested on BA probe trials following training, they respond more to the comparisons on the reverse of the nonreinforced AB baseline trials than on the…

Toxin Gene Contents and Activity of Bacillus thuringiensis Strains Against Two Sugarcane Borer Species, Diatraea saccharalis (F.) and D. flavipennella (Box).

PubMed

Silva, L M; Silva, M C; Silva, S M F A; Alves, R C; Siqueira, H A A; Marques, E J

2018-04-01

Bacillus thuringiensis (Berliner) bears essential characteristics in the control of insect pests, such as its unique mode of action, which confers specificity and selectivity. This study assessed cry gene contents from Bt strains and their entomotoxicity against Diatraea saccharalis (F.) and Diatraea flavipennella (Box) (Lepidoptera: Crambidae). Bioassays with Bt strains were performed against neonates to evaluate their lethal and sublethal activities and were further analyzed by PCR, using primers to identify toxin genes. For D. saccharalis and D. flavipennella, 16 and 18 strains showed over 30% larval mortality in the 7th day, respectively. The LC 50 values of strains for D. saccharalis varied from 0.08 × 10 5 (LIIT-0105) to 4104 × 10 5 (LIIT-2707) spores + crystals mL -1 . For D. flavipennella, the LC 50 values of strains varied from 0.40 × 10 5 (LIIT-2707) to 542 × 10 5 (LIIT-2109) spores + crystals mL -1 . For the LIIT-0105 strain, which was the most toxic to D. saccharalis, the genes cry1Aa, cry1Ab, cry1Ac, cry1B, cry1C, cry1D, cry1F, cry1I, cry2Aa, cry2Ab, cry8, and cry9C were detected, whereas for the strain LIIT-2707, which was the most toxic to D. flavipennella, detected genes were cry1Aa, cry1Ab, cry1Ac, cry1B, cry1D, cry1F, cry1I, cry2Aa, cry2Ab, and cry9. The toxicity data and toxin gene content in these strains of Bt suggest a great variability of activity with potential to be used in the development of novel biopesticides or as source of resistance genes that can be expressed in plants to control pests.

Variant in OXTR gene and functional connectivity of the hypothalamus in normal subjects.

PubMed

Wang, Junping; Qin, Wen; Liu, Bing; Wang, Dawei; Zhang, Yunting; Jiang, Tianzi; Yu, Chunshui

2013-11-01

The oxytocin receptor gene (OXTR) rs53576A has been associated with autism spectrum disorders (ASDs). A smaller hypothalamic volume has been reported in healthy male A-allele carriers than in male GG homozygotes and in patients with ASDs than in healthy controls. These findings prompt the hypothesis that male AA homozygotes may have weaker hypothalamic functional connectivity when compared to male G-allele carriers. We calculated local functional connectivity density (FCD) using a voxel-wise data-driven approach based on resting-state functional MRI data in 270 young healthy subjects. Both the main effect of genotype and the gender-by-genotype interaction were considered. Of the whole brain, only the local FCD of the hypothalamus exhibited the main effect of genotype. Post-hoc testing revealed significantly lower local FCD in male AA homozygotes compared to male G-allele carriers although there was only a trend of significance in the gender-by-genotype interaction. We further analyzed the resting-state functional connectivity (rsFC) of the hypothalamic region that demonstrating significant genotype differences in local FCD. We found a significant gender-by-genotype interaction in rsFC between the hypothalamic region and the left dorsolateral prefrontal cortex, but no significant main effect of genotype was found. Post-hoc testing revealed that this rsFC was significantly weaker in male AA homozygotes compared to male G-allele carriers. Our findings identify gender-dependent mechanisms of OXTR rs53576 gene variation impacting the functional connectivity of the hypothalamus in healthy individuals and suggest that these mechanisms are important for understanding ASDs. Copyright © 2013 Elsevier Inc. All rights reserved.

The correlation between TNF-α-308 gene polymorphism and susceptibility to cervical cancer.

PubMed

Li, Liping; Liu, Jie; Liu, Chunjing; Lu, Xianghui

2018-05-01

Tumor necrosis factor-α (TNF-α) is closely related to the occurrence of human cancers. Cervical cancer seriously affects female health. Therefore, our study aimed to investigate the correlation between the polymorphism of TNF-α-308 gene and susceptibility to cervical cancer. Whole blood was collected from 142 patients with cervical cancer and 150 healthy controls. PCR-RFLP was used to detect the polymorphism of TNF-α-308 and the correlation between polymorphism of TNF-α-308 and the susceptibility to cervical cancer was analyzed. The three genotypes of TNF-α-308 were GG, GA and AA, and the distributions of genotypes of TNF-α-308 were consistent with Hardy-Weinberg equilibrium in both cervical cancer group and control group. There were no significant differences in genotype and allele frequency between cervical cancer group and healthy control group (P>0.05). A/A genotype increased the risk of cervical cancer by 1.46 times with 95% confidence interval of 0.32-6.67. Different genotypes were not associated with tumor type (P>0.05). Different genotypes are correlated with cervical cancer TNM stages, tumor differentiation and lymph node metastasis. Proportion of GA+AA genotype in TNM stage III+IV group, low differentiation group and lymph node metastasis group were 28.1, 29.0 and 29.8%, respectively, which were significantly higher than those in stage I+II group, moderate/high differentiation group and non-lymph node metastasis group (P<0.05). The results suggested that TNF-α-308 gene polymorphism is associated with the degree of malignancy of cervical cancer. Female patients with A allele have higher malignant degree of cervical cancer.

The AA genotype of the regulatory BCL2 promoter polymorphism ( 938C>A) is associated with a favorable outcome in lymph node negative invasive breast cancer patients.

PubMed

Bachmann, Hagen S; Otterbach, Friedrich; Callies, Rainer; Nückel, Holger; Bau, Maja; Schmid, Kurt W; Siffert, Winfried; Kimmig, Rainer

2007-10-01

Expression of the antiapoptotic and antiproliferative protein Bcl-2 has been repeatedly shown to be associated with better clinical outcome in breast cancer. We recently showed a novel regulatory (-938C>A) single-nucleotide polymorphism (SNP) in the inhibitory P2 BCL2 gene promoter generating significantly different BCL2 promoter activities. Paraffin-embedded neoplastic and nonneoplastic tissues from 274 patients (161 still alive after a follow-up period of at least 80 months) with primary unilateral invasive breast carcinoma were investigated. Bcl-2 expression of tumor cells was shown by immunohistochemistry; nonneoplastic tissues were used for genotyping. Both the Bcl-2 expression and the (-938C>A) genotypes were correlated with the patients' survival. Kaplan-Meier curves revealed a significant association of the AA genotype with increased survival (P = 0.030) in lymph node-negative breast cancer patients, whereas no genotype effect could be observed in lymph node-positive cases. Ten-year survival rates were 88.6% for the AA genotype, 78.4% for the AC genotype, and 65.8% for the CC genotype. Multivariable Cox regression identified the BCL2 (-938CC) genotype as an independent prognostic factor for cancer-related death in lymph node-negative breast carcinoma patients (hazard ratio, 3.59; P = 0.032). Immunohistochemical Bcl-2 expression was significantly associated with the clinical outcome of lymph node-positive but not of lymph node-negative breast cancer patients. In lymph node-negative cases, the (-938C>A) SNP was both significantly related with the immunohistochemically determined level of Bcl-2 expression (P = 0.044) and the survival of patients with Bcl-2-expressing carcinomas (P = 0.006). These results suggest the (-938C>A) polymorphism as a survival prognosticator as well as indicator of a high-risk group within patients with lymph node-negative breast cancer.

The E23K and A190A variations of the KCNJ11 gene are associated with early-onset type 2 diabetes and blood pressure in the Chinese population.

PubMed

Zhuang, Langen; Zhao, Yu; Zhao, Weijing; Li, Ming; Yu, Ming; Lu, Ming; Zhang, Rong; Ge, Xiaoxu; Zheng, Taishan; Li, Can; Yin, Jun; Yin, Jingyuan; Bao, Yuqian; Liu, Limei; Jia, Weiping; Liu, Yanjun

2015-06-01

Conflicting associations between define (KCNJ11) variations and susceptibility to late-onset (>40 years old) type 2 diabetes mellitus (T2DM) have been reported in different ethnic groups. We investigated whether the E23K (G→A, rs5219) or A190A (C→T, rs5218) variations in KCNJ11 are associated with early-onset T2DM and blood pressure in the Chinese population. Case-control study of 175 unrelated Chinese patients with early-onset T2DM (age of onset <40 years old) who receive (ins+, n = 57) or do not receive insulin (ins-, n = 118), and 182 non-diabetic control subjects. PCR-direct sequencing was performed to genotype E23K and A190A; the genotypic frequencies and associations with clinical characteristics were analyzed. The genotypic frequencies of E23K-GA+AA were higher and A190A-TT was lower in the early-onset T2DM group, especially the T2D-ins+ group, compared to the non-diabetic control group (p < 0.01 or 0.05, respectively). In non-diabetic subjects, E23K-AA carriers had significantly higher 2 h plasma glucose and lower 2 h insulin than E23K-GG carriers (both p < 0.05). A190A-TT or E23K-GG carriers had higher systolic blood pressure (SBP) than CC or AA carriers in the non-diabetic control and T2DM groups (both p < 0.05). In the T2DM ins+ group, E23K-AA carriers had lower onset age and duration of diabetes and higher BMI than GG carriers, and A190A-TT carriers had higher SBP than CC carriers (all p < 0.05). The E23K-GA or AA genotypes may increase the susceptibility to early-onset T2DM, while A190A-TT may protect against early-onset T2DM. On the other hand the A190A-TT or E23K-GG genotypes may increase the risk of hypertension in the Chinese population.

Neural mechanisms of oxytocin receptor gene mediating anxiety-related temperament.

PubMed

Wang, Junping; Qin, Wen; Liu, Bing; Zhou, Yuan; Wang, Dawei; Zhang, Yunting; Jiang, Tianzi; Yu, Chunshui

2014-09-01

A common variant (rs53576) of the OXTR gene has been implicated in a number of socio-emotional phenotypes, such as anxiety-related behavior. Previous studies have demonstrated that A-allele carriers have higher levels of physiological and dispositional stress reactivity and depressive symptomatology compared to those with the GG genotype, but the mediating neural mechanisms remain poorly understood. We combined voxel-based morphometry and resting-state functional connectivity analyses in a large cohort of healthy young Chinese Han individuals to test the hypothesis that the OXTR gene polymorphism influences an anxiety-related temperamental trait, as assessed by the harm avoidance subscale from the Tridimensional Personality Questionnaire via modulating the gray matter volume and resting-state functional connectivity of the brain, especially the limbic system. We revealed that female subjects with the AA genotype showed increased harm avoidance scores relative to G-carrier females. We also found that, compared to female individuals with the GG/GA genotype, female individuals with the AA genotype exhibited significantly smaller amygdala volumes bilaterally (especially the centromedial subregion), with a trend of allele-load-dependence. Compared to female individuals with the GG/GA genotype, female subjects with the AA genotype demonstrated reduced resting-state functional coupling between the prefrontal cortex and amygdala bilaterally, also with an allele-load-dependent trend. Furthermore, the magnitude of prefrontal-amygdala coupling in the left hemisphere was positively correlated with harm avoidance scores in female subjects. Our findings highlight a possible neural pathway by which a naturally occurring variation of the OXTR gene may affect an anxiety-related temperamental trait in female subjects by modulating prefrontal-amygdala functional connectivity.

Association between BDNF rs6265 and Obesity in the Boston Puerto Rican Health Study

PubMed Central

Ma, Xian-Yong; Qiu, Wei Qiao; Smith, Caren E.; Parnell, Laurence D.; Jiang, Zong-Yong; Ordovas, Jose M.; Tucker, Katherine L.; Lai, Chao-Qiang

2012-01-01

Brain-derived neurotrophic factor (BDNF) has been associated with regulation of body weight and appetite. The goal of this study was to examine the interactions of a functional variant (rs6265) in the BDNF gene with dietary intake for obesity traits in the Boston Puerto Rican Health Study. BDNF rs6265 was genotyped in 1147 Puerto Rican adults and examined for association with obesity-related traits. Men (n = 242) with the GG genotype had higher BMI (P = 0.009), waist circumference (P = 0.002), hip (P = 0.002), and weight (P = 0.03) than GA or AA carriers (n = 94). They had twice the risk of being overweight (BMI ≥ 25) relative to GA or AA carriers (OR = 2.08, CI = 1.02–4.23, and P = 0.043). Interactions between rs6265 and polyunsaturated fatty acids (PUFA) intake were associated with BMI, hip, and weight, and n-3 : n-6 PUFA ratio with waist circumference in men. In contrast, women (n = 595) with the GG genotype had significantly lower BMI (P = 0.009), hip (P = 0.029), and weight (P = 0.027) than GA or AA carriers (n = 216). Women with the GG genotype were 50% less likely to be overweight compared to GA or AA carriers (OR = 0.05, CI = 0.27–0.91, and P = 0.024). In summary, BDNF rs6265 is differentially associated with obesity risk by sex and interacts with PUFA intake influencing obesity traits in Boston Puerto Rican men. PMID:23326649

Clinical performance of the novel DiaSorin LIAISON(®) XL murex: HBsAg Quant, HCV-Ab, HIV-Ab/Ag assays.

PubMed

Krawczyk, Adalbert; Hintze, Christian; Ackermann, Jessica; Goitowski, Birgit; Trippler, Martin; Grüner, Nico; Neumann-Fraune, Maria; Verheyen, Jens; Fiedler, Melanie

2014-01-01

The fully automated and closed LIAISON(®)XL platform was developed for reliable detection of infection markers like hepatitis B virus (HBV) surface antigen (HBsAg), hepatitis C virus (HCV) antibodies (Ab) or human immunodeficiency virus (HIV)-Ag/Ab. To date, less is known about the diagnostic performance of this system in direct comparison to the common Abbott ARCHITECT(®) platform. We compared the diagnostic performance and usability of the DiaSorin LIAISON(®)XL with the commonly used Abbott ARCHITECT(®) system. The qualitative performance of the above mentioned assays was compared in about 500 sera. Quantitative tests were performed for HBsAg-positive samples from patients under therapy (n=289) and in vitro expressed mutants (n=37). For HCV-Ab, a total number of 155 selected samples from patients chronically infected with different HCV genotypes were tested. The concordance between both systems was 99.4% for HBsAg, 98.81% for HCV-Ab, and 99.6% for HIV-Ab/Ag. The quantitative LIAISON(®)XL murex HBsAg assay detected all mutants in comparable amounts to the HBsAg wild type and yielded highly reliable HBsAg kinetics in patients treated with antiviral drugs. Dilution experiments using the 2nd International Standard for HBsAg (WHO) showed a high accuracy of this test. HCV-Ab from patients infected with genotypes 1-3 were equally detected in both systems. Interestingly, S/CO levels of HCV-Ab from patients infected with genotype 3 seem to be relatively low using both systems. The LIAISON(®)XL platform proved to be an excellent system for diagnostics of HBV, HCV, and HIV with equal performance compared to the ARCHITECT(®) system. Copyright © 2013 Elsevier B.V. All rights reserved.

Correlation between NFATC1 gene polymorphisms and congenital heart disease in children.

PubMed

Li, C-L; Niu, L; Fu, M-Y; Tian, J; Wang, Q-W; An, X-J

2017-08-01

To analyze the links between NFATC1 gene polymorphism and congenital heart disease in children. In the present study, we selected 85 children patients with congenital heart disease who were hospitalized from February 2013 to February 2015 as research subjects (observation group), and 92 healthy subjects as control group. Restriction fragment length polymorphism (RFLP) was used for analysis of NFATC1 gene in samples from each group. The distribution of NFATC1 genotype and allele between the observation group (children with congenital heart disease) and the control group showed no significant difference (p >0.05), but AA, GG genotypes, and allele frequency between pathological samples of children with congenital heart disease and the control group displayed significant difference (p <0.05) (X2 = 16.04, p <0.05; X2 = 16.29, p <0.05). Further analyses showed that AA, GG, AG genotype and allele frequency among children with congenital heart disease in observation group also showed a difference, i.e., homozygote (AA, GG) ratio in children with severe congenital heart disease is relatively high. There is a correlation between NFATC1 genes and the incidence of congenital heart disease in children, and a correlation between different genotypes and allele frequency and the incidence of the disease.

Research on the relativity between gene polymorphism and children cardiac insufficiency.

PubMed

He, X-H; Li, C-L; Ling, N; Wang, Q-W; Wang, Z-Z; An, X-J

2017-08-01

We analyzed the relationship between Mink-S27 gene polymorphism and children with cardiac insufficiency. From April 2013 to April 2015, we enrolled 73 cases of children with cardiac insufficiency for this study, and all 73 were placed in the observation group. 76 normal cases were selected for the control group. Restriction fragment length polymorphism (RFLP) was used to make polymorphism analysis of the Mink-S27. Our results showed no significant differences in Mink-S27 genotype and allele distribution in both observation and control groups (p>0.05). In lesion samples collected from children with cardiac insufficiency, we detected significant difference in AA, CC genotype frequency and allele frequency between the observation group and the control group (p< 0.05) (X2 = 15.43, p<0.05; X2  = 16.27, p<0.05). Further studies on samples obtained from both groups revealed certain differences of AA, CC, AC genotype frequency and allele frequency in the observation group. The proportion of homozygote (AA, CC) in children with severe cardiac insufficiency was relatively high. GNAS2 gene polymorphism was associated with the prevalence of cardiac insufficiency in children. And also the patients' condition was correlated to the frequency of different genotypes and alleles.

Biomarkers in the Detection of Prostate Cancer in African Americans

DTIC Science & Technology

2015-09-01

AAs. These may be inherited genetic factors, DNA mutations in the tumor or epigenetic changes secondary to or interacting with other biological changes...WA) ancestry by AIMs genotyping, while a large proportion (40%) of the AAs diagnosed with no cancer on biopsy showed more than 25% EU genetic ...African Americans showed genetic evidence of ancestry admixture; in our Birmingham AA subjects this admixture was almost entirely from European ancestors

Biomarkers in the Detection of Prostate Cancer in African Americans

DTIC Science & Technology

2015-09-01

of PrCas in AAs. These may be inherited genetic factors, DNA mutations in the tumor or epigenetic changes secondary to or interacting with other... genetic admixture. This finding suggests that in AAs, ancestry genotyping may be helpful in assessing individual PrCa risk and provide useful...identified African Americans showed genetic evidence of ancestry admixture; in our Birmingham AA subjects this admixture was almost entirely from

RECQ1 A159C Polymorphism Is Associated With Overall Survival of Patients With Resected Pancreatic Cancer: A Replication Study in NRG Oncology Radiation Therapy Oncology Group 9704

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Donghui, E-mail: dli@mdanderson.org; Moughan, Jennifer; Crane, Christopher

Purpose: To confirm whether a previously observed association between RECQ1 A159C variant and clinical outcome of resectable pancreatic cancer patients treated with preoperative chemoradiation is reproducible in another patient population prospectively treated with postoperative chemoradiation. Methods and Materials: Patients were selected, according to tissue availability, from eligible patients with resected pancreatic cancer who were enrolled on the NRG Oncology Radiation Therapy Oncology Group 9704 trial of 5-fluorouacil (5-FU)-based chemoradiation preceded and followed by 5-FU or gemcitabine. Deoxyribonucleic acid was extracted from paraffin-embedded tissue sections, and genotype was determined using the Taqman method. The correlation between genotype and overall survival wasmore » analyzed using a Kaplan-Meier plot, log-rank test, and multivariate Cox proportional hazards models. Results: In the 154 of the study's 451 eligible patients with evaluable tissue, genotype distribution followed Hardy-Weinberg equilibrium (ie, 37% had genotype AA, 43% AC, and 20% CC). The RECQ1 variant AC/CC genotype carriers were associated with being node positive compared with the AA carrier (P=.03). The median survival times (95% confidence interval [CI]) for AA, AC, and CC carriers were 20.6 (16.3-26.1), 18.8 (14.2-21.6), and 14.2 (10.3-21.0) months, respectively. On multivariate analysis, patients with the AC/CC genotypes were associated with worse survival than patients with the AA genotype (hazard ratio [HR] 1.54, 95% CI 1.07-2.23, P=.022). This result seemed slightly stronger for patients on the 5-FU arm (n=82) (HR 1.64, 95% CI 0.99-2.70, P=.055) than for patients on the gemcitabine arm (n=72, HR 1.46, 95% CI 0.81-2.63, P=.21). Conclusions: Results of this study suggest that the RECQ1 A159C genotype may be a prognostic or predictive factor for resectable pancreatic cancer patients who are treated with adjuvant 5-FU before and after 5-FU-based chemoradiation. Further study is needed in patients treated with gemcitabine to determine whether an association exists.« less

TNF-α -308G/A gene polymorphism in bullous pemphigoid and alopecia areata.

PubMed

Moravvej, Hamideh; Tabatabaei-Panah, Pardis-Sadat; Ebrahimi, Elaheh; Esmaeili, Nafiseh; Ghaderian, Sayyed Mohammad Hossein; Ludwig, Ralf J; Akbarzadeh, Reza

2018-05-11

TNF-α -308G/A polymorphism has been investigated in few studies for an association with susceptibility to bullous pemphigoid (BP) and alopecia areata (AA). Yet, these findings had so far not been independently replicated, and no data on a possible association of TNFα -308G/A polymorphism with these diseases in Iranian population were available. In the present study, a possible effect of TNF-α -308G/A variation on susceptibility to BP or AA disease was evaluated. Genomic DNA was extracted from the blood of the patients with BP and AA as well as control subjects which genotyped for the TNF-α -308 G/A polymorphism. TNF-α gene expression levels were analyzed by real-time RT-PCR. No association was observed between the TNF-α -308 G/A variation and susceptibility to BP or AA diseases in our Iranian cohort. In contrast to AA patients, expression of TNF-α gene was significantly higher in BP patients compared to control group. TNF-α gene was found to be similarly expressed in mutant and wild-type genotypes. TNF-α -308G/A polymorphism is not associated with the risk to develop of BP and AA in our Iranian cohort. Furthermore, this polymorphism is not contributed to altering the levels of gene expression in both diseases.

Polymorphisms in the HSP90AA1 5' flanking region are associated with scrapie incubation period in sheep.

PubMed

Marcos-Carcavilla, Ane; Moreno, Carole; Serrano, Magdalena; Laurent, Pascal; Cribiu, Edmond P; Andréoletti, Olivier; Ruesche, Julien; Weisbecker, Jean-Louis; Calvo, Jorge H; Moazami-Goudarzi, Katayoun

2010-07-01

Susceptibility to scrapie is mainly controlled by point mutations at the PRNP locus. However, additional quantitative trait loci (QTL) have been identified across the genome including a region in OAR18. The gene which encodes the inducible form of the cytoplasmic Hsp90 chaperone (HSP90AA1) maps within this region and seems to be associated with the resistance/susceptibility to scrapie in sheep. Here, we have analyzed several polymorphisms which were previously described in the ovine HSP90AA1 5' flanking region and in intron 10 in two naturally scrapie infected Romanov sheep populations. First, we have studied 58 ARQ/VRQ animals pertaining to the sire family where the QTL influencing scrapie incubation period in OAR18 was detected. We have found a significant association between polymorphisms localized at -660 and -528 in the HSP90AA1 5' flanking region and the scrapie incubation period. These two polymorphisms have also been studied in a second sample constituted by 62 VRQ/VRQ sheep showing an extreme incubation period. Results are concordant with the first dataset. Finally, we have studied the HSP90AA1 expression in scrapie and control animals (N = 41) with different HSP90AA1 genotypes by real time PCR on blood samples. The HSP90AA1 expression rate was equivalent in CC(-600)AA(-528) and CG(-600)AG(-528) scrapie resistant animals (ARR/ARR) and was higher in their CC(-600)AA(-528) than in their CG(-600)AG(-528) scrapie susceptible counterparts (VRQ/VRQ). Our results support the hypothesis that the ovine HSP90AA1 gene acts as a modulator of scrapie susceptibility, contributing to the observed differences in the incubation period of scrapie infected animals with the same PRNP genotype.

The Individual and Population Genetics of Antibody Immunity.

PubMed

Watson, Corey T; Glanville, Jacob; Marasco, Wayne A

2017-07-01

Antibodies (Abs) produced by immunoglobulin (IG) genes are the most diverse proteins expressed in humans. While part of this diversity is generated by recombination during B-cell development and mutations during affinity maturation, the germ-line IG loci are also diverse across human populations and ethnicities. Recently, proof-of-concept studies have demonstrated genotype-phenotype correlations between specific IG germ-line variants and the quality of Ab responses during vaccination and disease. However, the functional consequences of IG genetic variation in Ab function and immunological outcomes remain underexplored. In this opinion article, we outline interconnections between IG genomic diversity and Ab-expressed repertoires and structure. We further propose a strategy for integrating IG genotyping with functional Ab profiling data as a means to better predict and optimize humoral responses in genetically diverse human populations, with immediate implications for personalized medicine. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sensitivity and specificity of PS/AA-modified nanoparticles used in malaria detection

PubMed Central

Thiramanas, Raweewan; Jangpatarapongsa, Kulachart; Asawapirom, Udom; Tangboriboonrat, Pramuan; Polpanich, Duangporn

2013-01-01

Summary Polystyrene (PS) nanoparticle (NP) copolymerized with acrylic acid (AA) and coloured monomer, i.e. 2,3,6,7-tetra(2,2′-bithiophene)-1,4,5,8-naphthalenetetracarboxylic-N,N′-di(2-methylallyl)-bisimide (ALN8T), was synthesized via the miniemulsion polymerization. Before applying for malaria antigen detection, the blue NP was conjugated with human polyclonal malaria IgG antibody (Ab) specific to Plasmodium falciparum. For the conjugation, three methods, i.e. physical adsorption, covalent coupling and affinity binding via streptavidin (SA) and biotin interaction, were employed. The optimum ratio of Ab to NPs used in each immobilization procedure and the latex agglutination test based on the reaction between Ab conjugated NPs and malaria patient plasma were investigated. All Ab–latex conjugates provided the high sensitivity for the detection of P. falciparum malaria plasma. The highest specificity to P. falciparum was obtained from using Ab–NPs conjugated via the SA–biotin interaction. PMID:23298152

Resistance Risk Assessment of Spodoptera frugiperda (Lepidoptera: Noctuidae) and Diatraea saccharalis (Lepidoptera: Crambidae) to Vip3Aa20 Insecticidal Protein Expressed in Corn.

PubMed

Bernardi, Oderlei; Bernardi, Daniel; Amado, Douglas; Sousa, Renan S; Fatoretto, Julio; Medeiros, Fernanda C L; Conville, Jared; Burd, Tony; Omoto, Celso

2015-12-01

Transgenic Agrisure Viptera 3 corn that expresses Cry1Ab, Vip3Aa20, and EPSPS proteins and Agrisure Viptera expressing Vip3Aa20 are used for control of Spodoptera frugiperda (J.E. Smith) and Diatraea saccharalis (F.) in Brazil. To support a resistance management program, resistance risk assessment studies were conducted to characterize the dose expression of Vip3Aa20 protein and level of control against these species. The Vip3Aa20 expression in Agrisure Viptera 3 and Agrisure Viptera decreased from V6 to V10 stage of growth. However, Vip3Aa20 expression in Agrisure Viptera 3 at V6 and V10 stages was 13- and 16-fold greater than Cry1Ab, respectively. The Vip3Aa20 expression in lyophilized tissue of Agrisure Viptera 3 and Agrisure Viptera diluted 25-fold in an artificial diet caused complete larval mortality of S. frugiperda and D. saccharalis. In contrast, lyophilized tissue of Bt11 at the same dilution does not provide complete mortality of these species. Agrisure Viptera 3 and Agrisure Viptera also caused a high level of mortality against S. frugiperda and D. saccharalis. Moreover, 100% mortality was observed for S. frugiperda larvae (neonates through fifth-instar larvae) when fed in corn with the Vip trait technology. Viptera corn achieves a high level of control against S. frugiperda and D. saccharalis providing a high dose, which is an important determination to support the refuge strategy for an effective resistance management program. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The functional cytotoxic T lymphocyte-associated Protein 4 49G-to-A genetic variant and risk of pancreatic cancer.

PubMed

Yang, Ming; Sun, Tong; Zhou, Yifeng; Wang, Li; Liu, Li; Zhang, Xiaojiao; Tang, Xiaohu; Zhou, Mo; Kuang, Pengqun; Tan, Wen; Li, Hui; Yuan, Qipeng; Yu, Dianke

2012-10-01

Antitumor T lymphocytes play an essential part in immune surveillance of cancer cells. Cytotoxic T lymphocyte-associated Protein 4 (CTLA-4) is a negative regulator of T cell activation and proliferation and therefore influences immune surveillance of carcinogenesis of pancreas. Thus, this study examined the association between functional CTLA-4 49G-to-A (49G>A) single-nucleotide polymorphism and pancreatic cancer risk. Genotypes were determined in 368 patients with pancreatic cancer and 926 controls, and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. A significant increased risk of pancreatic cancer was found to be associated with the CTLA-4 49G>A single-nucleotide polymorphism. Compared with noncarriers, the OR of developing pancreatic cancer for CTLA-4 49 GA or AA carriers was 1.75 (95% CI = 1.34-2.30, P = 4.83 × 10(-5) ) or 2.54 (95% CI = 1.67-3.87, P = 1.36 × 10(-5) ), respectively. In stratified analyses, the association was more pronounced in GA and AA carriers aged ≤60 years (OR = 3.10, 95% CI = 2.15-4.47, P(interaction) = .002), smokers with GA and AA genotypes (OR = 3.92, 95% CI = 2.39-6.43, P(interaction) = .037), and drinkers with GA and AA genotypes (OR = 4.55, 95% CI = 2.65-7.82, P(interaction) = .042), compared with GG carriers. Moreover, a supermultiplicative interaction between the CTLA-4 49AA genotype and smoking plus drinking was also evident in intensifying risk of pancreatic cancer (P(interaction) = 5.64 × 10(-12) ). These results suggest that CTLA-4 49G>A polymorphism is involved in susceptibility to developing pancreatic cancer, alone and in a gene-environment interaction manner. Copyright © 2012 American Cancer Society.

The influence of CYP1A2 genotype in the blood pressure response to caffeine ingestion is affected by physical activity status and caffeine consumption level.

PubMed

Soares, Rogerio Nogueira; Schneider, Augusto; Valle, Sandra Costa; Schenkel, Paulo Cavalheiro

2018-03-06

This study aimed to investigate whether the influence of CYP1A2 genotype in the blood pressure (BP) response to caffeine ingestion was affected by physical activity status and habitual caffeine consumption. Thirty-seven participants (19-50 years old) took place in the study and were categorized according to i) genotype: CYP1A2 (AA) "fast metabolizer", and CYP1A2 (AC) "slow metabolizer"; ii) physical activity level: sedentary (S) and physically active (A); and iii) caffeine consumption level: non-habitual caffeine consumer (NC) and habitual heavy caffeine consumer (C). All groups had BP assessed before (basal) and 1 hourh after (post) caffeine ingestion (6 mg·kg -1 ). It was observed that AC genotype individuals had increased basal-DBP and post-caffeine SBP when compared to AA individuals. Additionally, acute caffeine ingestion increased SBP only in the AC group. It was also found that physical activity only modulated the BP responses to acute caffeine ingestion in AC individuals. Furthermore, the results indicated that the habitual heavy caffeine consumers AC individuals had increased basal-DBP when compared to the AA ones. Our results suggest that the influence of CYP1A2 genotype in the basal and post-caffeine BP response to caffeine ingestion is modified by physical activity status and caffeine consumption level. Copyright © 2018 Elsevier Inc. All rights reserved.

CD14 and IL18 gene polymorphisms associated with colorectal cancer subsite risks among atomic bomb survivors.

PubMed

Hu, Yiqun; Yoshida, Kengo; Cologne, John B; Maki, Mayumi; Morishita, Yukari; Sasaki, Keiko; Hayashi, Ikue; Ohishi, Waka; Hida, Ayumi; Kyoizumi, Seishi; Kusunoki, Yoichiro; Tokunaga, Katsushi; Nakachi, Kei; Hayashi, Tomonori

2015-01-01

Colorectal cancer (CRC) is a common malignancy worldwide, and chronic inflammation is a risk factor for CRC. In this study, we carried out a cohort study among the Japanese atomic bomb (A-bomb) survivor population to investigate any association between immune- and inflammation-related gene polymorphisms and CRC. We examined the effects of six single-nucleotide polymorphisms of CD14 and IL18 on relative risks (RRs) of CRC. Results showed that RRs of CRC, overall and by anatomic subsite, significantly increased with increasing radiation dose. The CD14-911A/A genotype showed statistically significant higher risks for all CRC and distal CRC compared with the other two genotypes. In addition, the IL18-137 G/G genotype showed statistically significant higher risks for proximal colon cancer compared with the other two genotypes. In phenotype-genotype analyses, the CD14-911A/A genotype presented significantly higher levels of membrane and soluble CD14 compared with the other two genotypes, and the IL18-137 G/G genotype tended to be lower levels of plasma interleukin (IL)-18 compared with the other two genotypes. These results suggest the potential involvement of a CD14-mediated inflammatory response in the development of distal CRC and an IL18-mediated inflammatory response in the development of proximal colon cancer among A-bomb survivors.

CD14 and IL18 gene polymorphisms associated with colorectal cancer subsite risks among atomic bomb survivors

PubMed Central

Hu, Yiqun; Yoshida, Kengo; Cologne, John B; Maki, Mayumi; Morishita, Yukari; Sasaki, Keiko; Hayashi, Ikue; Ohishi, Waka; Hida, Ayumi; Kyoizumi, Seishi; Kusunoki, Yoichiro; Tokunaga, Katsushi; Nakachi, Kei; Hayashi, Tomonori

2015-01-01

Colorectal cancer (CRC) is a common malignancy worldwide, and chronic inflammation is a risk factor for CRC. In this study, we carried out a cohort study among the Japanese atomic bomb (A-bomb) survivor population to investigate any association between immune- and inflammation-related gene polymorphisms and CRC. We examined the effects of six single-nucleotide polymorphisms of CD14 and IL18 on relative risks (RRs) of CRC. Results showed that RRs of CRC, overall and by anatomic subsite, significantly increased with increasing radiation dose. The CD14–911A/A genotype showed statistically significant higher risks for all CRC and distal CRC compared with the other two genotypes. In addition, the IL18–137 G/G genotype showed statistically significant higher risks for proximal colon cancer compared with the other two genotypes. In phenotype–genotype analyses, the CD14–911A/A genotype presented significantly higher levels of membrane and soluble CD14 compared with the other two genotypes, and the IL18–137 G/G genotype tended to be lower levels of plasma interleukin (IL)-18 compared with the other two genotypes. These results suggest the potential involvement of a CD14-mediated inflammatory response in the development of distal CRC and an IL18-mediated inflammatory response in the development of proximal colon cancer among A-bomb survivors. PMID:27081544

[Maturation of Cordyceps sinensis associates with alterations of fungal expressions of multiple Ophiocordyceps sinensis mutants in stroma of Cordyceps sinensis].

PubMed

Gao, Ling; Li, Xiao-hong; Zhao, Jian-qing; Lu, Ji-hong; Zhao, Jia-gang; Zhu, Jia-shi

2012-06-18

To examine maturational changes in expressions of Ophiocordyceps sinensis (O.sinensis) transition and transversion mutation genotypes in Cordyceps sinensis (C.sinensis) stroma. MassARRAY single nucleotide polymorphism (SNP) matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrum genotyping was used, and 8 SNP extension primers were designed based on the scattered, multiple point mutations of known sequences for the O.sinensis mutants within their internal transcribed spacer (ITS) segments. Of the extension primers, 5 (not capable of distinguishing between the 2 AT-biased genotypes) located in rDNA ITS1 and ITS2 regions: 067721-211, 067721-240, 067721-477, 067721-531 and 067721-581. The other 3 extension primers located in 5.8S rDNA region: 067740-324, 067740-328 and 067740-360, to distinguish between the 2 AT-biased genotypes. MS chromatograms at the 8 SNP sites showed dynamic alterations of mutant alleles in C.sinensis stroma. The allele for the AT-biased genotypes at 067721-211 site showed higher peak height than its GC-biased counterpart in the premature C.sinensis stroma, but disappeared with C.sinensis maturation. Chromatograms displayed not only the transition mutation alleles, but also transversion mutants. Some of the transversion mutation alleles displayed higher peak heights than those for GC- and AT-biased alleles, but their peak heights and detection rates tended to be decreased with C.sinensis maturation. When distinguishing between the 2 AT-biases, AB067744 and AB067740 genotype alleles co-existed in the premature C.sinensis stroma. The allele peak height for AB067744 genotype was greatly decreased with C.sinensis maturation, while that for AB067740 genotype increased. Co-existence of at least 5 transition and transversion mutant genotypes of O.sinensis and the dynamic changes in their expressions in C.sinensis stroma along with C.sinensis maturation may be of extreme importance in C.sinensis stroma germination and maturation, enabling C.sinensis to complete its life cycle.

Polymorphisms in the interferon-induced helicase (IFIH1) locus and susceptibility to Addison's disease.

PubMed

Zurawek, Magdalena; Fichna, Marta; Januszkiewicz, Danuta; Fichna, Piotr; Nowak, Jerzy

2013-02-01

The interferon-induced helicase C domain-containing protein 1 (IFIH1) gene encodes a sensor for double-stranded RNA that initiates antiviral activity against enteroviruses. Previous investigations have indicated a role for IFIH1 in autoimmunity, as common and rare polymorphisms in this gene have been associated with type 1 diabetes. We hypothesized that polymorphisms in the IFIH1 locus may play a role in the pathogenesis of autoimmune Addison's disease (AAD). We analysed the association of rs3747517, rs1990760, rs2111485 and rs13422767 single-nucleotide polymorphisms (SNPs) in the IFIH1 gene and intergenic region with AAD in a Polish cohort. The study comprised 120 patients with AAD and 689 healthy control individuals. Genotyping was performed using TaqMan genotyping assays. The major AA genotype of the coding SNP rs1990760 appeared significantly more frequently in AAD compared with healthy individuals (AG vs AA OR 0·62, 95%CI 0·40-0·95, P = 0·03). We also observed a significant difference in the distribution of the rs13422767 SNP alleles. The major G allele was more frequent in the AAD group (A vs G OR 0·65, 95%CI 0·43-0·98, P = 0·04). Both statistically significant differences, for rs1990760 and rs13422767 SNPs, did not survive the Bonferroni correction (P = 0·11 and P = 0·15, for AA genotype and G allele, respectively). Subsequently, a meta-analysis of 519 patients with AAD and 1362 controls from three different European populations was performed. Under a fixed-effect model, a pooled OR for A allele and AA genotype of rs1990760 did not display any significant increase among AAD (OR = 1·05, P = 0·56 and OR = 1·08, P = 0·50, respectively). The IFIH1 locus polymorphisms are unlikely to be associated with Addison's disease. © 2012 Blackwell Publishing Ltd.

Associations between Oxytocin Receptor (OXTR) Genotype and Elementary School Children's Likability, Dis-likability and Friendship among Classroom Peers: A Longitudinal Study.

PubMed

He, Jin; Buil, J Marieke; Koot, Hans M; van Lier, Pol A C

2018-04-27

The single nucleotide polymorphism rs53576 of the oxytocin receptor (OXTR) gene is involved in forming and maintaining relationships in various social contexts. However, this has not been studied in the childhood peer context. The present study followed 359 children (51.6% girls) from age 9 to 12 to explore associations between OXTR rs53576 genotype (i.e., AA, AG or GG genotype) and three indicators of children's relationships with peers: likability and dis-likability among, and friendship with, classroom peers. Our results showed that OXTR rs53576 was associated with likability among boys, but not with dis-likability and friendship or among girls. Boys with an A and a G allele (i.e., AG genotype) became increasingly more liked by their peers across the four-year studied period than those with two A alleles or two G alleles (i.e., AA and GG genotype). This study indicates that OXTR rs53576 genotype might influence children's peer relationships, particularly their likeability among peers. Associations between OXTR rs53576 and peer relationships may differ depending on children's sex and the specific type of peer-relationship under scrutiny.

Diffusion quantum Monte Carlo and density functional calculations of the structural stability of bilayer arsenene

NASA Astrophysics Data System (ADS)

Kadioglu, Yelda; Santana, Juan A.; Özaydin, H. Duygu; Ersan, Fatih; Aktürk, O. Üzengi; Aktürk, Ethem; Reboredo, Fernando A.

2018-06-01

We have studied the structural stability of monolayer and bilayer arsenene (As) in the buckled (b) and washboard (w) phases with diffusion quantum Monte Carlo (DMC) and density functional theory (DFT) calculations. DMC yields cohesive energies of 2.826(2) eV/atom for monolayer b-As and 2.792(3) eV/atom for w-As. In the case of bilayer As, DMC and DFT predict that AA-stacking is the more stable form of b-As, while AB is the most stable form of w-As. The DMC layer-layer binding energies for b-As-AA and w-As-AB are 30(1) and 53(1) meV/atom, respectively. The interlayer separations were estimated with DMC at 3.521(1) Å for b-As-AA and 3.145(1) Å for w-As-AB. A comparison of DMC and DFT results shows that the van der Waals density functional method yields energetic properties of arsenene close to DMC, while the DFT + D3 method closely reproduced the geometric properties from DMC. The electronic properties of monolayer and bilayer arsenene were explored with various DFT methods. The bandgap values vary significantly with the DFT method, but the results are generally qualitatively consistent. We expect the present work to be useful for future experiments attempting to prepare multilayer arsenene and for further development of DFT methods for weakly bonded systems.

Variations in CCR5, but not HFE, ELMO1, or SLC12A3, are associated with susceptibility to kidney disease in north Indian individuals with type 2 diabetes.

PubMed

Yadav, Ashok K; Kumar, Vinod; Dutta, Pinaki; Bhansali, Anil; Jha, Vivekanand

2014-11-01

Diabetic nephropathy (DN), the leading cause of end-stage renal disease worldwide, may have a genetic component. In the present study, we investigated variations in a set of genes with susceptibility to DN in a north Indian population. Four genes (HFE, ELMO1, SLC12A3, and CCR5) were selected on the basis of reported association with type 2 diabetes and nephropathy. In all, 417 diabetic subjects (215 without kidney disease [DM] and 202 with DN) and 197 healthy controls (HC) were evaluated for variations in HFE (845 G>A and 187G>C), SLC12A3 (g.34372G>A), CCR5 (59029A>G), and ELMO1 (+9170 G>A). Polymorphism analysis was performed by polymerase chain reaction-restriction fragment length polymorphism and Taqman allele discrimination assays. Significant differences were found in genotype and allelic frequency in SLC12A3 (g.34372G>A) between diabetic subjects and HC (P < 0.03). There were no differences in the SLC12A3 g.34372G>A (AA+GA) genotype between diabetic subjects with and without nephropathy. However, the CCR5 59029AA genotype and A allele were significantly more frequent in diabetics compared with the HC (P = 0.01 and 0.03, respectively) and subjects with DN versus DM (P = 0.002 and 0.01, respectively). For ELMO1 (+9170 G>A), the GG genotype frequency was higher in the diabetic versus HC group. There were no differences in the frequency of HFE-845 G>A and HFE-187G>C among the groups. This study shows that the CCR5 AA genotype is over-represented in subjects with kidney disease due to type 2 diabetes. The CCR5 59029G>A and ELMO1 (+9170 G>A) loci are more frequent, and the SLC12A3 34372 AA genotype is associated with a reduced risk of diabetes. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Polymorphism of inflammatory genes and arsenic methylation capacity are associated with urothelial carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Chia-Chang; Department of Urology, Taipei Medical University—Shuang Ho Hospital, Taipei, Taiwan; Huang, Yung-Kai

2013-10-01

Chronic exposure to arsenic can generate reactive oxidative species, which can induce certain proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8). TNF-α, IL-6 and IL-8 have been shown to be involved in the development and progression of various cancers, including bladder cancer. This study aimed to investigate the joint effect of the polymorphism of TNF-α − 308 G/A, IL-6 − 174 G/C, IL-8 − 251 T/A and urinary arsenic profiles on urothelial carcinoma (UC) risk. This study evaluated 300 pathologically-confirmed cases of UC and 594 cancer-free controls. Urinary arsenic species were detected using high-performance liquidmore » chromatography-linked hydride generator and atomic absorption spectrometry. The polymorphism of TNF-α − 308 G/A, IL-6 − 174 G/C and IL-8 − 251 T/A was determined using polymerase chain reaction-restriction fragment length polymorphism. The joint effects on UC risk were estimated by odds ratios and 95% confidence intervals using unconditional logistic regression. We found that the TNF-α − 308 A/A and IL-8 − 251 T/T polymorphisms were significantly associated with UC. Moreover, significant dose–response joint effect of TNF-α − 308 A/A or IL-8 − 251 T/T genotypes and arsenic methylation indices were seen to affect UC risk. The present results also showed a significant increase in UC risk in subjects with the IL-8 − 251 T/T genotype for each SD increase in urinary total arsenic and MMA%. In contrast, a significant decrease in UC risk was found in subjects who carried the IL-8 − 251 T/T genotype for each SD increase in DMA%. - Highlights: • Joint effect of the TNF-α -308 A/A genotype and urinary total arsenic affected UC. • Joint effect of the IL-8 -251 T/T genotype and urinary total arsenic affected UC. • Urinary total arsenic level, TNF-α -308 A/A and IL-8 -251 T/T genotype affected UC.« less

The Effects of Genetic Variation in FTO rs9939609 on Obesity and Dietary Preferences in Chinese Han Children and Adolescents

PubMed Central

Yang, Min; Xu, Yuyang; Liang, Li; Fu, Junfen; Xiong, Feng; Liu, Geli; Gong, Chunxiu; Luo, Feihong; Chen, Shaoke; Xu, Chunxiao; Zhang, Dandan; Li, Zhengli; Zhang, Shuai; Zhang, Yan; Wang, Hao; Zhu, Yimin

2014-01-01

The association of the rs9939609 single nucleotide polymorphism in FTO gene with obesity has been extensively investigated in studies of populations of European, African, and Asian ancestry. However, inconsistent results have been reported in Asian populations, and the relationship of FTO variation and dietary behaviors has only rarely been examined in Chinese children and adolescents. The aim of this study was to assess the association of rs9939609 with obesity and dietary preferences in childhood in a Chinese population. Epidemiological data including dietary preferences were collected in interviews using survey questionnaires, and rs9939609 genotype was determined by real-time PCR. The associations of rs9939609 genotypes with obesity and dietary preferences were analyzed by multivariate logistic regression using both additive and dominant models. The results showed that subjects with a TA or AA genotype had an increased risk of obesity compared with the TT participants; the odds ratios (ORs) were 1.47 (95% CI: 1.25–1.71, P = 1.73×10−6), and 3.32 (95% CI: 2.01–5.47, P = 2.68×10−6), respectively. After adjusting for age and gender, body mass index, waist circumference, hip circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose, triglycerides, and low-density lipoprotein cholesterol were higher, and high-density lipoprotein cholesterol was lower in TA and AA participants than in those with the TT genotype. After additionally controlling for body mass index, the association remained significant only for systolic blood pressure (P = 0.005). Compared with TT participants, those with the AA genotype were more likely to prefer a meat-based diet (OR = 2.81, 95% CI: 1.52–5.21). The combined OR for obesity in participants with TA/AA genotypes and preference for a meat-based diet was 4.04 (95% CI: 2.8–5.81) compared with the TT participants who preferred a plant-based diet. These findings indicate the genetic variation of rs9939609 is associated with obesity and dietary preferences in Chinese children and adolescents. PMID:25110886

NOS3 genotype-dependent correlation between blood pressure and physical activity.

PubMed

Kimura, Tomomi; Yokoyama, Tetsuji; Matsumura, Yasuhiro; Yoshiike, Nobuo; Date, Chigusa; Muramatsu, Masaaki; Tanaka, Heizo

2003-02-01

Endothelium-dependent vasorelaxation plays an important role in reduction of blood pressure and is mediated through release of nitric oxide (NO), which is generated by constitutively expressed endothelial nitric oxide synthase (NOS3). Exercise also augments NO release and has been recommended for primary prevention and improvement of hypertension, but individual responses are highly variable. We therefore postulated that genetic polymorphisms of NOS3 might interact with physical activity level to differentially influence blood pressure level. We genotyped 832 healthy Japanese (mean age of 54.4+/-8.6 years, 372 men and 460 women) for a polymorphism of NOS3 in intron 4 (ecNOS4a/b), using the polymerase chain reaction method, and scored their habitual physical activity level by using the rate of energy expenditure per resting metabolic rate through an interview according to a semiquantitative assessment method. Only in the subjects who had the rarer a allele (aa+ba type), systolic blood pressure was found to be inversely correlated with physical activity level (P for linear trend=0.0496, for interaction=0.0071). Eventually, this polymorphism was significantly associated with the prevalence of systolic hypertension only in the subjects who were in the lowest tertile of physical activity level (OR=2.4, 95% CI, 1.1 to 5.6, P for interaction=0.0474). In the present study, we found a significant interaction between the genotype and physical activity level on systolic blood pressure. These results might allow a better understanding of the mechanism to improve hypertension by exercise and to thereby reduce the risk of cardiovascular disease.

MLH1-93 G/a polymorphism is associated with MLH1 promoter methylation and protein loss in dysplastic sessile serrated adenomas with BRAFV600E mutation.

PubMed

Fennell, Lochlan J; Jamieson, Saara; McKeone, Diane; Corish, Tracie; Rohdmann, Megan; Furner, Tori; Bettington, Mark; Liu, Cheng; Kawamata, Futoshi; Bond, Catherine; Van De Pols, Jolieke; Leggett, Barbara; Whitehall, Vicki

2018-01-05

Sessile serrated adenomas with BRAF mutation progress rapidly to cancer following the development of dysplasia (SSAD). Approximately 75% of SSADs methylate the mismatch repair gene MLH1, develop mismatch repair deficiency and the resultant cancers have a good prognosis. The remaining SSADs and BRAF mutant traditional serrated adenomas (TSA) develop into microsatellite stable cancers with a poor prognosis. The reason for this dichotomy is unknown. In this study, we assessed the genotypic frequency of the MLH1-93 polymorphism rs1800734 in SSADs and TSAs to determine if the uncommon variant A allele predisposes to MLH1 promoter hypermethylation. We performed genotyping for the MLH1-93 polymorphism, quantitative methylation specific PCR, and MLH1 immunohistochemistry on 124 SSAD, 128 TSA, 203 BRAF mutant CRCs and 147 control subjects with normal colonoscopy. The minor A allele was significantly associated with a dose dependent increase in methylation at the MLH1 promoter in SSADs (p = 0.022). The AA genotype was only observed in SSADs with MLH1 loss. The A allele was also overrepresented in BRAF mutant cancers with MLH1 loss. Only one of the TSAs showed loss of MLH1 and the overall genotype distribution in TSAs did not differ from controls. The MLH1-93 AA genotype is significantly associated with promoter hypermethylation and MLH1 loss in the context of SSADs. BRAF mutant microsatellite stable colorectal cancers with the AA genotype most likely arise in TSAs since the A allele does not predispose to methylation in this context.

Cyclin D1 G870A polymorphism: Association with uterine leiomyoma risk and in silico analysis

PubMed Central

Salimi, Saeedeh; Shahrakipour, Mahnaz; Hajizadeh, Azam; Mokhtari, Mojgan; Mousavi, Mahdieh; Teimoori, Batool; Yaghmaei, Minoo

2017-01-01

Uterine leiomyoma (UL) is the most common benign tumor causing considerable morbidity during the reproductive years in women. Cyclin D1 (CCND1) is a cell cycle regulatory protein that is required for the G1 phase, and increased expression levels of this protein may affect tumorigenesis. The present study aimed to assess the possible effect of the CCND1 G870A polymorphism on UL susceptibility. A total of 154 women with UL and 197 healthy women who were age-, body mass index (BMI)- and ethnicity-matched were genotyped for the CCND1 G870A (rs9344) polymorphism using the polymerase chain reaction-restriction fragment length polymorphism method. The effects of G870A transition on the structure of mRNA and proteins of CCND1 was evaluated using bioinformatics tools. The frequency of the CCND1 870AA genotype was significantly higher in women with UL compared with the control subjects, and the risk of UL was 1.4-fold higher in women with the AA genotype when compared with the GG genotype before and after adjusting for age, BMI, and ethnicity [odds ratio (OR), 1.4; 95% confidence interval (CI), 1.1–2 (P=0.02)]. The frequency of CCND1 870GA genotype was not significantly different between the two groups. The frequency of the CCND1 870A allele was significantly higher in the women with UL when compared with the control subjects (57 vs. 48%; P=0.02). The in silico analysis revealed that the G870A transition may fundamentally alter the structure of the CCND1-mRNA. Thus, the CCND1 870AA genotype was associated with UL susceptibility in a sample of women from the southeast of Iran. PMID:28357079

SNP rs2071095 in LincRNA H19 is associated with breast cancer risk.

PubMed

Cui, Ping; Zhao, Yanrui; Chu, Xinlei; He, Na; Zheng, Hong; Han, Jiali; Song, Fengju; Chen, Kexin

2018-05-08

An increasing number of long intergenic non-coding RNAs (lincRNAs) appear to play critical roles in cancer development and progression. To assess the association between SNPs that reside in regions of lincRNAs and breast cancer risk, we performed a large case-control study in China. We carried out a two-stage case-control study including 2881 breast cancer cases and 3220 controls. In stage I, we genotyped 17 independent (r 2  < 0.5) SNPs located in 6 tumor-related lincRNAs by using the TaqMan platform. In stage II, SNPs potentially associated with breast cancer risk were replicated in an independent population. Quantitative real-time PCR was used to measure H19 levels in tissues from 228 breast cancer patients with different genotypes. We identified 2 SNPs significantly associated with breast cancer risk in stage I (P < 0.05), but not significantly replicated in stage II. We combined the data from stage I and stage II, and found that, compared with the rs2071095 CC genotype, AA and CA + AA genotypes were associated with significantly decreased risk of breast cancer (adjusted OR 0.83, 95% CI 0.69-0.99; adjusted OR 0.88, 95% CI 0.80-0.98, respectively). Stratified analyses showed that rs2071095 was associated with breast cancer risk in estrogen receptor (ER)-positive patients (P = 0.002), but not in ER-negative ones (P = 0.332). Expression levels of H19 in breast cancer cases with AA genotype were significantly lower than those with CC genotype. We identified that rs2071095 may contribute to the susceptibility of breast cancer in Chinese women via affecting H19 expression. The mechanisms underlying the association remain to be investigated.

Influence of Combined Methionine Synthase (MTR 2756A > G) and Methylenetetrahydrofolate Reductase (MTHFR 677C > T) Polymorphisms to Plasma Homocysteine Levels in Korean Patients with Ischemic Stroke

PubMed Central

Kim, Ok Joon; Hong, Sun Pyo; Ahn, Jung Yong; Hong, Seung Ho; Hwang, Tae Sun; Kim, Soo Ok; Yoo, Wangdon; Oh, Doyeun

2007-01-01

Purpose Methionine synthase (MTR) and 5,10-methylenetetrahydrofolate reductase (MTHFR) are the main regulatory enzymes for homocysteine metabolism. The present case-control study was conducted to determine whether there is an association between the MTR 2756A > G or MTHFR 677C > T polymorphism and plasma homocysteine concentration in Korean subjects with ischemic stroke. Materials and Methods DNA samples of 237 patients who had an ischemic stroke and 223 age and sex-matched controls were studied. MTR 2756A > G and MTHFR 677C > T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results Frequencies of mutant alleles for MTR and MTHFR polymorphisms were not significantly different between the controls and cases. The patient group, however, had significantly higher homocysteine concentrations of the MTR 2756AA and MTHFR 677TT genotypes than the control group (p = 0.04 for MTR, p = 0.01 for MTHFR). The combined MTR 2756AA and MTHFR 677TT genotype (p = 0.04) and the homocysteine concentrations of the patient group were also higher than those of the controls. In addition, the genotype distribution was significant in the MTHFR 677TT genotype (p = 0.008) and combined MTR 2756AA and MTHFR 677TT genotype (p = 0.03), which divided the groups into the top 20% and bottom 20% based on their homocysteine levels. Conclusion The results of the present study demonstrate that the MTR 2756A > G and MTHFR 677C > T polymorphisms interact with elevated total homocysteine (tHcy) levels, leading to an increased risk of ischemic stroke. PMID:17461517

African Ancestry Influences CCR5 –2459G>A Genotype-Associated Virologic Success of Highly Active Antiretroviral Therapy

PubMed Central

Cheruvu, Vinay K.; Igo, Robert P.; Jurevic, Richard J.; Serre, David; Zimmerman, Peter A.; Rodriguez, Benigno; Mehlotra, Rajeev K.

2014-01-01

Introduction In a North American, HIV-positive, highly active antiretroviral therapy (HAART)-treated, adherent cohort of self-identified white and black patients, we previously observed that chemokine (C-C motif) receptor 5 (CCR5) –2459G>A genotype had a strong association with time to achieve virologic success (TVLS) in black but not in white patients. Methods Using 128 genome-wide ancestry informative markers, we performed a quantitative assessment of ancestry in these patients (n = 310) to determine (1) whether CCR5 –2459G>A genotype is still associated with TVLS of HAART when ancestry, not self-identified race, is considered and (2) whether this association is influenced by varying African ancestry. Results We found that the interaction between CCR5 –2459G>A genotype and African ancestry (≤0.125 vs. ≥0.425 and <0.71 vs. ≥0.71) was significantly associated with TVLS (GG compared with AA, P = 0.044 and 0.018, respectively). Furthermore, the association between CCR5 –2459G>A genotype and TVLS was stronger in patients with African ancestry ≥0.71 than in patients with African ancestry ≥0.452, in both Kaplan-Meier (log-rank P = 0.039 and 0.057, respectively, for AA, GA, and GG) and Cox proportional hazards regression (relative hazard for GG compared with AA 2.59 [95% CI, 1.27–5.22; P = 0.01] and 2.26 [95% CI, 1.18–4.32; P = 0.01], respectively) analyses. Conclusions We observed that the association between CCR5 –2459G>A genotype and TVLS of HAART increased with stronger African ancestry. Understanding the genomic mechanisms by which African ancestry influences this association is critical, and requires further studies. PMID:24714069

Effect Of G2706A and G1051A polymorphisms of the ABCA1 gene on the lipid, oxidative stress and homocystein levels in Turkish patients with polycystıc ovary syndrome

PubMed Central

2011-01-01

Background Obesity, insulin resistance and hyperandrogenism, crucial parameters of Polycystic ovary syndrome (PCOS) play significant pathophysiological roles in lipidemic aberrations associated within the syndrome. Parts of the metabolic syndrome (low HDL and insulin resistance) appeared to facilitate the association between PCOS and coronary artery disease, independently of obesity. ABCA1 gene polymorphism may be altered this components in PCOS patients. In this study, we studied 98 PCOS patients and 93 healthy controls. All subjects underwent venous blood drawing for complete hormonal assays, lipid profile, glucose, insulin, malondialdehyde, nitric oxide, disulfide levels and ABCA genetic study. Results In PCOS group fasting glucose, DHEAS, 17-OHP, free testosterone, total-cholesterol, triglyceride, LDL-cholesterol and fibrinogen were significantly different compare to controls. The genotype ABCA G2706A distribution differed between the control group (GG 60.7%, GA 32.1%, AA 7.1%) and the PCOS patients (GG 8.7%, GA 8.7%, AA 76.8%). The frequency of the A allele (ABCAG2706A) was higher in PCOS patients than control group with 13,0% and 23,2%, respectively. In this study, the homocystein and insulin levels were significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes. Conclusions We found higher percentage of AA genotype and A allele of ABCA G2706A in PCOS patients compare to controls. The fasting insulin and homocystein levels were significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes. PMID:22035022

Application of Bogolyubov's theory of weakly nonideal Bose gases to the A+A, A+B, B+B reaction-diffusion system

NASA Astrophysics Data System (ADS)

Konkoli, Zoran

2004-01-01

Theoretical methods for dealing with diffusion-controlled reactions inevitably rely on some kind of approximation, and to find the one that works on a particular problem is not always easy. Here the approximation used by Bogolyubov to study a weakly nonideal Bose gas, referred to as the weakly nonideal Bose gas approximation (WBGA), is applied in the analysis of three reaction-diffusion models: (i) A+A→Ø, (ii) A+B→Ø, and (iii) A+A,B+B,A+B→Ø (the ABBA model). Two types of WBGA are considered, the simpler WBGA-I and the more complicated WBGA-II. All models are defined on the lattice to facilitate comparison with computer experiment (simulation). It is found that the WBGA describes the A+B reaction well, it reproduces the correct d/4 density decay exponent. However, it fails in the case of the A+A reaction and the ABBA model. (To cure the deficiency of WBGA in dealing with the A+A model, a hybrid of the WBGA and Kirkwood superposition approximations is suggested.) It is shown that the WBGA-I is identical to the dressed-tree calculation suggested by Lee [J. Phys. A 27, 2633 (1994)], and that the dressed-tree calculation does not lead to the d/2 density decay exponent when applied to the A+A reaction, as normally believed, but it predicts the d/4 decay exponent. Last, the usage of the small n0 approximation suggested by Mattis and Glasser [Rev. Mod. Phys. 70, 979 (1998)] is questioned if used beyond the A+B reaction-diffusion model.

Genetic susceptibility to type 1 diabetes in the intracellular pathway of antigen processing - a subject review and cross-study comparison.

PubMed

Sia, Charles; Weinem, Michael

2005-01-01

Ligand binding grooves of MHC class I molecules are able to load a panel of endogenous peptides of varying length and sequence derived from self or foreign origin to activate or deactivate cytotoxic CD8(+) T cells. Peptides are assembled with class I molecules by pathways that are either dependent or independent of transport by ABC proteins (TAP) and degradation in the immunoproteasome by its subunits LMP2 and LMP7. Those peptides that require TAP and LMP treatment appear to be subject to control and optimization by TAP for proper customizing and efficient presentation. Therefore, allelic variations in the coding sequences of TAP and LMP were suspected for a long time to be responsible for improper antigen processing, interruption of self-peptide presentation and reduced cell surface expression of MHC class I molecules resulting in the activation of autoreactive CD8(+) T cells. In this article we reviewed the controversial findings regarding the role of TAP and LMP genes in autoimmune diabetes and reevaluated data of eleven separate studies in a cross-study analysis by genotype and HLA haplotype matching. We could confirm previous results by showing that TAP2*651-A/F and TAP2*687-A/A are significantly associated with disease, independently of linkage disequilibrium (LD). LMP2-R/H surprisingly seems to be primarily disease-conferring although a weak association with DR4 serotypes can be observed. Our analysis also suggests that LMP7-B/B, TAP1-A/A and TAP2*687-A/B are the protective genotypes and that these associations are not secondary to LD with DRB1. Consequently, intracellular antigen processing associated with TAP- and proteasome-dependent pathways seems to be a critical element in T cell selection for the retention of a balanced immunity.

Association between decreased vitamin levels and MTHFR, MTR and MTRR gene polymorphisms as determinants for elevated total homocysteine concentrations in pregnant women.

PubMed

Barbosa, P R; Stabler, S P; Machado, A L K; Braga, R C; Hirata, R D C; Hirata, M H; Sampaio-Neto, L F; Allen, R H; Guerra-Shinohara, E M

2008-08-01

To examine the association between methylenetetrahydrofolate reductase (MTHFR) (C677T and A1298C), methionine synthase (MTR) A2756G and methionine synthase reductase (MTRR) A66G gene polymorphisms and total homocysteine (tHcy), methylmalonic acid (MMA) and S-adenosylmethionine/S-adenosylhomocysteine (SAM/SAH) levels; and to evaluate the potential interactions with folate or cobalamin (Cbl) status. Two hundred seventy-five healthy women at labor who delivered full-term normal babies. Cbl, folate, tHcy, MMA, SAM and SAH were measured in serum specimens. The genotypes for polymorphisms were determined by PCR-restriction fragment length polymorphism (RFLP). Serum folate, MTHFR 677T allele and MTR 2756AA genotypes were the predictors of tHcy levels in pregnant women. Serum Cbl and creatinine were the predictors of SAM/SAH ratio and MMA levels, respectively. The gene polymorphisms were not determinants for MMA levels and SAM/SAH ratios. Low levels of serum folate were associated with elevated tHcy in pregnant women, independently of the gene polymorphisms. In pregnant women carrying MTHFR 677T allele, or MTHFR 1298AA or MTRR 66AA genotypes, lower Cbl levels were associated with higher levels of tHcy. Lower SAM/SAH ratio was found in MTHFR 677CC or MTRR A2756AA genotypes carriers when Cbl levels were lower than 142 pmol/l. Serum folate and MTHFR C677T and MTR A2576G gene polymorphisms were the determinants for tHcy levels. The interaction between low levels of serum Cbl and MTHFR (C677T or A1298C) or MTRR A66G gene polymorphisms was associated with increased tHcy.

Functional Interaction Map of Lyssavirus Phosphoprotein: Identification of the Minimal Transcription Domains

PubMed Central

Jacob, Yves; Real, Eléonore; Tordo, Noël

2001-01-01

Lyssaviruses, the causative agents of rabies encephalitis, are distributed in seven genotypes. The phylogenetically distant rabies virus (PV strain, genotype 1) and Mokola virus (genotype 3) were used to develop a strategy to identify functional homologous interactive domains from two proteins (P and N) which participate in the viral ribonucleoprotein (RNP) transcription-replication complex. This strategy combined two-hybrid and green fluorescent protein–reverse two-hybrid assays in Saccharomyces cerevisiae to analyze protein-protein interactions and a reverse genetic assay in mammalian cells to study the transcriptional activity of the reconstituted RNP complex. Lyssavirus P proteins contain two N-binding domains (N-BDs), a strong one encompassing amino acid (aa) 176 to the C terminus and a weak one in the 189 N-terminal aa. The N-terminal portion of P (aa 52 to 189) also contains a homomultimerization site. Here we demonstrate that N-P interactions, although weaker, are maintained between proteins of the different genotypes. A minimal transcriptional module of the P protein was obtained by fusing the first 60 N-terminal aa containing the L protein binding site to the C-terminal strong N-BD. Random mutation of the strong N-BD on P protein identified three highly conserved K residues crucial for N-P interaction. Their mutagenesis in full-length P induced a transcriptionally defective RNP. The analysis of homologous interactive domains presented here and previously reported dissections of the P protein allowed us to propose a model of the functional interaction network of the lyssavirus P protein. This model underscores the central role of P at the interface between L protein and N-RNA template. PMID:11559793

CD209-336A/G promotor polymorphism and its clinical associations in sickle cell disease Egyptian Pediatric patients.

PubMed

Afifi, Rasha Abdel-Raouf; Kamal, Dina; Sayed, Riham El; Ekladious, Sherif M M; Shaheen, Gehan H; Yousry, Sherif M; Hussein, Rania Elsayed

2018-06-01

To detect the frequency of CD209 A>G polymorphism in sickle cell disease (SCD) Egyptian patients and to evaluate the use of CD209 A>G polymorphism as a genetic predictor of SCD clinical heterogeneity. A total of 100 Egyptian children with SCD and 100 Egyptian controls were tested for CD209 A>G polymorphism and were followed up prospectively between June 2012 and December 2014. Comparison of CD209 A>G polymorphism among cases and controls did not show statistically significant difference (p = .742). In addition, comparison of the allelic frequency did not show statistically significant difference (p = .738). Infections occurred more frequently among the heterozygous genotype (AG; 60.5%) and homozygous genotype (GG; 75%) patients than among the wild (AA) genotype (24.1%; p < .001). The use of hydroxyurea treatment was significantly higher among the wild (AA) genotype (47%) than the heterozygous (AG; 21%) and homozygous (GG; 5%) genotypes (p = .003). We found no significant difference between our population of Egyptian SCD cases and controls regarding CD209 A>G polymorphism. Infections occurred more frequently among the heterozygous genotype (AG) and homozygous genotype (GG) patients. Copyright © 2017. Published by Elsevier Ltd.

Regulatory role of Cdx-2 and Taq I polymorphism of vitamin D receptor gene on chemokine expression in pulmonary tuberculosis.

PubMed

Harishankar, M; Selvaraj, P

2016-06-01

Vitamin D receptor (VDR) gene variants have been shown to be regulating the immune response in tuberculosis. We studied the regulatory role of VDR promoter Cdx-2 and 3'UTR TaqI gene variants on chemokine levels from culture filtrate antigen (CFA) stimulated with or without 1,25(OH)2D3 treated peripheral blood mononuclear cells of 50 pulmonary tuberculosis patients (PTB) and 51 normal healthy controls (HCs). In CFA with 1,25(OH)2D3 treated cultures, the MIP-1α, MIP-1β, RANTES levels were significantly decreased in Cdx-2 AA genotype compared to GG genotype, while a significantly increased MIG level was observed in Cdx-2 AA genotype (p<0.05). In TaqI polymorphism, tt genotype significantly decreased MIP-1β and RANTES levels compared to TT genotype. Moreover, a significantly increased level of IP-10 and MIG was observed in TaqI tt genotype compared with TT genotype (p<0.05). The results suggests that the 1,25(OH)2D3 may alter the chemokine response through the VDR polymorphic variants during infection. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

High proportion of subgroup A' (genotype A) among Brazilian isolates of Hepatitis B virus.

PubMed

Araujo, N M; Mello, F C A; Yoshida, C F T; Niel, C; Gomes, S A

2004-07-01

Hepatitis B virus (HBV) genotype A has been divided recently into two subgroups, designated A-A' (genotype A excluding A') and A'. Isolates belonging to subgroup A' have been identified in Africa. A new genotyping method, based on PCR amplification of the pre-S/S genome region and subsequent restriction fragment length polymorphism (RFLP) analysis, was developed, that established a correlation between RFLP subtypes and subgroups within genotype A. To investigate the occurrence of subgroup A' in South America, 119 Brazilian HBV isolates were analyzed. Ninety-three (78%) of them belonged to genotype A, with three predominating RFLP subtypes: 44 (37%) isolates were classified as AI, 30 (25%) were AII, and 18 (15%) were AIII. Pre-S/S nucleotide sequences of 15 genotype A isolates were determined. Phylogenetic analysis performed with these 15 and an additional 41 sequences revealed that isolates AI and AII clustered in subgroup A', whereas isolates AIII were classified into subgroup A-A'. The correlation RFLP subtypes-subgroups was confirmed by the presence of amino acid residues specific for subgroup A' in the surface antigens and polymerase of isolates AI and AII. The high proportion (63%) of isolates from subgroup A' suggested an African origin for a large number of Brazilian HBVs.

[Association of vitamin D receptor gene polymorphisms with mild cognitive impairment among elderly ethnic Uygurs].

PubMed

Zhou, Xiaohui; Zhu, Meisheng; Ma, Li; Miao, Haijun

2015-12-01

To assess the association of vitamin D receptor gene (VDR) Apa I, Bsm I genotypes and allele frequencies and mild cognitive impairment (MCI) among elderly ethnic Uygurs from Xinjiang, China. The polymorphisms of the VDR genotypes (Apa I and Bsm I) were analyzed by the SNaPshot method in 124 MCI patients and 124 controls. Factors which can increase the risk for MCI have included the A allele of the Apa I polymorphism [OR=1.62, 95%CI(1.13-2.31)] and the AA genotype [OR=3.49, 95% CI(1.57-7.74)], the T allele of the Bsm I polymorphism [OR=1.94, 95%CI(1.24-3.05)], higher triglyceride and systolic blood pressure levels. Polymorphisms of the VDR gene including the A allele and AA genotype of Apa I, and the T allele of Bsm I are probably associated with MCI among elderly ethnic Uygurs, and so are higher levels of triglyceride and systolic blood pressure.

Increased Virulence and Competitive Advantage of a/α Over a/a or α/α Offspring Conserves the Mating System of Candida albicans

PubMed Central

Lockhart, Shawn R.; Wu, Wei; Radke, Joshua B.; Zhao, Rui; Soll, David R.

2005-01-01

The majority of Candida albicans strains in nature are a/α and must undergo homozygosis to a/a or α/α to mate. Here we have used a mouse model for systemic infection to test the hypothesis that a/α strains predominate in nature because they have a competitive advantage over a/a and α/α offspring in colonizing hosts. Single-strain injection experiments revealed that a/α strains were far more virulent than either their a/a or α/α offspring. When equal numbers of parent a/α and offspring a/a or α/α cells were co-injected, a/α always exhibited a competitive advantage at the time of extreme host morbidity or death. When equal numbers of an engineered a/a/α2 strain and its isogenic a/a parent strain were co-injected, the a/a/α2 strain exhibited a competitive advantage at the time of host morbidity or death, suggesting that the genotype of the mating-type (MTL) locus, not associated genes on chromosome 5, provides a competitive advantage. We therefore propose that heterozygosity at the MTL locus not only represses white-opaque switching and genes involved in the mating process, but also affects virulence, providing a competitive advantage to the a/α genotype that conserves the mating system of C. albicans in nature. PMID:15695357

Increased virulence and competitive advantage of a/alpha over a/a or alpha/alpha offspring conserves the mating system of Candida albicans.

PubMed

Lockhart, Shawn R; Wu, Wei; Radke, Joshua B; Zhao, Rui; Soll, David R

2005-04-01

The majority of Candida albicans strains in nature are a/alpha and must undergo homozygosis to a/a or alpha/alpha to mate. Here we have used a mouse model for systemic infection to test the hypothesis that a/alpha strains predominate in nature because they have a competitive advantage over a/a and alpha/alpha offspring in colonizing hosts. Single-strain injection experiments revealed that a/alpha strains were far more virulent than either their a/a or alpha/alpha offspring. When equal numbers of parent a/alpha and offspring a/a or alpha/alpha cells were co-injected, a/alpha always exhibited a competitive advantage at the time of extreme host morbidity or death. When equal numbers of an engineered a/a/alpha2 strain and its isogenic a/a parent strain were co-injected, the a/a/alpha2 strain exhibited a competitive advantage at the time of host morbidity or death, suggesting that the genotype of the mating-type (MTL) locus, not associated genes on chromosome 5, provides a competitive advantage. We therefore propose that heterozygosity at the MTL locus not only represses white-opaque switching and genes involved in the mating process, but also affects virulence, providing a competitive advantage to the a/alpha genotype that conserves the mating system of C. albicans in nature.

Signaling Pathways Related to Protein Synthesis and Amino Acid Concentration in Pig Skeletal Muscles Depend on the Dietary Protein Level, Genotype and Developmental Stages

PubMed Central

Liu, Yingying; Li, Fengna; Kong, Xiangfeng; Tan, Bie; Li, Yinghui; Duan, Yehui; Blachier, François; Hu, Chien-An A.; Yin, Yulong

2015-01-01

Muscle growth is regulated by the homeostatic balance of the biosynthesis and degradation of muscle proteins. To elucidate the molecular interactions among diet, pig genotype, and physiological stage, we examined the effect of dietary protein concentration, pig genotype, and physiological stages on amino acid (AA) pools, protein deposition, and related signaling pathways in different types of skeletal muscles. The study used 48 Landrace pigs and 48 pure-bred Bama mini-pigs assigned to each of 2 dietary treatments: lower/GB (Chinese conventional diet)- or higher/NRC (National Research Council)-protein diet. Diets were fed from 5 weeks of age to respective market weights of each genotype. Samples of biceps femoris muscle (BFM, type I) and longissimus dorsi muscle (LDM, type II) were collected at nursery, growing, and finishing phases according to the physiological stage of each genotype, to determine the AA concentrations, mRNA levels for growth-related genes in muscles, and protein abundances of mechanistic target of rapamycin (mTOR) signaling pathway. Our data showed that the concentrations of most AAs in LDM and BFM of pigs increased (P<0.05) gradually with increasing age. Bama mini-pigs had generally higher (P<0.05) muscle concentrations of flavor-related AA, including Met, Phe, Tyr, Pro, and Ser, compared with Landrace pigs. The mRNA levels for myogenic determining factor, myogenin, myocyte-specific enhancer binding factor 2 A, and myostatin of Bama mini-pigs were higher (P<0.05) than those of Landrace pigs, while total and phosphorylated protein levels for protein kinase B, mTOR, and p70 ribosomal protein S6 kinases (p70S6K), and ratios of p-mTOR/mTOR, p-AKT/AKT, and p-p70S6K/p70S6K were lower (P<0.05). There was a significant pig genotype-dependent effect of dietary protein on the levels for mTOR and p70S6K. When compared with the higher protein-NRC diet, the lower protein-GB diet increased (P<0.05) the levels for mTOR and p70S6K in Bama mini-pigs, but repressed (P<0.05) the level for p70S6K in Landrace pigs. The higher protein-NRC diet increased ratio of p-mTOR/mTOR in Landrace pigs. These findings indicated that the dynamic consequences of AA profile and protein deposition in muscle tissues are the concerted effort of distinctive genotype, nutrient status, age, and muscle type. Our results provide valuable information for animal feeding strategy. PMID:26394157

The miR-449b polymorphism, rs10061133 A>G, is associated with premature ovarian insufficiency.

PubMed

Pan, Hong; Chen, Beili; Wang, Jing; Wang, Xi; Hu, Ping; Wu, Shinan; Liu, Yunyun; Xu, Zuying; Zhang, Wei; Wang, Binbin; Cao, Yunxia

2016-09-01

To determine if the miR-449b polymorphism, rs10061133 A>G, is associated with premature ovarian insufficiency (POI) pathogenesis. From January 2011 to December 2014, a total of 148 individuals with POI and 225 age-matched controls were collected from the Center for Reproductive Medicine, 1st Affiliated Hospital of Anhui Medical University (Hefei, China). Genotyping of miR-449b rs1006113 was performed using matrix-assisted laser desorption ionization time-of-flight-based mass spectrometry. Rs10061133 A>G is a highly conserved SNP locus in the mature area of miR-449b. Association analysis shows that the rs10061133 AA genotype is a risk factor for POI. Our study provides the first evidence that the miR-449b rs10061133 AA genotype is associated with POI risk.

Molecular evidence for the existence of lipopolysaccharide-induced TNF-alpha factor (LITAF) and Rel/NF-kB pathways in disk abalone (Haliotis discus discus).

PubMed

De Zoysa, Mahanama; Nikapitiya, Chamilani; Oh, Chulhong; Whang, Ilson; Lee, Jae-Seong; Jung, Sung-Ju; Choi, Cheol Young; Lee, Jehee

2010-01-01

The lipopolysaccharide-induced TNF-alpha factor (LITAF) and Rel family nuclear factor kappaB (Rel/NF-kB) are two important transcription factors which play major roles in the regulating inflammatory cytokine, apoptosis and immune related genes. Here, we report the discovery of disk abalone LITAF (AbLITAF) and Rel/NF-kB (AbRel/NF-kB) homologues and their immune responses. Full-length cDNA of AbLITAF consists of 441 bp open reading frame (ORF) that translates into putative peptide of 147 aa. Analysis of AbLITAF sequence showed it has characteristic LITAF (Zn(+2)) binding domain with two CXXC motifs. Phylogenetic analysis results further revealed that AbLITAF is a member of LITAF family. AbRel/NF-kB is 584 aa protein that contains several characteristic motifs including Rel homology domain (RHD), Rel protein signature, DNA binding motif, nuclear localization signal (NLS) and transcription factor immunoglobulin - like fold (TIG) similar to their invertebrate and vertebrate counterparts. Tissue specific analysis results showed that both AbLITAF and AbRel/NF-kB mRNA was expressed ubiquitously in all selected tissues in constitutive manner. However, constitutive expression of AbLITAF was higher than AbRel/NF-kB in all tissues except mantle. Upon immune challenge by bacteria (Vibrio alginolyticus, Vibrio parahemolyticus and Lysteria monocytogenes) and viral hemoragic septicemia virus (VHSV), AbLITAF showed the significant up-regulation in gills while AbRel/NF-kB transcription was not change significantly. Based on transcriptional response against immune challenge, we could suggest that regulation of TNF-alpha expression may have occurred mainly by LITAF activation rather than NF-kB in disk abalone. The cumulative data from other molluscs and our data with reference to TNF-alpha, LITAF and Rel/NF-kB from disk abalone provide strong evidence that LITAF and NF-kB are independent pathways likely to occur throughout the Phylum mollusca. 2010 Elsevier Ltd. All rights reserved.

Optimal haematocrit in subjects with normal haemoglobin genotype (HbAA), sickle cell trait (HbAS), and homozygous sickle cell disease (HbSS).

PubMed

Bowers, A S; Pepple, D J; Reid, H L

2011-01-01

The determination of an optimal haematocrit (H0) has important clinical implications if such a level can be attained, and more importantly, maintained. This is defined as a haematocrit level, above or below which oxygen delivery is deleteriously affected. This study is designed to determine an optimal haematocrit in normal (AA), sickle cell trait (AS) and sickle cell disease (SS) subjects. Twenty-seven apparently healthy subjects having normal haemoglobin genotype, 24 with sickle cell trait and 42 with homozygous sickle cell disease were recruited into the study. Whole blood viscosity (WBV) was measured by a Wells Brookfield Cone and Plate Viscometer at a shear rate of 230 sec-1. Haematocrit was determined by an AC.Tron Coulter Counter. The optimal haematocrit was calculated as the inverse of a constant, K, which was derived from the haematocrit and viscosity data. Our findings showed that the H0 varied significantly among the 3 haemoglobin genotypes, in the order AA vs SS and AS vs SS. Additionally, the data indicated an increased H0 in subjects with sickle cell trait, suggesting a possible impairment in oxygen delivery in these individuals.

Protein Z G79A polymorphism in Turkish pediatriccerebral infarct patients.

PubMed

Öztürk, Ayşenur; Eğin, Yonca; Deda, Gülhis; Teber, Serap; Akar, Nejat

2008-09-05

Protein Z (PZ) plays an enhancer role in coagulation as an anticoagulant. This is the first study in which G79A polymorphism investigated in Turkish paediatric stroke patients. Ninety-one paediatric stroke patients with cerebral ischemia and 70 control subjects were analyzed for PZ G79A and also FVL, PT mutations. PZ 79 'A' allele in homozygous state was found in five patients (5,5%), while it was found only in one control subject (1,4%) and it was seemed as a risk factor for peadiatric ischemia [OR=3,94 (0,44-35,1)]. When patients and controls who had FVL and PT carriers were excluded, AA genotype carried a risk [OR=3,88 (0,41-36,5)]. Also plasma protein Z levels measured in 21 stroke patients and 52 controls. Plasma protein Z levels were not different between stroke patients (500,95 ngmL-1±158,35) and controls (447,34 ngmL-1±165,97). But the plasma levels of protein Z was decreased in patients with AA genotype. Our data showed that carrying 79 AA genotype could be a genetic risk factor for cerebral infarct in peadiatric patients.

Evaluation of a SNP map of 6q24-27 confirms diabetic nephropathy loci and identifies novel associations type 2 diabetes patients enriched with nephropathy from an African American population

PubMed Central

Leak, Tennille S.; Mychaleckyj, Josyf C.; Smith, Shelly G.; Keene, Keith L.; Gordon, Candace J.; Hicks, Pamela J.; Freedman, Barry I.; Bowden, Donald W.; Sale, Michèle M.

2009-01-01

Previously we performed a genome scan for type 2 diabetes (T2DM) using 638 African-American (AA) affected sibling pairs from 247 families; non-parametric linkage analysis suggested evidence of linkage at 6q24-27 (LOD 2.26). To comprehensively evaluate this region we performed a 2-stage association study by first constructing a SNP map of 754 SNPs selected from HapMap on the basis of linkage disequilibrium (LD) in 300 AAT2DM-ESRD subjects, 311 AA controls, 43 European American controls and 45 Yoruba Nigerian samples (Set 1). Replication analyses were conducted in an independent population of 283 AA T2DM-ESRD subjects and 282 AA controls (Set 2). In addition, we adjusted for the impact of admixture on association results by using ancestry informative markers (AIMs). In Stage 1, 137 (18.2%) SNPs showed nominal evidence of association (P<0.05) in one or more of tests of association: allelic (n=33), dominant (n=36), additive (n=29), or recessive (n=34) genotypic models, and 2- (n=47) and 3-SNP (n=43) haplotypic analyses. These SNPs were selected for follow-up genotyping. Stage 2 analyses confirmed association with a predicted 2-SNP “risk” haplotype in the PARK2 gene. Also, two intergenic SNPs showed consistent genotypic association with T2DM-ESRD: rs12197043 and rs4897081. Combined analysis of all subjects from both stages revealed nominal associations with 17 SNPs within genes; including suggestive associations in ESR1 and PARK2. This study confirms known diabetic nephropathy loci and identifies potentially novel susceptibility variants located within 6q24-27 in AA. PMID:18560894

Influence of Genotype on Structural Atrial Abnormalities and Atrial Fibrillation or Flutter in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy.

PubMed

Bourfiss, Mimount; Te Riele, Anneline S J M; Mast, Thomas P; Cramer, Maarten J; VAN DER Heijden, Jeroen F; VAN Veen, Toon A B; Loh, Peter; Dooijes, Dennis; Hauer, Richard N W; Velthuis, Birgitta K

2016-12-01

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is associated with desmosomal mutations. Although desmosomal disruption affects both ventricles and atria, little is known about atrial involvement in ARVD/C. To describe the extent and clinical significance of structural atrial involvement and atrial arrhythmias (AA) in ARVD/C stratified by genotype. We included 71 patients who met ARVD/C Task Force Criteria and underwent cardiac magnetic resonance (CMR) imaging and molecular genetic analysis. Indexed atrial end-diastolic volume and area-length-ejection-fraction (ALEF) were evaluated on CMR and compared to controls with idiopathic right ventricular outflow tract tachycardia (n = 40). The primary outcome was occurrence of AA (atrial fibrillation or atrial flutter) during follow-up, recorded by 12-lead ECG, Holter monitoring or implantable cardioverter defibrillator (ICD) interrogation. Patients harbored a desmosomal plakophilin-2 (PKP2) (n = 37) or nondesmosomal phospholamban (PLN) (n = 14) mutation. In 20 subjects, no pathogenic mutation was identified. Compared to controls, right atrial (RA) volumes were reduced in PKP2 (P = 0.002) and comparable in PLN (P = 0.441) mutation carriers. In patients with no mutation identified, RA (P = 0.011) and left atrial (P = 0.034) volumes were increased. Bi-atrial ALEF showed no significant difference between the groups. AA were experienced by 27% of patients and occurred equally among PKP2 (30%) and no mutation identified patients (30%), but less among PLN mutation carriers (14%). Genotype influences atrial volume and occurrence of AA in ARVD/C. While the incidence of AA is similar in PKP2 mutation carriers and patients with no mutation identified, PKP2 mutation carriers have significantly smaller atria. This suggests a different arrhythmogenic mechanism. © 2016 Wiley Periodicals, Inc.

Genetic polymorphisms in extracellular superoxide dismutase Leu53Leu, Arg213Gly, and Ala40Thr and susceptibility to type 2 diabetes mellitus.

PubMed

Yang, Y M; Xie, X R; Jin, A L

2016-12-02

The most common type of endocrine disease is type 2 diabetes mellitus (T2DM); genetic factors contribute to the development to T2DM. In this study, we investigated the role of the Leu53Leu, Arg213Gly, and Ala40Thr polymorphisms in extracellular superoxide dismutase (EC-SOD) gene in the development of T2DM in a Chinese population. DNA was extracted from peripheral blood samples obtained from 256 T2DM patients and 324 control subjects recruited from our hospital between January 2013 and March 2015. DNA was genotyped by polymerase chain reaction-restriction fragment length polymorphism. The obtained data was then statistically analyzed. The chi-square test revealed a statistically significant difference in the genotype frequencies of EC-SOD Ala40Thr (χ 2 = 13.26, P = 0.001) between the patients and controls. Unconditional regression analysis indicated that the GA and AA genotypes of EC-SOD Ala40Thr were associated with an increased risk of T2DM compared to the GG genotype {adjusted odds ratio (OR) [95% confidence interval (CI)] = 1.46 (1.01-2.11) and 2.67 (1.48-4.85), respectively}. In the dominant model, the GA+AA genotype of EC-SOD Ala40Thr was correlated with a higher risk of T2DM, in comparison with the GG genotype (OR = 1.64, 95%CI = 1.16-2.33). In the recessive model, AA of EC-SOD Ala40Thr showed a 2.19-fold higher risk of developing T2DM than the GG+GA genotype. In conclusion, people with the Ala40Thr polymorphism in EC-SOD are at a higher risk of developing T2DM; therefore, this may be utilized as a biomarker for early screening of T2DM in a Chinese population.

The association of genetic polymorphisms of hypoxia inducible factor-1 alpha and vascular endothelial growth factor with increased risk of chronic obstructive pulmonary disease: A case-control study.

PubMed

Yu, Zhen-Gang; Wang, Bing-Zhe; Cheng, Zhao-Zhong

2017-09-01

Accumulated data over the years have suggested that hypoxia inducible factor-1 alpha (HIF-1α) and its downstream vascular endothelial growth factor (VEGF) gene may be linked with chronic obstructive pulmonary disease (COPD). This study aims to investigate the association of HIF-1α and VEGF genetic polymorphisms and their correlated risks with COPD. COPD patients (case group) and healthy individuals (control group) were recruited. DNA was extracted to detect HIF-1α and VEGF genetic polymorphisms. Basal lung volume and forced expiratory capacity in 1st second (FEV1)/forced vital capacity (FVC) and FEV 1 /predicted value (pred)% were calculated. Genotype and allele distributions in HIF-1α and VEGF genes were analyzed. Kaplan-Meier curves and logistic regression model were used for analysis of survival and COPD risk factors. Haplotypes for HIF-1α rs11549465 and rs11549467 were analyzed. FEV 1 /FVC and FEV1/pred% in the case group were lower than the control group. Frequencies of HIF-1α rs11549465 CT + TT genotype and T allele, and rs11549467 GA + AA genotype and A allele were higher in the case group than the control group. Patients with rs11549465 CT + TT had higher COPD risk than those with the CC genotype. Patients with rs11549467 GA + AA showed higher COPD risk and lower FEV 1 /FVC and FEV 1 /pred% than those with the GG genotype. Patients with HIF-1α TA haplotype showed higher COPD risk than those with the CG haplotype. Survival rate of patients with HIF-1α rs11549467 GG genotype was higher than those with the GA + AA genotype. HIF-1α rs11549467 polymorphism may be associated with COPD risk. Copyright © 2017. Published by Elsevier Taiwan.

Neurotrophin 3 genotype and emotional adverse effects of osmotic-release oral system methylphenidate (OROS-MPH) in children with attention-deficit/hyperactivity disorder.

PubMed

Park, Subin; Kim, Bung-Nyun; Kim, Jae-Won; Shin, Min-Sup; Cho, Soo-Churl; Kim, Ji-Hoon; Son, Jung-Woo; Shin, Yun-Mi; Chung, Un-Sun; Han, Doug-Hyun

2014-03-01

Neurotrophin 3 (NTF3) has been studied in relation to the pathophysiology of attention-deficit/hyperactivity disorder (ADHD) and mood disorders as well as psychostimulant action. We hypothesized that the risk of an emotional side effect to methylphenidate (MPH) treatment may be associated with NTF3 genotypes. Ninety-six medication-naïve children with ADHD (mean age 8.70, standard deviation 1.41 years, 79 males) were genotyped and treated with MPH. At baseline, which was prior to MPH treatment, and after two weeks of medication, investigators asked children and their parents or caregivers about adverse events using a symptom rating scale. ADHD subjects with the A/A genotype at the NTF3 rs6332 polymorphism showed the highest 'Emotionality' and 'Over-focus/euphoria' factor scores, followed by those with the G/A genotype and those with the G/G genotype (p=0.042 and p=0.045, respectively). ADHD subjects with the A/A genotype at the NTF3 rs6332 polymorphism showed the highest 'Proneness to crying' and 'Nail biting' item scores, followed by those with the G/A genotype and those with the G/G genotype (p=0.047 and p=0.017, respectively). These data provide preliminary evidence that genetic variation in the NTF3 gene is related to susceptibility to emotional side effects in response to MPH treatment in Korean children with ADHD.

Impact of diabetes-related gene polymorphisms on the clinical characteristics of type 2 diabetes Chinese Han population.

PubMed

Li, Jing; Wei, Jiachen; Xu, Pengcheng; Yan, Mengdan; Li, Jingjie; Chen, Zhengshuai; Jin, Tianbo

2016-12-20

We investigated the correlation between type 2 diabetes (T2D)-related genes and the clinical characteristics of T2D in the Chinese Han population. Our study included 319 patients and 387 controls. Age, gender, clinical features, medications intake and biochemical blood profiles were analyzed. Genotyping was performed on a total of 18 single nucleotide polymorphisms previously reported to be associated with T2D. Our analyses revealed that the CT genotype of ARHGAP22 rs4838605 is associated with T2D risk. Upon analyzing the subjects' clinical characteristics, we found that for rs2811893, the TT genotype correlated with high creatinine levels, while the AA genotype of rs17045754 and the TT genotype of rs4838605 correlated with elevated triglyceride levels. In addition, the AA genotype of rs17376456 and the TT genotype of rs6214 (p = 0.006) correlated with elevated hemoglobin A1c levels. Lastly, those carrying the TT genotype of rs7772697 and the CA genotype of rs3918227 exhibited higher mean body mass index and Cystatin C than controls. Our results showing that the ARHGAP22 gene is associated with an increased risk of T2D, and that seven SNPs in MYSM1, PLXDC2, ARHGAP22 and HS6ST3 promote T2D progression and could help predict the clinical course of T2D in patients at risk.

Galactose-1-phospate uridyltransferase

MedlinePlus

... normal diets, most galactose comes from the breakdown ( metabolism ) of lactose, which is found in milk and ... Elsevier; 2013:550. Zinn AB. Inborn errors of metabolism. In: Martin RJ, Fanaroff AA, Walsh MC, eds. ...

Religion priming and an oxytocin receptor gene (OXTR) polymorphism interact to affect self-control in a social context.

PubMed

Sasaki, Joni Y; Mojaverian, Taraneh; Kim, Heejung S

2015-02-01

Using a genetic moderation approach, this study examines how an experimental prime of religion impacts self-control in a social context, and whether this effect differs depending on the genotype of an oxytocin receptor gene (OXTR) polymorphism (rs53576). People with different genotypes of OXTR seem to have different genetic orientations toward sociality, which may have consequences for the way they respond to religious cues in the environment. In order to determine whether the influence of religion priming on self-control is socially motivated, we examine whether this effect is stronger for people who have OXTR genotypes that should be linked to greater rather than less social sensitivity (i.e., GG vs. AA/AG genotypes). The results showed that experimentally priming religion increased self-control behaviors for people with GG genotypes more so than people with AA/AG genotypes. Furthermore, this Gene × Religion interaction emerged in a social context, when people were interacting face to face with another person. This research integrates genetic moderation and social psychological approaches to address a novel question about religion's influence on self-control behavior, which has implications for coping with distress and psychopathology. These findings also highlight the importance of the social context for understanding genetic moderation of psychological effects.

Significance of genetic variants in DLC1 and their association with hepatocellular carcinoma

PubMed Central

XIE, CHENG-RONG; SUN, HONG-GUANG; SUN, YU; ZHAO, WEN-XIU; ZHANG, SHENG; WANG, XIAO-MIN; YIN, ZHEN-YU

2015-01-01

DLC1 has been shown to be downregulated or absent in hepatocellular carcinoma (HCC) and is associated with tumorigenesis and development. However, only a small number of studies have focused on genetic variations of DLC1. The present study performed exon sequencing for the DLC1 gene in HCC tissue samples from 105 patients to identify functional genetic variation of DLC1 and its association with HCC susceptibility, clinicopathological features and prognosis. A novel missense mutation and four non-synonymous single nucleotide polymorphisms (SNPs; rs3816748, rs11203495, rs3816747 and rs532841) were identified. A significant correlation of rs3816747 polymorphisms with HCC susceptibility was identified. Compared to individuals with the GG genotype of rs3816747, those with the GA (odds ratio (OR)=0.486; P=0.037) or GA+AA genotype (OR=0.51; P=0.039) were associated with a significantly decreased HCC risk. Furthermore, patients with the GC+CC genotype of rs3816748, the TC+CC genotype of rs11203495 or the GA+AA genotype of rs3816747 had small-sized tumors compared with those carrying the wild-type genotype. No significant association of DLC1 SNPs with the patients' prognosis was found. These results indicated that genetic variations in the DLC1 gene may confer a risk for HCC. PMID:26095787

Screening white spot syndrome virus (WSSV)-resistant molecular markers from Fenneropenaeus chinensis

NASA Astrophysics Data System (ADS)

Wu, Yingying; Meng, Xianhong; Kong, Jie; Luan, Sheng; Luo, Kun; Wang, Qingyin; Zheng, Yongyun

2017-02-01

White spot syndrome virus (WSSV)-resistant molecular markers were screened from the selectively bred new variety `Huanghai No. 2' of Fenneropenaeus chinensis using unlabeled-probe high-resolution melting (HRM) technique. After the artificial infection with WSSV, the first 96 dead shrimps and the last 96 surviving shrimps were collected, representing WSSV-susceptible and -resistant populations, respectively. The genotypes at well-developed 39 single nucleotide polymorphisms (SNPs) loci were obtained. As revealed in the Chi-square test, 3 SNPs, genotype A/A of contig C364-89AT, genotype A/A of C2635-527CA and genotype C/T of contig C12355-592CT, were positively correlated with disease-resistance traits. Other 2 SNPs, genotype G/G of contig C283-145AG and genotype C/C of contig C12355-592CT, were negatively correlated. Moreover, analysis with BlastX program for disease-resistant SNPs indicated that 3 contigs, Contig283, Contig364 and Contig12355, matched to the functional genes of effector caspase of Penaeus monodon, peptide transporter family 1-like protein, and 40S ribosomal protein S2 of Perca flavescens with high sequence similarity. The results will be helpful to provide theoretical and technical supports for molecular marker-assisted selective breeding of F. chinensis.

The impact of the catechol-O-methyltransferase genotype on vascular function and blood pressure after acute green tea ingestion.

PubMed

Miller, Rosalind J; Jackson, Kim G; Dadd, Tony; Mayes, Andrew E; Brown, A Louise; Lovegrove, Julie A; Minihane, Anne M

2012-06-01

Evidence for the benefits of green tea catechins on vascular function is inconsistent, with genotype potentially contributing to the heterogeneity in response. Here, the impact of the catechol-O-methyltransferase (COMT) genotype on vascular function and blood pressure (BP) after green tea extract ingestion are reported. Fifty subjects (n = 25 of the proposed low-activity [AA] and of the high-activity [GG] COMT rs4680 genotype), completed a randomized, double-blind, crossover study. Peripheral arterial tonometry, digital volume pulse (DVP), and BP were assessed at baseline and 90 min after 1.06 g of green tea extract or placebo. A 5.5 h and subsequent 18.5 h urine collection was performed to assess green tea catechin excretion. A genotype × treatment interaction was observed for DVP reflection index (p = 0.014), with green tea extract in the AA COMT group attenuating the increase observed with placebo. A tendency for a greater increase in diastolic BP was evident at 90 min after the green tea extract compared to placebo (p = 0.07). A genotypic effect was observed for urinary methylated epigallocatechin during the first 5.5 h, with the GG COMT group demonstrating a greater concentration (p = 0.049). Differences in small vessel tone according to COMT genotype were evident after acute green tea extract. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Human Monoclonal Antibodies to a Novel Cluster of Conformational Epitopes on HCV E2 with Resistance to Neutralization Escape in a Genotype 2a Isolate

PubMed Central

Keck, Zhen-yong; Xia, Jinming; Wang, Yong; Wang, Wenyan; Krey, Thomas; Prentoe, Jannick; Carlsen, Thomas; Li, Angela Ying-Jian; Patel, Arvind H.; Lemon, Stanley M.; Bukh, Jens; Rey, Felix A.; Foung, Steven K. H.

2012-01-01

The majority of broadly neutralizing antibodies to hepatitis C virus (HCV) are against conformational epitopes on the E2 glycoprotein. Many of them recognize overlapping epitopes in a cluster, designated as antigenic domain B, that contains residues G530 and D535. To gain information on other regions that will be relevant for vaccine design, we employed yeast surface display of antibodies that bound to genotype 1a H77C E2 mutant proteins containing a substitution either at Y632A (to avoid selecting non-neutralizing antibodies) or D535A. A panel of nine human monoclonal antibodies (HMAbs) was isolated and designated as HC-84-related antibodies. Each HMAb neutralized cell culture infectious HCV (HCVcc) with genotypes 1–6 envelope proteins with varying profiles, and each inhibited E2 binding to the viral receptor CD81. Five of these antibodies neutralized representative genotypes 1–6 HCVcc. Epitope mapping identified a cluster of overlapping epitopes that included nine contact residues in two E2 regions encompassing aa418–446 and aa611–616. Effect on virus entry was measured using H77C HCV retroviral pseudoparticles, HCVpp, bearing an alanine substitution at each of the contact residues. Seven of ten mutant HCVpp showed over 90% reduction compared to wild-type HCVpp and two others showed approximately 80% reduction. Interestingly, four of these antibodies bound to a linear E2 synthetic peptide encompassing aa434–446. This region on E2 has been proposed to elicit non-neutralizing antibodies in humans that interfere with neutralizing antibodies directed at an adjacent E2 region from aa410–425. The isolation of four HC-84 HMAbs binding to the peptide, aa434–446, proves that some antibodies to this region are to highly conserved epitopes mediating broad virus neutralization. Indeed, when HCVcc were passaged in the presence of each of these antibodies, virus escape was not observed. Thus, the cluster of HC-84 epitopes, designated as antigenic domain D, is relevant for vaccine design for this highly diverse virus. PMID:22511875

Association of methylenetetrahytrofolate reductase (MTHFR) C677T and A1298C polymorphisms with the susceptibility of childhood acute lymphoblastic leukaemia (ALL) in Chinese population.

PubMed

Li, Xiaolei; Liao, Qingchuan; Zhang, Shunguo; Chen, Minling

2014-01-29

The aim of this study was to investigate the relationship between the polymorphisms of the methylenetetrahytrofolate reductase (MTHFR) gene and susceptibility to childhood acute lymphoblastic leukemia (ALL). A case-control study was conducted among 98 children with ALL and 93 age- and sex- matched non-ALL controls. Genotyping of MTHFR C677T and A1298C polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The odds ratios (ORs) of MTHFR genotypes were used to assess the associations of these polymorphisms with childhood ALL susceptibility. No significant differences were observed for frequencies of the 677CC, 677CT and 677TT genotypes between patients and controls. Frequencies of the 1298AA, 1298 AC and 1298CC genotypes between the two groups were significantly different. The risk of ALL with the 1298C allele carriers (AC + CC) was elevated by 1.1 times compared with the AA genotype [OR = 2.100; 95% CI (1.149; 3.837); P = 0.015]. The MTHFR A1298C polymorphism is associated with susceptibility to childhood ALL in the Chinese population.

Time Domain Aperture Antenna Study. Volume 1

DTIC Science & Technology

1974-10-01

IS. KF.Y WORDS (Vo, wo em e•,.’*I aIdv ft # .ce.-y ws4 tdanti, &Ow W•Ai nw* Ab ) Antennas Tranalent Aperture Radiation t.•’t. hiNATIONAL TECHNICAL...aL3 Cora 4 la V%") AA C05 (11c) Substituting Eq. (11) into (8), and using Eq. (5) gives - Ab . c ~ ve Gv (12A) (12B The bracketed terms in Eq. (12) may...experimental data on an ab :;olute basis in thi.; report. S57 - CHAPTER 3 TRANSIENT RADIATION FROM A PARABOLOID 3.1 INTRODUC T ION This chapter is intended to

Serum Amyloid A Protein Concentration in Blood is Influenced by Genetic Differences in the Cheetah (Acinonyx jubatus)

PubMed Central

Schmidt-Küntzel, Anne; Terio, Karen A; Marker, Laurie L; Crosier, Adrienne E

2016-01-01

Abstract Systemic amyloid A (AA) amyloidosis is a major cause of morbidity and mortality among captive cheetahs. The self-aggregating AA protein responsible for this disease is a byproduct of serum amyloid A (SAA) protein degradation. Transcriptional induction of the SAA1 gene is dependent on both C/EBPβ and NF-κB cis-acting elements within the promoter region. In cheetahs, 2 alleles exist for a single guanine nucleotide deletion in the putative NF-κB binding site. In this study, a novel genotyping assay was developed to screen for the alleles. The results show that the SAA1A−97delG allele is associated with decreased SAA protein concentrations in the serum of captive cheetahs (n = 58), suggesting genetic differences at this locus may be affecting AA amyloidosis prevalence. However, there was no significant difference in the frequency of the SAA1A−97delG allele between individuals confirmed AA amyloidosis positive versus AA amyloidosis negative at the time of necropsy (n = 48). Thus, even though there is evidence that having more copies of the SAA1A−97delG allele results in a potentially protective decrease in serum concentrations of SAA protein in captive cheetahs, genotype is not associated with this disease within the North American population. These results suggest that other factors are playing a more significant role in the pathogenesis of AA amyloidosis among captive cheetahs. PMID:26585380

Correlations of EGF G1380A, bFGF C754G and VEGF T460C polymorphisms with malignant melanoma susceptibility and prognosis: A case-control study.

PubMed

Wang, Xin-Hua; Long, Zi-Wen

2017-06-20

This case-control study aims to investigate the correlations of EGF G1380A, bFGF C754G and VEGF T460C polymorphisms with the susceptibility and prognosis of malignant melanoma. A total of 153 patients with multiple primary melanomas were collected as the case group and another 170 healthy individuals were selected as the control group. ELISA and PCR-RFLP were performed to test the serum level of VEGF and to analyze the genotype as well as allele frequencies of VEGF T460C, EGF G1380A, and bFGF C754G, respectively. The patients were assigned into complete remission (CR), partial remission (PR) and non-remission groups after treatment. HE and CD34 staining were conducted in tissue samples of CR and PR patients. Event-free survival (EFS) and overall survival (OS) were measured. AA genotype of EGF G1380A and GG genotype of bFGF C754G had higher frequency distribution in the case group than the control group. Patients with AA genotype of EGF G1380 and GG genotype of bFGF C754G had an elevated VEGF level in comparison to other genotypes. Patients with GA+GG genotypes of EGF G1380A and CG+CC genotypes of bFGF C754G had higher EFS and OS than those with AA genotype and those with GG genotype, respectively. According to the haplotype analysis, the case group had a notably higher frequency of TAG and CAG along with while lower frequency of TGG and CGC compared with the control group. Logistic regression analysis revealed that the polymorphisms of EGF G1380A and bFGF C754G as well as the haploid TAG increased the susceptibility of malignant melanoma. The results indicated that EGF G1380A and bFGF C754G gene polymorphisms were associated with the susceptibility and prognosis of malignant melanoma, and that the polymorphisms of EGF G1380A and bFGF C754G as well as the haploid TAG increased the susceptibility of malignant melanoma. Copyright © 2017 Elsevier B.V. All rights reserved.

Age-specific effects of estrogen receptors' polymorphisms on the bone traits in healthy fertile women: the BONTURNO study

PubMed Central

Massart, Francesco; Marini, Francesca; Bianchi, Gerolamo; Minisola, Salvatore; Luisetto, Giovanni; Pirazzoli, Antonella; Salvi, Sara; Micheli, Dino; Masi, Laura; Brandi, Maria Luisa

2009-01-01

Background Skeletal characteristics such as height (Ht), bone mineral density (BMD) or bone turnover markers are strongly inherited. Common variants in the genes encoding for estrogen receptor alpha (ESR1) and beta (ESR2) are proposed as candidates for influencing bone phenotypes at the population level. Methods We studied 641 healthy premenopausal women aged 20–50 years (yrs) participating into the BONTURNO study. Exclusion criteria were irregular cyclic menses, low trauma fracture, metabolic bone or chronic diseases. Serum C-telopeptide of type I collagen (CTX), osteocalcin (OC), and N-terminal propeptide of type I procollagen (P1NP) were measured in all enrolled subjects, who underwent to lumbar spine (LS), total hip (TH) and femoral neck (FN) BMD evaluation by DXA. Five hundred seventy Caucasian women were genotyped for ESR1 rs2234693 and rs9340799 and ESR2 rs4986938 polymorphisms. Results Although no genotype differences were found in body parameters, subjects with combined ESR1 CCGG plus ESR2 AA-AG genotype were taller than those with opposite genotype (P = 0.044). Moreover, ESR1 rs2234693 genotypes correlated with family history of osteoporosis (FHO) and hip fracture (FHF) (P < 0.01), while ESR2 AA-AC genotypes were strongly associated with FHF (OR 2.387, 95% CI 1.432–3.977; P < 0.001). When clustered by age, 20–30 yrs old subjects, having at least one ESR1 rs2234693 C allele presented lower LS- (P = 0.008) and TH-BMD (P = 0.047) than TT genotypes. In 41–50 yrs age, lower FN-BMD was associated with ESR2 AA (P = 0.0180) subjects than in those with the opposite genotype. ESR1 rs2234693 and rs9340799 and ESR2 rs4986938 polymorphisms did not correlate with age-adjusted values of OC, CTX and P1NP. Conclusion These findings support the presence of age-specific effects of ESR1 and ESR2 polymorphisms on various skeletal traits in healthy fertile women. PMID:19386104

PAI-1 gain-of-function genotype, factors increasing PAI-1 levels, and airway obstruction: The GALA II Cohort.

PubMed

Sherenian, M G; Cho, S H; Levin, A; Min, J-Y; Oh, S S; Hu, D; Galanter, J; Sen, S; Huntsman, S; Eng, C; Rodriguez-Santana, J R; Serebrisky, D; Avila, P C; Kalhan, R; Smith, L J; Borrell, L N; Seibold, M A; Keoki Williams, L; Burchard, E G; Kumar, R

2017-09-01

PAI-1 gain-of-function variants promote airway fibrosis and are associated with asthma and with worse lung function in subjects with asthma. We sought to determine whether the association of a gain-of-function polymorphism in plasminogen activator inhibitor-1 (PAI-1) with airway obstruction is modified by asthma status, and whether any genotype effect persists after accounting for common exposures that increase PAI-1 level. We studied 2070 Latino children (8-21y) with genotypic and pulmonary function data from the GALA II cohort. We estimated the relationship of the PAI-1 risk allele with FEV1/FVC by multivariate linear regression, stratified by asthma status. We examined the association of the polymorphism with asthma and airway obstruction within asthmatics via multivariate logistic regression. We replicated associations in the SAPPHIRE cohort of African Americans (n=1056). Secondary analysis included the effect of the at-risk polymorphism on postbronchodilator lung function. There was an interaction between asthma status and the PAI-1 polymorphism on FEV 1 /FVC (P=.03). The gain-of-function variants, genotypes (AA/AG), were associated with lower FEV 1 /FVC in subjects with asthma (β=-1.25, CI: -2.14,-0.35, P=.006), but not in controls. Subjects with asthma and the AA/AG genotypes had a 5% decrease in FEV 1 /FVC (P<.001). In asthmatics, the risk genotype (AA/AG) was associated with a 39% increase in risk of clinically relevant airway obstruction (OR=1.39, CI: 1.01, 1.92, P=.04). These associations persisted after exclusion of factors that increase PAI-1 including tobacco exposure and obesity. The decrease in the FEV 1 /FVC ratio associated with the risk genotype was modified by asthma status. The genotype increased the odds of airway obstruction by 75% within asthmatics only. As exposures known to increase PAI-1 levels did not mitigate this association, PAI-1 may contribute to airway obstruction in the context of chronic asthmatic airway inflammation. © 2017 John Wiley & Sons Ltd.

Genetic association between the dopamine D1-receptor gene and paranoid schizophrenia in a northern Han Chinese population.

PubMed

Yao, Jun; Ding, Mei; Xing, Jiaxin; Xuan, Jinfeng; Pang, Hao; Pan, Yuqing; Wang, Baojie

2014-01-01

Dysregulation of dopaminergic neurotransmission at the D1 receptor in the prefrontal cortex has been implicated in the pathogenesis of schizophrenia. Genetic polymorphisms of the dopamine D1-receptor gene have a plausible role in modulating the risk of schizophrenia. To determine the role of DRD1 genetic polymorphisms as a risk factor for schizophrenia, we undertook a case-control study to look for an association between the DRD1 gene and schizophrenia. We genotyped eleven single-nucleotide polymorphisms within the DRD1 gene by deoxyribonucleic acid sequencing involving 173 paranoid schizophrenia patients and 213 unrelated healthy individuals. Statistical analysis was performed to identify the difference of genotype, allele, or haplotype distribution between cases and controls. A significantly lower risk of paranoid schizophrenia was associated with the AG + GG genotype of rs5326 and the AG + GG genotype of rs4532 compared to the AA genotype and the AA genotype, respectively. Distribution of haplotypes was no different between controls and paranoid schizophrenia patients. In the males, the genotype distribution of rs5326 was statistically different between cases and controls. In the females, the genotype distribution of rs4532 was statistically different between cases and controls. However, the aforementioned statistical significances were lost after Bonferroni correction. It is unlikely that DRD1 accounts for a substantial proportion of the genetic risk for schizophrenia. As an important dopaminergic gene, DRD1 may contribute to schizophrenia by interacting with other genes, and further relevant studies are warranted.

The polymorphism -863C/A in tumour necrosis factor-alpha gene contributes an independent association to gout.

PubMed

Chang, S-J; Tsai, P-C; Chen, C-J; Lai, H-M; Ko, Y-C

2007-11-01

To investigate the associations between polymorphisms in the promoter of the tumour necrosis factor-alpha (TNF-alpha) gene and gout. The polymorphisms -308G/A and -863C/A in the TNF-alpha gene were determined in 106 gout patients and 159 healthy controls among male Taiwanese using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. The biochemical markers, including Glutamic-oxaloacetic transaminase (GOT), Glutamic-pyruvic transaminase (GPT), uric acid, creatinine, total cholesterol (TC), triglycerides (TG), body mass index (BMI) and hypertension, as well as alcohol consumption were measured. The gout patients had 9.43% (10/106) with genotype AA at polymorphism -863C/A showing a significantly higher fraction than controls (0.63%; 1/159, P < 0.001). The crude results also showed that the gout patients had significantly higher portions of abnormal GOT, GPT, creatinine, TC, TG, alcohol consumption, hypertension and hyperuricaemia than controls (P < 0.05), but the -308G/A, BMI and genotype CA at -863C/A did not show the same significant difference (P > 0.05). After adjustment by a stepwise logistic regression method, the hyperuricaemia, creatinine, GPT, TG and alcohol consumption as well as genotype AA at polymorphism -863C/A were found to be significantly associated with gout. The genotype AA at polymorphism -863C/A in a recessive model showed a significant association with developing gout independent of hyperuricaemia, abnormal creatinine, higher TG, GPT and alcohol consumption.

Racial Differences in CYP3A4 Genotype and Survival Among Men Treated on Radiation Therapy Oncology Group (RTOG) 9202: A Phase III Randomized Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roach, Mack; Silvio, Michelle de; Rebbick, Timothy

2007-09-01

Purpose: Inherited genotypes may explain the inferior outcomes of African American (AA) men with prostate cancer. To understand how variation in CYP3A4 correlated with outcomes, a retrospective examination of the CYP3A4*1B genotype was performed on men treated with Radiation Therapy Oncology Group (RTOG) 92-02. Methods and Materials: From 1,514 cases, we evaluated 56 (28.4%) of 197 AA and 54 (4.3%) of 1,274 European American (EA) patients. All patients received goserelin and flutamide for 2 months before and during RT (STAD-RT) {+-} 24 months of goserelin (long-term androgen deprivation plus radiation [LTAD-RT]). Events studied included overall survival and biochemical progression usingmore » American Society for Therapeutic Radiology and Oncology consensus guidelines. Results: There were no differences in outcome in patients in with or without CYP3A4 data. There was an association between race and CYP3A4 polymorphisms with 75% of EAs having the Wild Type compared to only 25% of AA men (p <0.0001). There was no association between CYP3A4 classification or race and survival or progression. Conclusions: The samples analyzed support previously reported observations about the distribution of CYP3A4*1B genotype by race, but race was not associated with poorer outcome. However, patient numbers were limited, and selection bias cannot be completely ruled out.« less

Topological Entropy Measure of Artificial Grammar Complexity for Use in Designing Experiments on Human Performance in Intelligence, Surveillance, and Reconnaissance (ISR) Tasks

DTIC Science & Technology

2015-04-02

grammar may be stated as AA 6→ AA, so not form AAA xB 6→ BB, so not form xBB xS 6→ SS, so not form xSS SA 6→ AB, so not form SAB BA 6→ AS, so not form BAS... 350 . Dienes, Z., & Scott, R. (2005). Measuring Unconscious Knowledge: Distinguishing Structural Knowledge and Judgment Knowledge. Psychological

Resting-State Brain and the FTO Obesity Risk Allele: Default Mode, Sensorimotor, and Salience Network Connectivity Underlying Different Somatosensory Integration and Reward Processing between Genotypes.

PubMed

Olivo, Gaia; Wiemerslage, Lyle; Nilsson, Emil K; Solstrand Dahlberg, Linda; Larsen, Anna L; Olaya Búcaro, Marcela; Gustafsson, Veronica P; Titova, Olga E; Bandstein, Marcus; Larsson, Elna-Marie; Benedict, Christian; Brooks, Samantha J; Schiöth, Helgi B

2016-01-01

Single-nucleotide polymorphisms (SNPs) of the fat mass and obesity associated (FTO) gene are linked to obesity, but how these SNPs influence resting-state neural activation is unknown. Few brain-imaging studies have investigated the influence of obesity-related SNPs on neural activity, and no study has investigated resting-state connectivity patterns. We tested connectivity within three, main resting-state networks: default mode (DMN), sensorimotor (SMN), and salience network (SN) in 30 male participants, grouped based on genotype for the rs9939609 FTO SNP, as well as punishment and reward sensitivity measured by the Behavioral Inhibition (BIS) and Behavioral Activation System (BAS) questionnaires. Because obesity is associated with anomalies in both systems, we calculated a BIS/BAS ratio (BBr) accounting for features of both scores. A prominence of BIS over BAS (higher BBr) resulted in increased connectivity in frontal and paralimbic regions. These alterations were more evident in the obesity-associated AA genotype, where a high BBr was also associated with increased SN connectivity in dopaminergic circuitries, and in a subnetwork involved in somatosensory integration regarding food. Participants with AA genotype and high BBr, compared to corresponding participants in the TT genotype, also showed greater DMN connectivity in regions involved in the processing of food cues, and in the SMN for regions involved in visceral perception and reward-based learning. These findings suggest that neural connectivity patterns influence the sensitivity toward punishment and reward more closely in the AA carriers, predisposing them to developing obesity. Our work explains a complex interaction between genetics, neural patterns, and behavioral measures in determining the risk for obesity and may help develop individually-tailored strategies for obesity prevention.

Resting-State Brain and the FTO Obesity Risk Allele: Default Mode, Sensorimotor, and Salience Network Connectivity Underlying Different Somatosensory Integration and Reward Processing between Genotypes

PubMed Central

Olivo, Gaia; Wiemerslage, Lyle; Nilsson, Emil K.; Solstrand Dahlberg, Linda; Larsen, Anna L.; Olaya Búcaro, Marcela; Gustafsson, Veronica P.; Titova, Olga E.; Bandstein, Marcus; Larsson, Elna-Marie; Benedict, Christian; Brooks, Samantha J.; Schiöth, Helgi B.

2016-01-01

Single-nucleotide polymorphisms (SNPs) of the fat mass and obesity associated (FTO) gene are linked to obesity, but how these SNPs influence resting-state neural activation is unknown. Few brain-imaging studies have investigated the influence of obesity-related SNPs on neural activity, and no study has investigated resting-state connectivity patterns. We tested connectivity within three, main resting-state networks: default mode (DMN), sensorimotor (SMN), and salience network (SN) in 30 male participants, grouped based on genotype for the rs9939609 FTO SNP, as well as punishment and reward sensitivity measured by the Behavioral Inhibition (BIS) and Behavioral Activation System (BAS) questionnaires. Because obesity is associated with anomalies in both systems, we calculated a BIS/BAS ratio (BBr) accounting for features of both scores. A prominence of BIS over BAS (higher BBr) resulted in increased connectivity in frontal and paralimbic regions. These alterations were more evident in the obesity-associated AA genotype, where a high BBr was also associated with increased SN connectivity in dopaminergic circuitries, and in a subnetwork involved in somatosensory integration regarding food. Participants with AA genotype and high BBr, compared to corresponding participants in the TT genotype, also showed greater DMN connectivity in regions involved in the processing of food cues, and in the SMN for regions involved in visceral perception and reward-based learning. These findings suggest that neural connectivity patterns influence the sensitivity toward punishment and reward more closely in the AA carriers, predisposing them to developing obesity. Our work explains a complex interaction between genetics, neural patterns, and behavioral measures in determining the risk for obesity and may help develop individually-tailored strategies for obesity prevention. PMID:26924971

Polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) are associated with susceptibility to adult acute myeloid leukemia in a Chinese population.

PubMed

Huang, Lulu; Deng, Donghong; Peng, Zhigang; Ye, Fanghui; Xiao, Qiang; Zhang, Bing; Ye, Bingbing; Mo, Zengnan; Yang, Xiaobo; Liu, Zhenfang

2015-06-01

Methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme in the metabolism of folate. Since acute myeloid leukemia (AML) is characterized by rapidly proliferating tissues that have a high requirement for DNA synthesis, it is possible that the presence of MTHFR polymorphisms could be linked to the multifactorial process of AML development. We evaluated the role of MTHFR C677T and A1298C polymorphisms in a case-control study comprising 98 AML patients and 2016 healthy controls in a Southern Chinese population. We further conducted a sub-study restricted to individuals who neither smoked nor drank alcohol (70 AML patients and 160 healthy controls). MTHFR polymorphisms in the patient and control groups were evaluated by SNaP shot genotype techniques and Illumina BeadChip, respectively. Logistic regression was used to assess the adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). The MTHFR 1298AC genotype and the 677CC/1298AC haplotype were significantly associated with a decreased risk of AML compared with the AA genotype and 677CC/1298AA haplotype (OR=0.60, 95% CI: 0.38-0.95, P=0.03; OR=0.49, 95% CI: 0.27-0.90, P=0.02, respectively). In addition, the 677TT genotype was significantly associated with an increased risk of AML compared with the AA genotype only in non-smokers and non-drinkers (OR=4.78; 95% CI=1.38-16.61, P=0.01). The results might suggest that MTHFR polymorphisms are significantly associated with AML risk. In addition, the role of MTHFR genetic susceptibility could be greater among non-smokers and non-drinkers. Copyright © 2015 Elsevier Ltd. All rights reserved.

Influence of the Temperature and the Genotype of the HSP90AA1 Gene over Sperm Chromatin Stability in Manchega Rams

PubMed Central

Ramón, Manuel; Salces-Ortiz, Judit; González, Carmen; Pérez-Guzmán, M. Dolores; Garde, J. Julián; García-Álvarez, Olga; Maroto-Morales, Alejandro; Calvo, Jorge H.; Serrano, M. Magdalena

2014-01-01

The present study addresses the effect of heat stress on males' reproduction ability. For that, we have evaluated the sperm DNA fragmentation (DFI) by SCSA of ejaculates incubated at 37°C during 0, 24 and 48 hours after its collection, as a way to mimic the temperature circumstances to which spermatozoa will be subject to in the ewe uterus. The effects of temperature and temperature-humidity index (THI) from day 60 prior collection to the date of semen collection on DFI were examined. To better understand the causes determining the sensitivity of spermatozoa to heat, this study was conducted in 60 males with alternative genotypes for the SNP G/C−660 of the HSP90AA1 promoter, which encode for the Hsp90α protein. The Hsp90α protein predominates in the brain and testis, and its role in spermatogenesis has been described in several species. Ridge regression analyses showed that days 29 to 35 and 7 to 14 before sperm collection (bsc) were the most critical regarding the effect of heat stress over DFI values. Mixed model analyses revealed that DFI increases over a threshold of 30°C for maximum temperature and 22 for THI at days 29 to 35 and 7 to 14 bsc only in animals carrying the GG−660 genotype. The period 29–35 bsc coincide with the meiosis I process for which the effect of the Hsp90α has been described in mice. The period 7–14 bsc may correspond with later stages of the meiosis II and early stages of epididymal maturation in which the replacement of histones by protamines occurs. Because of GG−660 genotype has been associated to lower levels of HSP90AA1 expression, suboptimal amounts of HSP90AA1 mRNA in GG−660 animals under heat stress conditions make spermatozoa DNA more susceptible to be fragmented. Thus, selecting against the GG−660 genotype could decrease the DNA fragmentation and spermatozoa thermal susceptibility in the heat season, and its putative subsequent fertility gains. PMID:24465903

Clinical study on gastric cancer susceptibility genes IL-10-1082 and TNF-α.

PubMed

Yu, T; Lu, Q; Ou, X L; Cao, D Z; Yu, Q

2014-12-19

TNF 308 gene polymorphism and IL-10 polymorphism provided evidence in diagnosing some types of cancer. We aimed to explore the relation of gene polymorphism with gastric cancer. A total of 360 cases of gastric cancer patients were included in the study. The genotypes GG, GA, and AA of the interleukin-10-1082 gene (IL-10-1082) and the tumor necrosis factor-alpha gene (TNF-α) 308 polymorphism were examined by chromogenic detection. Three hundred healthy individuals' gene as control group were also examined. The GA 308 genotype of TNF-α differed significantly between the control group and the gastric cancer group (X(2) = 9.32, P < 0.05). Genotype frequencies of A/A (17.2%), A/G (26.2%), and G/G (9.1%) of the IL-10-1082 gene polymorphism in the gastric cancer group differed significantly compared to those of the control group (X(2) = 20.32, P < 0.05). The IL-10-1082 gene and the GA 308 genotype of the TNF-α gene were found to be susceptibility genes for gastric cancer.

[Association of single nucleotide polymorphism of methylenetetrahydrofolate reductase gene with susceptibility to acute leukemia].

PubMed

Zheng, Miao-miao; Yue, Li-jie; Zhang, Hong-hong; Yang, Chun-lan; Xie, Cai

2013-08-01

To assess whether polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene is associated with susceptibility to acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) in Chinese Han children. The study has included 87 patients with ALL, 22 patients with AML and 120 healthy controls. All subjects were analyzed with reverse transcriptase-polymerase chain reaction-denaturing gradient gel electrophoresis and sequencing. A 677CT genotype of the MTHFR gene was associated with decreased risk of ALL (OR=0.23, 95%CI: 0.07-0.79). However, MTHFR A1298C genotypes were not associated with the risk of either disease. 677TT/1298AA and 677CC/1298AC genotypes were associated with increased risk of ALL(OR=3.78, 95% CI: 1.38-10.40; OR=3.17, 95% CI: 1.18-8.53, respectively), whereas the genotype 677CT/1298AA was associated with susceptibility to AML (OR=0.23, 95% CI: 0.06-0.97). Our data suggested that C677T polymorphism of MTHFR gene may increase the risk of childhood AML.

Comparative haematological parameters of HbAA and HbAS genotype children infected with Plasmodium falciparum malaria in Yemen.

PubMed

Albiti, Anisa H; Nsiah, Kwabena

2014-04-01

Sickle haemoglobin (HbS) is known to offer considerable protection against falciparum malaria. However, the mechanism of protection is not yet completely understood. In this study, we investigate how the presence of the sickle cell trait affects the haematological profile of AS persons with malaria, in comparison with similarly infected persons with HbAA. This study is based on the hypothesis that the sickle cell trait plays a protective role against malaria. Children from an endemic malaria transmission area in Yemen were enrolled in this study. Hematological parameters were estimated using manual methods, the percentage of parasite density on stained thin smear was calculated, haemoglobin genotypes were determined on paper electrophoresis, ferritin was measured using enzyme-linked immunosorbent assay, serum iron and TIBC were assayed using spectrophotometer, transferrin saturation index was calculated by dividing serum iron by TIBC and expressing the result as a percentage. Haematological parameters were compared in HbAA- and HbAS-infected children. Falciparum malaria parasitaemia was confirmed in the blood smears of 62 children, 44 (55.7%) of AA and 18 (37.5%) AS, so there was higher prevalence in HbAA children (P = 0.047). Parasite density was lower in HbAS- than HbAA-infected children (P = 0.003). Anaemia was prominent in malaria-infected children, with high proportions of moderate and severe forms in HbAA (P = 0.001). The mean levels of haemoglobin, packed cell volume, reticulocyte count, platelets count, lymphocytes, eosinophils, and serum iron were significantly lower while total leukocytes, immature granulocytes, monocytes, erythrocyte sedimentation rate, transferrin saturation, and serum ferritin were significantly higher in HbAA-infected children than HbAS-infected children. Infection with Plasmodium falciparum malaria caused more significant haematological alterations of HbAA children than HbAS. This study supports the observation that sickle cell trait seems to be a beneficial genetic factor that resists malaria, since inheriting it protects against significant haematological consequences of malaria.

Polymorphism and haplotype analyses of swine leukocyte antigen DQA exons 2, 3, 4, and their associations with piglet diarrhea in Chinese native pig.

PubMed

Huang, X Y; Yang, Q L; Yuan, J H; Gun, S B

2015-09-08

In this study, 290 Chinese native Yantai black pig piglets were investigated to identify gene polymorphisms, for haplotype reconstruction, and to determine the association between piglet diarrhea and swine leukocyte antigen (SLA) class II DQA exons 2, 3, and 4 by polymerase chain reaction-single stranded conformational polymorphism and cloning sequencing. The results showed that the 5, 8, and 7 genotypes were identified from SLA-DQA exon 2, 3, and 4, respectively, based on the single-stranded conformational polymorphism banding patterns and found a novel allele D in exon 2 and 2 novel mutational sites of allele C (c.4828T>C) and allele F (c.4617T>C) in exon 3. Polymorphism information content testing showed that exon 2 was moderately polymorphic and that exons-3 and -4 loci were highly polymorphic. The piglet diarrhea scores for genotypes AB (1.40 ± 0.14) and AC (1.54 ± 0.17) in exon 2, AA (1.22 ± 0.32), BC (1.72 ± 0.13), DD (1.67 ± 0.35), and CF (1.22 ± 0.45) in exon 3, and AD (2.35 ± 0.25) in exon 4 were significantly higher than those for the other genotypes (P ≤ 0.05) in DQA exons. There were 14 reconstructed haplotypes in the 3 exons from 290 individuals and Hap12 may be the diarrhea-resistant gene. Haplotype distribution was extremely uneven, and the SLA-DQA gene showed genetic linkage. In this study, we identified molecular genetic markers and provided a theoretical foundation for future pig anti-disease resistance breeding.

Pandemic influenza A/H1N1 virus infection and TNF, LTA, IL1B, IL6, IL8, and CCL polymorphisms in Mexican population: a case–control study

PubMed Central

2012-01-01

Background Some patients have a greater response to viral infection than do others having a similar level of viral replication. Hypercytokinemia is the principal immunopathological mechanism that contributes to a severer clinical course in cases of influenza A/H1N1. The benefit produced, or damage caused, by these cytokines in severe disease is not known. The genes that code for these molecules are polymorphic and certain alleles have been associated with susceptibility to various diseases. The objective of the present study was to determine whether there was an association between polymorphisms of TNF, LTA, IL1B, IL6, IL8, and CCL1 and the infection and severity of the illness caused by the pandemic A/H1N1 in Mexico in 2009. Methods Case–control study. The cases were patients confirmed with real time PCR with infection by the A/H1N1 pandemic virus. The controls were patients with infection like to influenza and non-familial healthy contacts of the patients with influenza. Medical history and outcome of the disease was registered. The DNA samples were genotyped for polymorphisms TNF rs361525, rs1800629, and rs1800750; LTA rs909253; IL1B rs16944; IL6 rs1818879; IL8 rs4073; and CCL1 rs2282691. Odds ratio (OR) and the 95% confidence interval (95% CI) were calculated. The logistic regression model was adjusted by age and severity of the illness in cases. Results Infection with the pandemic A/H1N1 virus was associated with the following genotypes: TNF rs361525 AA, OR = 27.00; 95% CI = 3.07–1248.77); LTA rs909253 AG (OR = 4.33, 95% CI = 1.82–10.32); TNF rs1800750 AA (OR = 4.33, 95% CI = 1.48–12.64); additionally, LTA rs909253 AG showed a limited statistically significant association with mortality (p = 0.06, OR = 3.13). Carriers of the TNF rs1800629 GA genotype were associated with high levels of blood urea nitrogen (p = 0.05); those of the TNF rs1800750 AA genotype, with high levels of creatine phosphokinase (p=0.05). The IL1B rs16944 AA genotype was associated with an elevated number of leukocytes (p <0.001) and the IL8 rs4073 AA genotype, with a higher value for PaO2 mm Hg. Conclusion The polymorphisms of genes involved in the inflammatory process contributed to the severity of the clinical behavior of infection by the pandemic influenza A/H1N1 virus. PMID:23148654

Pandemic influenza A/H1N1 virus infection and TNF, LTA, IL1B, IL6, IL8, and CCL polymorphisms in Mexican population: a case-control study.

PubMed

Morales-García, Guadalupe; Falfán-Valencia, Ramcés; García-Ramírez, Román Alejandro; Camarena, Ángel; Ramirez-Venegas, Alejandra; Castillejos-López, Manuel; Pérez-Rodríguez, Martha; González-Bonilla, César; Grajales-Muñíz, Concepción; Borja-Aburto, Víctor; Mejía-Aranguré, Juan Manuel

2012-11-13

Some patients have a greater response to viral infection than do others having a similar level of viral replication. Hypercytokinemia is the principal immunopathological mechanism that contributes to a severer clinical course in cases of influenza A/H1N1. The benefit produced, or damage caused, by these cytokines in severe disease is not known. The genes that code for these molecules are polymorphic and certain alleles have been associated with susceptibility to various diseases. The objective of the present study was to determine whether there was an association between polymorphisms of TNF, LTA, IL1B, IL6, IL8, and CCL1 and the infection and severity of the illness caused by the pandemic A/H1N1 in Mexico in 2009. Case-control study. The cases were patients confirmed with real time PCR with infection by the A/H1N1 pandemic virus. The controls were patients with infection like to influenza and non-familial healthy contacts of the patients with influenza. Medical history and outcome of the disease was registered. The DNA samples were genotyped for polymorphisms TNF rs361525, rs1800629, and rs1800750; LTA rs909253; IL1B rs16944; IL6 rs1818879; IL8 rs4073; and CCL1 rs2282691. Odds ratio (OR) and the 95% confidence interval (95% CI) were calculated. The logistic regression model was adjusted by age and severity of the illness in cases. Infection with the pandemic A/H1N1 virus was associated with the following genotypes: TNF rs361525 AA, OR = 27.00; 95% CI = 3.07-1248.77); LTA rs909253 AG (OR = 4.33, 95% CI = 1.82-10.32); TNF rs1800750 AA (OR = 4.33, 95% CI = 1.48-12.64); additionally, LTA rs909253 AG showed a limited statistically significant association with mortality (p = 0.06, OR = 3.13). Carriers of the TNF rs1800629 GA genotype were associated with high levels of blood urea nitrogen (p = 0.05); those of the TNF rs1800750 AA genotype, with high levels of creatine phosphokinase (p=0.05). The IL1B rs16944 AA genotype was associated with an elevated number of leukocytes (p <0.001) and the IL8 rs4073 AA genotype, with a higher value for PaO2 mm Hg. The polymorphisms of genes involved in the inflammatory process contributed to the severity of the clinical behavior of infection by the pandemic influenza A/H1N1 virus.

Functional Mu Opioid Receptor Polymorphism (OPRM1 A118G) Associated With Heroin Use Outcomes in Caucasian Males: A Pilot Study

PubMed Central

Woodcock, Eric A.; Lundahl, Leslie H.; Burmeister, Margit; Greenwald, Mark K.

2017-01-01

Background Heroin’s analgesic, euphoric and dependence-producing effects are primarily mediated by the mu opioid receptor (MOR). A single gene, OPRM1, encodes the MOR. The functional polymorphism A118G, located in exon 1 of the OPRM1 gene, results in anatomically-specific reductions in MOR expression, which may alter an individual’s response to heroin. In prior studies 118G (rare allele) carriers demonstrated significantly greater opioid tolerance, overdose vulnerability, and pain sensitivity than 118AA homozygotes. Those findings suggest OPRM1 genotype may impact characteristics of heroin use. Methods The present pilot study characterized the impact of OPRM1 genotype (rs1799971, 118G allele carriers vs. 118AA homozygotes) on heroin-use phenotypes associated with heroin dependence severity in a sample of male, Caucasian chronic heroin users (n = 86). Results Results indicate that 118G allele carriers reported significantly more heroin use-related consequences and heroin-quit attempts, and were more likely to have sought treatment for their heroin use than 118AA homozygotes. Conclusions These preliminary findings, consistent with extant data, illustrate a role for OPRM1 allelic variation on heroin use characteristics, and provide support for considering genotype in heroin treatment and relapse prevention. PMID:25911999

Association Between Insulin-Like Growth Factor Binding Protein-3 Promoter Polymorphism of −1590 C>A and Lung Cancer Susceptibility in a Chinese Han Population

PubMed Central

Dai, Xiaofang; Liu, Zhao; Ren, Jinghua

2011-01-01

Recent studies have identified a negative correlation between serum levels of insulin-like growth factor binding protein-3 (IGFBP-3) and the risk of lung cancer. In this study, polymorphisms present at the −1590 site of the IGFBP-3 promoter were evaluated in relation to lung cancer risk in a Chinese Han population. A total of 248 nonsmall cell lung cancer (NSCLC) cases and 29 small cell lung cancer cases were compared with 252 matched, healthy controls. Polymerase chain reaction-based restriction fragment length polymorphism assays were used to detect polymorphisms present. The A/A genotype and an A allele were both associated with an increased risk of NSCLC after being adjusted for age and gender (adjusted odds ratio = 2.296, 95% confidence interval = 1.133–4.655; and adjusted odds ratio = 1.390, 95% confidence interval = 1.042–1.854, respectively). In conclusion, the A/A genotype and A allele of the IGFBP-3 promoter −1590 site may represent a genetic risk factor for NSCLC, with the A/A genotype being associated with a higher risk for squamous cell carcinoma than adenocarcinoma. PMID:21254935

Association of Mannose-Binding Lectin rs1800450 and Tumor Necrotic Factor-α rs1800620 Polymorphism with Helicobacter pylori in Type II Diabetes Mellitus.

PubMed

Mortazavi, Elnaz; Eslami, Behnaz; Aghahosseini, Parisa; Ahron, Fatemeh; Amininejad, Armagan; Mahmoodi, Sepideh; Satarpour, Hadis; Radmanesh, Nilofar; Rassi, Hossein

2017-10-01

Type II diabetes mellitus (T2DM) is the prevalent type of diabetes, including 90% of the cases world-wide. Helicobacter pylori plays a pathogenic role in the development of T2DM. The host genetic factors have a significant impact on the clinical outcome and anatomical distribution of H. pylori infection and polymorphisms in several genes such as tumor necrotic factor (TNF)-α and mannose-binding lectin (MBL) and are considered to increase the risk for the development of T2DM. In this study, we investigate the prevalence rate of H. pylori infection and its relationship to MBL rs1800450 and TNF-α rs1800620 polymorphism in T2DM. In this case-control study, 174 patients with type II diabetes and 185 healthy controls were studied. Also, demographics, physical, and biochemical parameters were performed in all patients. The DNA extracted from blood specimens was amplified by H. pylori cagA-specific primers. The MBL rs1800450 and TNF-α rs1800620 genotyping were detected by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). The results show that H. pylori cagA positivity was detected in 42.82% of the diabetic patients and in 22.16% of the control group, and H. pylori infection was closely correlated with MBL rs1800450 AA genotype and TNF-α rs1800620 GG genotype when compared with healthy controls. Furthermore, these two genotypes were strongly associated with H. pylori cagA(+) samples when compared with cagA(-) samples. In addition, the presence of H. pylori cagA(+) infection was significantly associated with the elevated serum levels of total cholesterol and low-density lipoprotein cholesterol. In general, it can be concluded that molecular analysis of MBL rs1800450 AA genotype and TNF-α rs1800620 AA genotype is important in the early detection and treatment of T2DM with H. pylori cagA(+) infection.

Association of tumour necrosis factor-α polymorphism in patients with end stage renal disease.

PubMed

Singh, Kamini; Prasad, Kashi Nath; Mishra, Priyanka; Singh, Satyendra Kumar; Kharwar, Nagendra Kumar; Prasad, Narayan; Gupta, Amit; Srivastava, Janmejai Kumar

2015-06-01

Cytokines play a critical role in the pathophysiology of end stage renal disease (ESRD). Tumour necrosis factor-a (TNF-α) is an important cytokine involved in initiation and progression of renal diseases. The present study evaluated the association of specific alleles/genotype of TNF-α with chronic renal failure (CRF) and ESRD. A total of 30 CRF patients who were not on renal replacement therapy, 85 ESRD patients and 120 healthy controls were included in the study. The ESRD patients belonged to two subgroups: patients on peritoneal dialysis (PD) without peritonitis (n = 50) and with peritonitis (n = 35). TNF-α genotype (-308 G > A) was determined by polymerase chain reaction-restriction fragment length polymorphism. Level of TNF-α was detected in the sera of patients and healthy controls by enzyme linked immunosorbent assay (ELISA), and also in the dialysate of patients on PD. The genotypic distributions of TNF-α (-308 G > A) were significantly different between patients and controls. Homozygous A/A genotype had significant association with CRF and ESRD (P < 0.001, odds ratio [OR] = 25.02). Frequency of homozygous A/A genotype was significantly higher in all subgroups of patients than controls (CRF 40% vs control 2.5%, P = 0.001; PD 54% vs control 2.5%, P < 0.001 and PD with peritonitis 62.8% vs control 2.5%, P < 0.001). Patients with homozygous A/A genotype had significantly elevated levels of TNF-α in the sera of patients and in the dialysate of PD patients. Individuals with homozygous TNF-α (-308 G > A) polymorphisms has significant association with CRF and ESRD, and thus may be a predictor for development of the disease. Elevated TNF-α may be a contributory factor. © 2015 Asian Pacific Society of Nephrology.

A genetic variant of NLRP1 gene is associated with asbestos body burden in patients with malignant pleural mesothelioma.

PubMed

Crovella, S; Moura, R R; Cappellani, S; Celsi, F; Trevisan, E; Schneider, M; Brollo, A; Nicastro, E M; Vita, F; Finotto, L; Zabucchi, G; Borelli, V

2018-01-01

The presence of asbestos bodies (ABs) in lung parenchyma is considered a histopathologic hallmark of past exposure to asbestos fibers, of which there was a population of longer fibers. The mechanisms underlying AB formation are complex, involving inflammatory responses and iron (Fe) metabolism. Thus, the responsiveness to AB formation is variable, with some individuals appearing to be poor AB formers. The aim of this study was to disclose the possible role of genetic variants of genes encoding inflammasome and iron metabolism proteins in the ability to form ABs in a population of 81 individuals from North East Italy, who died after having developed malignant pleural mesothelioma (MPM). This study included 86 genetic variants distributed in 10 genes involved in Fe metabolism and 7 genetic variants in two genes encoding for inflammasome molecules. Genotypes/haplotypes were compared according to the number of lung ABs. Data showed that the NLRP1 rs12150220 missense variant (H155L) was significantly correlated with numbers of ABs in MPM patients. Specifically, a low number of ABs was detected in individuals carrying the NLRP1 rs12150220 A/T genotype. Our findings suggest that the NLRP1 inflammasome might contribute in the development of lung ABs. It is postulated that the NLRP1 missense variant may be considered as one of the possible host genetic factors contributing to individual variability in coating efficiency, which needs to be taken when assessing occupational exposure to asbestos.

Association of the proprotein convertase subtilisin/kexin-type 2 (PCSK2) gene with type 2 diabetes in an African American population

PubMed Central

Leak, Tennille S.; Keene, Keith L.; Langefeld, Carl D.; Gallagher, Carla J.; Mychaleckyj, Josyf C.; Freedman, Barry I.; Bowden, Donald W.; Rich, Stephen S.; Sale, Michèle M.

2009-01-01

In a genome-wide scan for type 2 diabetes (T2DM) in African American (AA) families, ordered subsets analysis (OSA) provided evidence for linkage to chromosome 20p in a subset with later age at diagnosis (max. LOD 2.57, P = 0.008). The proprotein convertase subtilisin/kexin-type 2 (PCSK2) gene is within the LOD-1 interval of this linkage peak. Twenty-nine single nucleotide polymorphisms (SNPs) were genotyped across this gene in 380 unrelated AA individuals with T2DM and end-stage renal disease (T2DM-ESRD), 278 AA controls, 96 European Americans (EA) and 120 Yoruba Nigerian (YRI) controls. In addition, 22 ancestry-informative markers (AIMs) were genotyped in all AA subjects, 120 YRI, and 96 EA controls. ADMIXMAP was used to model the distributions of admixture and generate score tests of allelic and haplotypic association. Association with T2DM was observed among 4 SNPs: rs2021785 (admixture-adjusted Pa = 0.00014), rs1609659 (Pa = 0.028), rs4814597 (Pa = 0.039) and rs2269023 (Pa = 0.043). None of the PCSK2 SNPs were associated with age at T2DM diagnosis. A variant in the PCKS2 gene, rs2021785, appears to play a role in susceptibility to T2DM in this AA population. PMID:17618154

A meta-analysis of interleukin-10-1082 promoter genetic polymorphism associated with atherosclerotic risk.

PubMed

Chao, Li; Lei, Huang; Fei, Jin

2014-01-01

This meta-analysis was conducted to assess the relationship between interleukin-10-1082 G/A single nucleotide polymorphism with atherosclerosis (AS) risk. The databases of PubMed, EMBASE, Chinese National Knowledge Infrastructure and Wan-Fang were searched from January 2000 to January 2014. 16 studies (involving 7779 cases and 7271 controls) were finally included. Each eligible study was scored for quality assessment. We adopted the most probably appropriate genetic model (recessive model) after carefully calculation. Between study heterogeneity was explored by subgroup analysis and publication bias was estimated by Begg's funnel plot and Egger's regression test. Statistically significant association was observed between AA genotype with overall AS risk, being mainly in coronary heart disease and stroke subgroups among Asian population, and peripheral artery disease (PAD) subgroup among Caucasians. Interleukin-10-1082 AA genotype is associated with increased overall AS risk. AA carriers of Asians seem to be more susceptible to coronary artery disease and stroke, and Caucasians are more susceptible to PAD.

Interleukin-2 and Interleukin-8 Gene Polymorphisms and Acquired Aplastic Anemia Risk in a Chinese Population.

PubMed

Zhang, Xuejie; Lin, Shengyun; Yang, Yan; Rong, Liucheng; He, Guangsheng; He, Hailong; Xue, Yao; Fang, Yongjun; Wang, Yaping

2017-01-01

Cytokines IL-2 and IL-8 both participate in immune regulation. However, the relationship between polymorphisms in these two cytokines and the risk of acquired aplastic anemia (acquired AA) has not been explored. We selected five SNPs including rs11575812, rs2069772 and rs2069762 of IL-2, rs2227306 and rs2227543 of IL-8. SNaPshot genotyping was used to test the genotypes of IL-2 and IL-8 polymorphisms in a population of 101 acquired AA patients and 165 healthy controls. The rs2069762 G allele appeared to be a protective mutation, but no significant differences were found in other four SNPs. We also found that rs2069762 had an impact on the transcriptional regulation. It could be assumed that the rs2069762 polymorphism might reduce the risk of acquired aplastic anemia, while the remaining four SNPs might not contribute to susceptibility to acquired AA in a Chinese population. © 2017 The Author(s)Published by S. Karger AG, Basel.

A Collaborative Study of the Etiology of Breast Cancer Subtypes in African American Women: the AMBER Consortium

PubMed Central

Palmer, Julie R.; Ambrosone, Christine B.; Olshan, Andrew F.

2014-01-01

Purpose Breast cancer is a heterogeneous disease, with at least five intrinsic subtypes defined by molecular characteristics. Tumors that express the estrogen receptor (ER+) have better outcomes than ER− tumors, due in part to the success of hormonal therapies that target ER+ tumors. The incidence of ER− breast cancer, and the subset of ER− cancers that are basal-like, is about twice as high among African American (AA) women as among U.S. women of European descent (EA). This disparity appears to explain, in part, the disproportionately high mortality from breast cancer that occurs in AA women. Epidemiologic research on breast cancer in AA women lags behind research in EA women. Here, we review differences in the etiology of breast cancer subtypes among AA women and describe a new consortium of ongoing studies of breast cancer in AA women. Methods We combined samples and data from four large epidemiologic studies of breast cancer in AA women, two cohort and two case-control, creating the AMBER consortium. Tumor tissue is obtained and stored in tissue microarrays, with assays of molecular markers carried out at a pathology core. Genotyping, carried out centrally, includes a whole exome SNP array and over 180,000 custom SNPs for fine-mapping of GWAS loci and candidate pathways. Results To date, questionnaire data from 5,739 breast cancer cases and 14,273 controls have been harmonized. Genotyping of the first 3,200 cases and 3,700 controls is underway, with a total of 6,000 each expected by the end of the study period. Conclusions The new consortium will likely have sufficient statistical power to assess potential risk factors, both genetic and non-genetic in relation to specific subtypes of breast cancer in AA women. PMID:24343304

Kindlin-2 directly binds actin and regulates integrin outside-in signaling

PubMed Central

Bledzka, Kamila; Bialkowska, Katarzyna; Sossey-Alaoui, Khalid; Vaynberg, Julia; Pluskota, Elzbieta

2016-01-01

Reduced levels of kindlin-2 (K2) in endothelial cells derived from K2+/− mice or C2C12 myoblastoid cells treated with K2 siRNA showed disorganization of their actin cytoskeleton and decreased spreading. These marked changes led us to examine direct binding between K2 and actin. Purified K2 interacts with F-actin in cosedimentation and surface plasmon resonance analyses and induces actin aggregation. We further find that the F0 domain of K2 binds actin. A mutation, LK47/AA, within a predicted actin binding site (ABS) of F0 diminishes its interaction with actin by approximately fivefold. Wild-type K2 and K2 bearing the LK47/AA mutation were equivalent in their ability to coactivate integrin αIIbβ3 in a CHO cell system when coexpressed with talin. However, K2-LK47/AA exhibited a diminished ability to support cell spreading and actin organization compared with wild-type K2. The presence of an ABS in F0 of K2 that influences outside-in signaling across integrins establishes a new foundation for considering how kindlins might regulate cellular responses. PMID:27044892

The Complete Genome Phylogeny of Geographically Distinct Dengue Virus Serotype 2 Isolates (1944-2013) Supports Further Groupings within the Cosmopolitan Genotype

PubMed Central

Ali, Akhtar; Ali, Ijaz

2015-01-01

Dengue virus serotype 2 (DENV-2) isolates have been implicated in deadly outbreaks of dengue fever (DF) and dengue hemorrhagic fever (DHF) in several regions of the world. Phylogenetic analysis of DENV-2 isolates collected from particular countries has been performed using partial or individual genes but only a few studies have examined complete whole-genome sequences collected worldwide. Herein, 50 complete genome sequences of DENV-2 isolates, reported over the past 70 years from 19 different countries, were downloaded from GenBank. Phylogenetic analysis was conducted and evolutionary distances of the 50 DENV-2 isolates were determined using maximum likelihood (ML) trees or Bayesian phylogenetic analysis created from complete genome nucleotide (nt) and amino acid (aa) sequences or individual gene sequences. The results showed that all DENV-2 isolates fell into seven main groups containing five previously defined genotypes. A Cosmopolitan genotype showed further division into three groups (C-I, C-II, and C-III) with the C-I group containing two subgroups (C-IA and C-IB). Comparison of the aa sequences showed specific mutations among the various groups of DENV-2 isolates. A maximum number of aa mutations was observed in the NS5 gene, followed by the NS2A, NS3 and NS1 genes, while the smallest number of aa substitutions was recorded in the capsid gene, followed by the PrM/M, NS4A, and NS4B genes. Maximum evolutionary distances were found in the NS2A gene, followed by the NS4A and NS4B genes. Based on these results, we propose that genotyping of DENV-2 isolates in future studies should be performed on entire genome sequences in order to gain a complete understanding of the evolution of various isolates reported from different geographical locations around the world. PMID:26414178

CRTC2 polymorphism as a risk factor for the incidence of metabolic syndrome in patients with solid organ transplantation.

PubMed

Quteineh, L; Bochud, P-Y; Golshayan, D; Crettol, S; Venetz, J-P; Manuel, O; Kutalik, Z; Treyer, A; Lehmann, R; Mueller, N J; Binet, I; van Delden, C; Steiger, J; Mohacsi, P; Dufour, J-F; Soccal, P M; Pascual, M; Eap, C B

2017-01-01

Metabolic syndrome after transplantation is a major concern following solid organ transplantation (SOT). The CREB-regulated transcription co-activator 2 (CRTC2) regulates glucose metabolism. The effect of CRTC2 polymorphisms on new-onset diabetes after transplantation (NODAT) was investigated in a discovery sample of SOT recipients (n 1 =197). Positive results were tested for replication in two samples from the Swiss Transplant Cohort Study (STCS, n 2 =1294 and n 3 =759). Obesity and other metabolic traits were also tested. Associations with metabolic traits in population-based samples (n 4 =46'186, n 5 =123'865, n 6 >100,000) were finally analyzed. In the discovery sample, CRTC2 rs8450-AA genotype was associated with NODAT, fasting blood glucose and body mass index (P corrected <0.05). CRTC2 rs8450-AA genotype was associated with NODAT in the second STCS replication sample (odd ratio (OR)=2.01, P=0.04). In the combined STCS replication samples, the effect of rs8450-AA genotype on NODAT was observed in patients having received SOT from a deceased donor and treated with tacrolimus (n=395, OR=2.08, P=0.02) and in non-kidney transplant recipients (OR=2.09, P=0.02). Moreover, rs8450-AA genotype was associated with overweight or obesity (n=1215, OR=1.56, P=0.02), new-onset hyperlipidemia (n=1007, OR=1.76, P=0.007), and lower high-density lipoprotein-cholesterol (n=1214, β=-0.08, P=0.001). In the population-based samples, a proxy of rs8450G>A was significantly associated with several metabolic abnormalities. CRTC2 rs8450G>A appears to have an important role in the high prevalence of metabolic traits observed in patients with SOT. A weak association with metabolic traits was also observed in the population-based samples.

[Correlation between the genetic polymorphisms of apolipoprotein M with the susceptibility to rheumatic diseases of Chinese Han populastion in Lanzhou].

PubMed

Li, Meiyong; Guo, Xinling; Li, Qiannan; You, Chongge

2016-08-01

Objective To investigate the relationship between the genetic polymorphisms of apolipoprotein M (ApoM) and the susceptibility to rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and ankylosing spondylitis (AS) among Chinese Han population in Lanzhou. Methods Primers for the two single nucleotide polymorphism (SNP) sites (rs805296 and rs805297) in ApoM gene were designed and their genotyping methods of polymerase chain reaction-high resolution melting (PCR-HRM) assay were established. Case-control studies were performed among the 599 cases of RA, 194 cases of SLE, 179 cases of AS and 273 matched healthy controls to analyze the correlations between the two SNPs and the susceptibility to rheumatic diseases. Results The genotype frequencies of rs805296 were AA 87.0%, AG 12.7%, GG 0.3% in RA cases, AA 84.5%, AG 15.0%, GG 0.5% in SLE cases, AA 91.6%, AG 7.3%, GG 1.1% in AS cases, AA 85.0%, AG 15.0%, GG 0% in healthy controls. The ones of rs805297 were GG 38.2%, GT 51.8%, TT 10.0% in RA cases, GG 44.3%, GT 45.4%, TT 10.3% in SLE cases, GG 37.4%, GT 47.5%, TT 15.1% in AS cases, GG 40.7%, GT 46.1%, TT 13.2% in healthy controls. Statistical analyses showed that only the genotype distribution of rs805296 was significantly different between the AS cases and the healthy controls. Under the dominant model, the G allele carriers of rs805296 (AG heterozygote and GG homozygote) were found to significantly decrease the risk for AS development. Conclusion The established PCR-HRM genotyping assays in the present study can successfully achieve the molecular diagnosis of the two SNPs sites (rs805296 and rs805297) from clinical samples, and the study found a significant association between the SNP of rs805296 and the susceptibility to AS among Chinese Han population in Lanzhou.

Associations between CD36 gene polymorphisms and susceptibility to coronary artery heart disease

PubMed Central

Zhang, Y.; Ling, Z.Y.; Deng, S.B.; Du, H.A.; Yin, Y.H.; Yuan, J.; She, Q.; Chen, Y.Q.

2014-01-01

Associations between polymorphisms of the CD36 gene and susceptibility to coronary artery heart disease (CHD) are not clear. We assessed allele frequencies and genotype distributions of CD36 gene polymorphisms in 112 CHD patients and 129 control patients using semi-quantitative polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Additionally, we detected CD36 mRNA expression by real-time quantitative PCR, and we quantified plasma levels of oxidized low-density lipoprotein (ox-LDL) using an enzyme-linked immunosorbent assay (ELISA). There were no significant differences between the two groups (P>0.05) in allele frequencies of rs1761667 or in genotype distribution and allele frequencies of rs3173798. The genotype distribution of rs1761667 significantly differed between CHD patients and controls (P=0.034), with a significantly higher frequency of the AG genotype in the CHD group compared to the control group (P=0.011). The plasma levels of ox-LDL in patients with the AG genotype were remarkably higher than those with the GG and AA genotypes (P=0.010). In a randomized sample taken from patients in the two groups, the CD36 mRNA expression of the CHD patients was higher than that of the controls. In CHD patients, the CD36 mRNA expression in AG genotype patients was remarkably higher than in those with an AA genotype (P=0.005). After adjusted logistic regression analysis, the AG genotype of rs1761667 was associated with an increased risk of CHD (OR=2.337, 95% CI=1.336-4.087, P=0.003). In conclusion, the rs1761667 polymorphism may be closely associated with developing CHD in the Chongqing Han population of China, and an AG genotype may be a genetic susceptibility factor for CHD. PMID:25118627

A first-principles study of the electrically tunable band gap in few-layer penta-graphene.

PubMed

Wang, Jinjin; Wang, Zhanyu; Zhang, R J; Zheng, Y X; Chen, L Y; Wang, S Y; Tsoo, Chia-Chin; Huang, Hung-Ji; Su, Wan-Sheng

2018-06-25

The structural and electronic properties of bilayer (AA- and AB-stacked) and tri-layer (AAA-, ABA- and AAB-stacked) penta-graphene (PG) have been investigated in the framework of density functional theory. The present results demonstrate that the ground state energy in AB stacking is lower than that in AA stacking, whereas ABA stacking is found to be the most energetically favorable, followed by AAB and AAA stackings. All considered model configurations are found to be semiconducting, independent of the stacking sequence. In the presence of a perpendicular electric field, their band gaps can be significantly reduced and completely closed at a specific critical electric field strength, demonstrating a Stark effect. These findings show that few-layer PG will have tremendous opportunities to be applied in nanoscale electronic and optoelectronic devices owing to its tunable band gap.

[Effect of cadmium chloride on immigration of mouse neural stem cell].

PubMed

Zhang, Yuyuan; Wang, Qunan; Chai, Xiaoyu; Shen, Zhongzhou; Gao, Liuwei

2015-01-01

To investigate the effects of cadmium chloride on cytoactive and immigration of mouse neural stem cell (mNSC). MTT assay was used to detect cytoactive at 24 hours. The immigration of mNSC was determined by immunofluorescence staining. Compared with control, CdCl2 treatment at 10.0 μmol/L for 24 h resulted in a decrease in cellular viability (70.08 ± 6.21)% (P < 0.05). Compared with control, Aa/Ab and Dm/Db display decreasing tendency in a dose-dependent manner (r(s Aa/Ab) = - 0.90, γ(s Dm/Db) = - 0.90, P < 0.05) after CdCl2 treatment at 0.1 - 10.0 μmol/L for 24 h. Cadmium chloride treatment inhibits immigration of mNSC, and shows negative effect on cell viability. Meanwhile, the effect of cadmium chloride on immigration is more obvious than cell viability at the same concentration for same treatment time.

Gene polymorphisms of TNF-alpha(-308), IL-10(-1082), IL-6(-174), and IL-1Ra(VNTR) related to susceptibility and severity of rheumatic heart disease.

PubMed

Settin, A; Abdel-Hady, H; El-Baz, R; Saber, I

2007-01-01

Rheumatic heart disease (RHD) is an inflammatory disease of the heart tissues caused by interactive immune, genetic, and environmental factors. The objective of this study is to test for the association of polymorphisms related to cytokine genes with susceptibility and severity of RHD among affected children from the Nile Delta region of Egypt. The study included 50 children with chronic RHD (29 males and 21 females), with a mean age of 12.2 years, in addition to 98 healthy unrelated controls. Cases were further classified on the basis of echocardiographic findings into those with only mitral valve disease (MVD) or multivalvular lesions (MVLs) and also as mild, moderate, or severe valve lesions. For all cases and controls, DNA was extracted and amplified using polymerase chain reaction with sequence-specific primers for detection of single nucleotide polymorphisms (SNPs) in the promoter regions of cytokine genes tumor necrosis factor (TNF)-alpha(-308 )G/A, interleukin (IL)-10(-1082 )G/A, and IL-6(-174 )G/C as well as a variable number of tandem repeats (VNTRs) in intron 2 of the IL-1Ra gene. All cases showed a significantly higher frequency of homozygous genotypes of TNF-alpha(-308 )A/A [odds ratio (OR) = 5.7, p < 0.001], IL-10(-1082) A/A (OR = 3.1, p < 0.05), IL-10(-1082) G/G (OR = 5.2, p < 0.05), and IL-1Ra A1/A1 (OR = 2.2, p < 0.05). Cases with MVD showed higher frequencies of genotypes TNF-alpha(-308 )A/A, G/G; IL-10(-1082) G/G; and IL-1Ra(VNTR) A1/A1 (p < 0.05). Cases with MVL showed a significantly higher frequency of homozygous A/A genotype of both TNF-alpha(-308 )(OR = 10.6, p < 0.05) and IL-10(-1082) (OR = 5.2, p < 0.05). The same was observed for cases with severe valve lesions. On the other hand, all studied groups showed significantly lower frequency of heterozygous genotypes of TNF-alpha(-308 )G/A, IL-10(-1082) G/A, and IL-1Ra(VNTR) A1/A2. No significant difference was found regarding the frequency of IL-6(-174 )G/C polymorphisms in total cases or subgroups compared to controls (p > 0.05). Predisposition to RHD is influenced by genetic factors including cytokine gene polymorphisms, with possible susceptibility to severe disease with multivalvular affection among cases with composite polymorphism (TNF-alpha(-308 )A/A and IL-10(-1082) A/A) and (TNF-alpha(-308 )A/A and IL-10(-1082) G/G).

USAF 1990 Research Initiation Program. Volume 3

DTIC Science & Technology

1992-06-25

the reinforcement outward, both on the entrance and exit sides. The reinforcement was bent outward like a membrane under internal prressure. This led...potential of a neuron. C: cell capacitance. R: membrane resistance. w: synaptic weight. h(x): sigmoidal function describing the firing rate. y: external...Proof: The uncertain closed loop plant may be written as x(t)=(A+AA)x(t)+(Ao+ AAo )x(t-T) (B+AB)F(C AC)x(t) =(A+BFC)x(t)+(AA+ABFC+BFAC+ABFAC)x(t)+(Ao+Ao)X(t

Frequency of Cry1F Non-Recessive Resistance Alleles in North Carolina Field Populations of Spodoptera frugiperda (Lepidoptera: Noctuidae)

PubMed Central

Li, Guoping; Reisig, Dominic; Miao, Jin; Gould, Fred; Huang, Fangneng; Feng, Hongqiang

2016-01-01

Fall armyworm, Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae), is a target species of transgenic corn (Zea mays L.) that expresses single and pyramided Bacillus thuringiensis (Bt) toxin. In 2014, S. frugiperda were collected from a light trap in North Carolina, and a total of 212 F1/F2 isofemale lines of S. frugiperda were screened for resistance to Bt and non-Bt corn. All of the 212 isolines were susceptible to corn tissue expressing Cry1A.105 + Cry2Ab, Cry1F + Cry1A.105 + Cry2Ab, and Cry1F + Cry1Ab + Vip3Aa20. Growth rate bioassays were performed to isolate non-recessive Bt resistance alleles. Seven individuals out of the 212 isofemale lines carried major non-recessive alleles conferring resistance to Cry1F. A pooled colony was created from the seven individuals. This colony was 151.21 times more resistant to Cry1F than a known-susceptible population and was also resistant to Cry1A.105, but was not resistant to Cry2Ab and Vip3Aa20. The results demonstrate that field populations of S. frugiperda collected from North Carolina are generally susceptible to Cry1F, but that some individuals carry resistant alleles. The data generated in this study can be used as baseline data for resistance monitoring. PMID:27119741

Frequency of Cry1F Non-Recessive Resistance Alleles in North Carolina Field Populations of Spodoptera frugiperda (Lepidoptera: Noctuidae).

PubMed

Li, Guoping; Reisig, Dominic; Miao, Jin; Gould, Fred; Huang, Fangneng; Feng, Hongqiang

2016-01-01

Fall armyworm, Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae), is a target species of transgenic corn (Zea mays L.) that expresses single and pyramided Bacillus thuringiensis (Bt) toxin. In 2014, S. frugiperda were collected from a light trap in North Carolina, and a total of 212 F1/F2 isofemale lines of S. frugiperda were screened for resistance to Bt and non-Bt corn. All of the 212 isolines were susceptible to corn tissue expressing Cry1A.105 + Cry2Ab, Cry1F + Cry1A.105 + Cry2Ab, and Cry1F + Cry1Ab + Vip3Aa20. Growth rate bioassays were performed to isolate non-recessive Bt resistance alleles. Seven individuals out of the 212 isofemale lines carried major non-recessive alleles conferring resistance to Cry1F. A pooled colony was created from the seven individuals. This colony was 151.21 times more resistant to Cry1F than a known-susceptible population and was also resistant to Cry1A.105, but was not resistant to Cry2Ab and Vip3Aa20. The results demonstrate that field populations of S. frugiperda collected from North Carolina are generally susceptible to Cry1F, but that some individuals carry resistant alleles. The data generated in this study can be used as baseline data for resistance monitoring.

Identification of SNP in HSP90AB1 and its association with the relative thermotolerance and milk production traits in Indian dairy cattle.

PubMed

Sajjanar, Basavaraj; Deb, Rajib; Singh, Umesh; Kumar, Sushil; Brahmane, Manoj; Nirmale, Avinash; Bal, Santanu Kumar; Minhas, P S

2015-01-01

Heat shock proteins (Hsp) play crucial role in cellular thermotolerance and heat stress response. In the present work, Allele specific PCR (AS-PCR) was standardized to detect the nucleotide polymorphism within the HSP90AB1 gene (SNP g.4338T>C) in Indian breeds of dairy cattle. The identified genotypes were associated with relative thermotolerance in terms of physiological parameters and milk production traits. The results of the experiments revealed that the genotype frequency of CC, CT, and TT for Sahiwal were 0.05, 0.78, and 0.17, respectively, and in Frieswal, the frequencies were 0.20, 0.70, and 0.10, respectively. The average rectal temperature (ART) and average respiration rates (ARR) were recorded during peak summer stress and heat tolerance coefficient (HTC) was calculated. The association studies indicated that TT genotypes had significantly (P < 0.01) higher HTC and lower ARR values than CT and CC in both the breeds. The TT genotype animals also had better production parameter in terms of total milk yield (TMY) (P < 0.01). These findings may partly suggest the role of HSP90AB1 polymorphisms in the regulation of heat stress response and consequent effect on production traits. Nevertheless, involvement of other regulatory mechanisms cannot be overruled.

Genetic Variants of TPCN2 Associated with Type 2 Diabetes Risk in the Chinese Population

PubMed Central

Zhang, Yu; Fan, Xiaofang; Zhang, Ning; Zheng, Hui; Song, Yuping; Shen, Chunfang; Shen, Jiayi; Ren, Fengdong; Yang, Jialin

2016-01-01

Objective The aim of this study was to determine whether TPCN2 genetic variants are associated with type 2 diabetes and to elucidate which variants in TPCN2 confer diabetes susceptibility in the Chinese population. Research Design and Methods The sample population included 384 patients with type 2 diabetes and 1468 controls. Anthropometric parameters, glycemic and lipid profiles and insulin resistance were measured. We selected 6 TPCN2 tag single nucleotide polymorphisms (rs35264875, rs267603153, rs267603154, rs3829241, rs1551305, and rs3750965). Genotypes were determined using a Sequenom MassARRAY SNP genotyping system. Results Ultimately, we genotyped 3 single nucleotide polymorphisms (rs3750965, rs3829241, and rs1551305) in all individuals. There was a 5.1% higher prevalence of the rs1551305 variant allele in type 2 diabetes individuals (A) compared with wild-type homozygous individuals (G). The AA genotype of rs1551305 was associated with a higher diabetes risk (p<0.05). The distributions of rs3829241 and rs3750965 polymorphisms were not significantly different between the two groups. HOMA-%B of subjects harboring the AA genotype of rs1551305 decreased by 14.87% relative to the GG genotype. Conclusions TPCN2 plays a role in metabolic regulation, and the rs1551305 single nucleotide polymorphism is associated with type 2 diabetes risk. Future work will begin to unravel the underlying mechanisms. PMID:26918892

Association of the Cocaine- and Amphetamine-Regulated Transcript Prepropeptide Gene (CARTPT) rs2239670 Variant with Obesity among Kampar Health Clinic Patrons, Malaysia.

PubMed

Lisa, Yeo; Sook-, Ha Fan; Yee-, How Say

2012-01-01

Cocaine- and amphetamine-regulated transcript (CART) is a hypothalamic anorectic neuropeptide that controls feeding behaviour and body weight. The study objective was to investigate the association of the CART prepropeptide gene (CARTPT) rs2239670 variant with obesity and its related anthropometric indicators among patients of a Malaysian health clinic in Kampar, Perak, Malaysia. A total of 300 Malay/Peninsular Bumiputera, Chinese, and Indian subjects (115 males, 185 females; 163 non-obese, 137 obese) were recruited by convenience sampling, and anthropometric measurements, blood pressures, and pulse rate were taken. Genotyping was performed using AvaII polymerase chain reaction-restriction fragment length polymorphism. Genotyping revealed 203 (67.7%), 90 (30.0%), and 7 (2.3%) subjects with the GG, GA, and AA genotypes, respectively, with a minor allele (A) frequency of 0.17. No significant difference in the CARTPT rs2239670 genotype and allele distribution was found between obese and non-obese subjects, and logistic regression showed no association between the mutated genotypes (GA, AA) and allele (A) with obesity, even after adjusting for age, gender, and ethnicity. Furthermore, the measurements did not differ significantly between the genotypes and alleles. No significant difference in the genotype and allele distribution was found among genders, but they were significantly different among ethnicities (P = 0.030 and P = 0.019, respectively). CARTPT rs2239670 is not a predictor for obesity among the Malaysian subjects in this study.

Polymorphisms in the LPL and CETP Genes and Haplotype in the ESR1 Gene Are Associated with Metabolic Syndrome in Women from Southwestern Mexico.

PubMed

Cahua-Pablo, José Ángel; Cruz, Miguel; Méndez-Palacios, Abigail; Antúnez-Ortiz, Diana Lizzete; Vences-Velázquez, Amalia; del Carmen Alarcón-Romero, Luz; Parra, Esteban Juan; Tello-Flores, Vianet Argelia; Leyva-Vázquez, Marco Antonio; Valladares-Salgado, Adán; Pérez-Macedonio, Claudia Paola; Flores-Alfaro, Eugenia

2015-09-08

Metabolic syndrome (MetS) is a combination of metabolic disorders associated with an increased risk for cardiovascular disease (CVD). Studies in women reported associations between polymorphisms in ESR1, LPL and CETP genes and MetS. Our aim was to evaluate the association between variants in ESR1, LPL and CETP genes with MetS and its components. Four hundred and eighty women were analyzed, anthropometric features and biochemical profiles were evaluated, and genotyping was performed by real-time PCR. We found an association with elevated glucose levels (odds ratio (OR) = 2.9; p = 0.013) in carrying the AA genotype of rs1884051 in the ESR1 gene compared with the GG genotype, and the CC genotype of rs328 in the LPL gene was associated with MetS compared to the CG or GG genotype (OR = 2.8; p = 0.04). Moreover, the GA genotype of rs708272 in the CETP gene is associated with MetS compared to the GG or AA genotype (OR = 1.8; p = 0.006). In addition the ACTCCG haplotype in the ESR1 gene is associated with a decrease in the risk of MetS (OR = 0.02; p < 0.001). In conclusion, our results show the involvement of the variants of ESR1, LPL and CETP genes in metabolic events related to MetS or some of its features.

Polymorphisms in the LPL and CETP Genes and Haplotype in the ESR1 Gene Are Associated with Metabolic Syndrome in Women from Southwestern Mexico

PubMed Central

Cahua-Pablo, José Ángel; Cruz, Miguel; Méndez-Palacios, Abigail; Antúnez-Ortiz, Diana Lizzete; Vences-Velázquez, Amalia; del Carmen Alarcón-Romero, Luz; Parra, Esteban Juan; Tello-Flores, Vianet Argelia; Leyva-Vázquez, Marco Antonio; Valladares-Salgado, Adán; Pérez-Macedonio, Claudia Paola; Flores-Alfaro, Eugenia

2015-01-01

Metabolic syndrome (MetS) is a combination of metabolic disorders associated with an increased risk for cardiovascular disease (CVD). Studies in women reported associations between polymorphisms in ESR1, LPL and CETP genes and MetS. Our aim was to evaluate the association between variants in ESR1, LPL and CETP genes with MetS and its components. Four hundred and eighty women were analyzed, anthropometric features and biochemical profiles were evaluated, and genotyping was performed by real-time PCR. We found an association with elevated glucose levels (odds ratio (OR) = 2.9; p = 0.013) in carrying the AA genotype of rs1884051 in the ESR1 gene compared with the GG genotype, and the CC genotype of rs328 in the LPL gene was associated with MetS compared to the CG or GG genotype (OR = 2.8; p = 0.04). Moreover, the GA genotype of rs708272 in the CETP gene is associated with MetS compared to the GG or AA genotype (OR = 1.8; p = 0.006). In addition the ACTCCG haplotype in the ESR1 gene is associated with a decrease in the risk of MetS (OR = 0.02; p < 0.001). In conclusion, our results show the involvement of the variants of ESR1, LPL and CETP genes in metabolic events related to MetS or some of its features. PMID:26370976

Shared Midgut Binding Sites for Cry1A.105, Cry1Aa, Cry1Ab, Cry1Ac and Cry1Fa Proteins from Bacillus thuringiensis in Two Important Corn Pests, Ostrinia nubilalis and Spodoptera frugiperda

PubMed Central

Hernández-Rodríguez, Carmen Sara; Hernández-Martínez, Patricia; Van Rie, Jeroen; Escriche, Baltasar; Ferré, Juan

2013-01-01

First generation of insect-protected transgenic corn (Bt-corn) was based on the expression of Cry1Ab or Cry1Fa proteins. Currently, the trend is the combination of two or more genes expressing proteins that bind to different targets. In addition to broadening the spectrum of action, this strategy helps to delay the evolution of resistance in exposed insect populations. One of such examples is the combination of Cry1A.105 with Cry1Fa and Cry2Ab to control O. nubilalis and S. frugiperda. Cry1A.105 is a chimeric protein with domains I and II and the C-terminal half of the protein from Cry1Ac, and domain III almost identical to Cry1Fa. The aim of the present study was to determine whether the chimeric Cry1A.105 has shared binding sites either with Cry1A proteins, with Cry1Fa, or with both, in O. nubilalis and in S. frugiperda. Brush-border membrane vesicles (BBMV) from last instar larval midguts were used in competition binding assays with 125I-labeled Cry1A.105, Cry1Ab, and Cry1Fa, and unlabeled Cry1A.105, Cry1Aa, Cry1Ab, Cry1Ac, Cry1Fa, Cry2Ab and Cry2Ae. The results showed that Cry1A.105, Cry1Ab, Cry1Ac and Cry1Fa competed with high affinity for the same binding sites in both insect species. However, Cry2Ab and Cry2Ae did not compete for the binding sites of Cry1 proteins. Therefore, according to our results, the development of cross-resistance among Cry1Ab/Ac, Cry1A.105, and Cry1Fa proteins is possible in these two insect species if the alteration of shared binding sites occurs. Conversely, cross-resistance between these proteins and Cry2A proteins is very unlikely in such case. PMID:23861865

TNF-α-308/-238 polymorphisms are associated with gastric cancer: A case-control family study in China.

PubMed

Xu, Yajuan; Cao, Xiaoqin; Jiang, Jicheng; Chen, Yi; Wang, Kaijuan

2017-02-01

Associations of TNF-α-308 (rs1800629) and -238 (rs361525) with gastric cancer had the inconsistent indication among different populations. In this case-control family study, 47 families were determined with the probands diagnosed with gastric cancer (case family, n=296), accordingly 47 families without gastric cancer were matched with the case families by multivariate distribution of age, sex, social class, and pedigree size (control family, n=319). Polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR) was used to identify the TNF genotype. Chi-square test was used to compare the groups regarding genotype and the allele frequencies, HWE test for Hardy-Weinberg equilibrium. The frequencies of TNF-α-308 GA and AA genotypes were significantly higher in case family than that in control family. The risk of gastric cancer was increased in GA and AA carriers in the first degree (OR=2.06, 95% CI=1.20-3.51 and OR=4.89, 95% CI=2.74-8.74), however the similar result was not found in the second degree. Helicobacter pylori infection status were significantly associated with risk of gastric cancer in first-degree relatives (OR=1.96, 95% CI=1.26-3.05) while no statistical significance was noted in the second-degree relatives. Haplotypes of TNF-α-308/-238 alleles, GA/GG, AA/GG and AA/GA indicated the susceptibilities to gastric cancer with OR and 95% confident intervals resulting 2.07 (1.34-3.21), 4.49 (2.74-7.33) and 4.98 (1.76-14.01) respectively. TNF-α-G308A (rs1800629) polymorphisms are associated with gastric cancer in Chinese population. Haplotypes of TNF-α-308/-238 GA/GG, AA/GG and AA/GA increase the susceptibilities to gastric cancer. The first-degree relatives are more likely to develop into gastric cancer with TNF-α-G308 polymorphisms and H. pylori positive than the second-degree are. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

[Effect of FABP2 gene G54A polymorphism on lipid and glucose metabolism in simple obesity children].

PubMed

Xu, Yunpeng; Rao, Xiaojiao; Hao, Min; Hou, Lijuan; Zhu, Xiaobo; Chang, Xiaotong

2016-01-01

To explore the relationship between intestinal fatty acid binding protein (FABP2) gene G54A polymorphism and simple childhood obesity, the effect of mutant 54A FABP2 gene on serum lipids and glucose metabolism. The total of 83 subjects with overweight/obesity and 100 subjects with healthy/normal weight were involved in this study. The G54A FABP2 gene allele and genotype frequencies between control group and overweight/obesity group were detected using polymerase chain reaction (PCR) -restriction fragment length polymorphism (RFLP) technology, and DNA sequences were confirmed by DNA sequencing. The automatic biochemical analyzer was used to detect fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels. Plasma insulin (Ins) was detected by radiation immune method, free fatty acids (FFA) was tested by ELISA method, insulin resistance index ( HOMA-IR ) was also calculated. The correlation between FABP2 G54A polymorphism and the development of children' obesity was analyzed. The relation between FABP2 G54A polymorphism and abnormal blood lipid and insulin resistance was assessed. The results of study on FABP2 gene polymorphism revealed as followed. In overweight/obese groups, the frequencies of GG, GA, AA genotypes was 33.7%, 49.4% and 16.9%, respectively. In control group, the frequencies of GG, GA, AA genotypes was 51. 0% , 40. 0% and 9. 0% , respectively. The differences between two groups was statistically significant (Χ2 = 6.27, P < 0.05). In overweight/obesity group, the frequencies of alleles were 58.4% for 54G and 41.6% for 54A. In control group, the frequencies of alleles were 71.0% for 54G and 29.0% for 54A. There was significant differences (Χ2 = 6.32, P < 0.05). The plasma biochemical variables results showed that compared with the normal control group, plasma TG (P < 0.01), Ins (P < 0.05), HOMA-IR (P < 0.05) were elevated in overweight/obesity group, the difference between two groups was statistically significant. At the same time, in overweight/obesity group, the carriers of AA homozygous genotypes had significantly higher plasma TG levels than those with GG wild genotypes (P < 0.05). A increased tendency of plasma Ins, FFA levels and HOMA-IR was found in the carriers with AA homozygous genotypes, but no differences compared with those with GG wild genotypes. Compared with those with GG wild genotypes, related plasma biochemical variables in the carriers with GA heterozygous genotypes had no differences (P > 0.05). The FABP2 gene G54A polymorphism is related to simple children obesity and lipid metabolism abnormality. The allele encoding in FABP2 gene may be a potential factor contributing to promoting lipid metabolism abnormality of and insulin resistance.

Serum Amyloid A Protein Concentration in Blood is Influenced by Genetic Differences in the Cheetah (Acinonyx jubatus).

PubMed

Franklin, Ashley D; Schmidt-Küntzel, Anne; Terio, Karen A; Marker, Laurie L; Crosier, Adrienne E

2016-03-01

Systemic amyloid A (AA) amyloidosis is a major cause of morbidity and mortality among captive cheetahs. The self-aggregating AA protein responsible for this disease is a byproduct of serum amyloid A (SAA) protein degradation. Transcriptional induction of the SAA1 gene is dependent on both C/EBPβ and NF-κB cis-acting elements within the promoter region. In cheetahs, 2 alleles exist for a single guanine nucleotide deletion in the putative NF-κB binding site. In this study, a novel genotyping assay was developed to screen for the alleles. The results show that the SAA1A (-97delG) allele is associated with decreased SAA protein concentrations in the serum of captive cheetahs (n = 58), suggesting genetic differences at this locus may be affecting AA amyloidosis prevalence. However, there was no significant difference in the frequency of the SAA1A (-97delG) allele between individuals confirmed AA amyloidosis positive versus AA amyloidosis negative at the time of necropsy (n = 48). Thus, even though there is evidence that having more copies of the SAA1A (-97delG) allele results in a potentially protective decrease in serum concentrations of SAA protein in captive cheetahs, genotype is not associated with this disease within the North American population. These results suggest that other factors are playing a more significant role in the pathogenesis of AA amyloidosis among captive cheetahs. © The American Genetic Association 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Variants in mannose‐binding lectin and tumour necrosis factor α affect survival in cystic fibrosis

PubMed Central

Buranawuti, Kitti; Boyle, Michael P; Cheng, Suzanne; Steiner, Lori L; McDougal, Kathryn; Fallin, M Daniele; Merlo, Christian; Zeitlin, Pamela L; Rosenstein, Beryl J; Mogayzel, Peter J; Wang, Xinjing; Cutting, Garry R

2007-01-01

Background Patients with cystic fibrosis with the same mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene differ widely in survival suggesting other factors have a substantial role in mortality. Objective To determine if the genotype distribution of variants in three putative cystic fibrosis modifier genes (tumour necrosis factor α (TNFα), transforming growth factor β1 (TGFβ1) or mannose‐binding lectin (MBL2)) differed among patients with cystic fibrosis grouped according to age and survival status. Methods Genotypes of four variants (TNFα‐238, TNFα‐308, TGFβ1‐509 and MBL2 O) were determined in three groups of Caucasians from a single medical centre: 101 children with cystic fibrosis (aged <17 years; mean age 9.4 years), 115 adults with cystic fibrosis (aged ⩾17 years; mean age 30.8 years) and 38 non‐surviving adults with cystic fibrosis (21 deceased and 17 lung transplant after 17 years of age). Genotypes of 127 healthy Caucasians in the same geographical region were used as controls. Kaplan–Meier and Cox hazard regression were used to evaluate the genotype effect on cumulative survival. Results Genotype frequencies among adults and children with cystic fibrosis differed for TNFα‐238 (G/G vs G/A; p = 0.022) and MBL2 (A/A vs O/O; p = 0.016). When adults with cystic fibrosis were compared to non‐surviving adults with cystic fibrosis, genotype frequencies of both genes differed (TNFα‐238G/G vs G/A; p =  0.0015 and MBL2: A/A vs O/O; p = 0.009). The hazard ratio for TNFα‐238G/G vs G/A was 0.25 (95% CI 0.06 to 1.0, p = 0.04) and for MBL2 O/O vs A/A or A/O was 2.5 (95% CI 1.3 to 4.9, p = 0.007). Conclusions TNFα‐238 G/A and MBL2 O/O genotypes appear to be genetic modifiers of survival of cystic fibrosis. PMID:17158822

A Quantitative Tool to Distinguish Isobaric Leucine and Isoleucine Residues for Mass Spectrometry-Based De Novo Monoclonal Antibody Sequencing

NASA Astrophysics Data System (ADS)

Poston, Chloe N.; Higgs, Richard E.; You, Jinsam; Gelfanova, Valentina; Hale, John E.; Knierman, Michael D.; Siegel, Robert; Gutierrez, Jesus A.

2014-07-01

De novo sequencing by mass spectrometry (MS) allows for the determination of the complete amino acid (AA) sequence of a given protein based on the mass difference of detected ions from MS/MS fragmentation spectra. The technique relies on obtaining specific masses that can be attributed to characteristic theoretical masses of AAs. A major limitation of de novo sequencing by MS is the inability to distinguish between the isobaric residues leucine (Leu) and isoleucine (Ile). Incorrect identification of Ile as Leu or vice versa often results in loss of activity in recombinant antibodies. This functional ambiguity is commonly resolved with costly and time-consuming AA mutation and peptide sequencing experiments. Here, we describe a set of orthogonal biochemical protocols, which experimentally determine the identity of Ile or Leu residues in monoclonal antibodies (mAb) based on the selectivity that leucine aminopeptidase shows for n-terminal Leu residues and the cleavage preference for Leu by chymotrypsin. The resulting observations are combined with germline frequencies and incorporated into a logistic regression model, called Predictor for Xle Sites (PXleS) to provide a statistical likelihood for the identity of Leu at an ambiguous site. We demonstrate that PXleS can generate a probability for an Xle site in mAbs with 96% accuracy. The implementation of PXleS precludes the expression of several possible sequences and, therefore, reduces the overall time and resources required to go from spectra generation to a biologically active sequence for a mAb when an Ile or Leu residue is in question.

A quantitative tool to distinguish isobaric leucine and isoleucine residues for mass spectrometry-based de novo monoclonal antibody sequencing.

PubMed

Poston, Chloe N; Higgs, Richard E; You, Jinsam; Gelfanova, Valentina; Hale, John E; Knierman, Michael D; Siegel, Robert; Gutierrez, Jesus A

2014-07-01

De novo sequencing by mass spectrometry (MS) allows for the determination of the complete amino acid (AA) sequence of a given protein based on the mass difference of detected ions from MS/MS fragmentation spectra. The technique relies on obtaining specific masses that can be attributed to characteristic theoretical masses of AAs. A major limitation of de novo sequencing by MS is the inability to distinguish between the isobaric residues leucine (Leu) and isoleucine (Ile). Incorrect identification of Ile as Leu or vice versa often results in loss of activity in recombinant antibodies. This functional ambiguity is commonly resolved with costly and time-consuming AA mutation and peptide sequencing experiments. Here, we describe a set of orthogonal biochemical protocols, which experimentally determine the identity of Ile or Leu residues in monoclonal antibodies (mAb) based on the selectivity that leucine aminopeptidase shows for n-terminal Leu residues and the cleavage preference for Leu by chymotrypsin. The resulting observations are combined with germline frequencies and incorporated into a logistic regression model, called Predictor for Xle Sites (PXleS) to provide a statistical likelihood for the identity of Leu at an ambiguous site. We demonstrate that PXleS can generate a probability for an Xle site in mAbs with 96% accuracy. The implementation of PXleS precludes the expression of several possible sequences and, therefore, reduces the overall time and resources required to go from spectra generation to a biologically active sequence for a mAb when an Ile or Leu residue is in question.

HD 156324: a tidally locked magnetic triple spectroscopic binary with a disrupted magnetosphere

NASA Astrophysics Data System (ADS)

Shultz, M.; Rivinius, Th; Wade, G. A.; Alecian, E.; Petit, V.

2018-03-01

HD 156324 is an SB3 (B2V/B5V/B5V) system in the Sco OB4 association. The He-strong primary possesses both a strong magnetic field and Hα emission believed to originate in its centrifugal magnetosphere. We analyse a large spectroscopic and high-resolution spectropolarimetric data set. The radial velocities (RVs) indicate that the system is composed of two subsystems, which we designate A and B. Period analysis of the RVs of the three components yields orbital periods Porb = 1.5806(1) d for the Aa and Ab components, and Porb = 6.67(2) d for the B component, a PGa star. Period analysis of the longitudinal magnetic field 〈Bz〉 and Hα equivalent widths, which should both be sensitive to the rotational period Prot of the magnetic Aa component, both yield ˜1.58 d. Since Porb = Prot Aa and Ab must be tidally locked. Consistent with this, the orbit is circularized, and the rotational and orbital inclinations are identical within uncertainty, as are the semimajor axis and the Kepler corotation radius. The star's Hα emission morphology differs markedly from both theoretical and observational expectations in that there is only one, rather than two, emission peaks. We propose that this unusual morphology may be a consequence of modification of the gravitocentrifugal potential by the presence of the close stellar companion. We also obtain upper limits on the magnetic dipole strength Bd for the Ab and B components, respectively, finding Bd < 2.6 and <0.7 kG.

Molecular characterization of human T-cell lymphotropic virus type 1 full and partial genomes by Illumina massively parallel sequencing technology.

PubMed

Pessôa, Rodrigo; Watanabe, Jaqueline Tomoko; Nukui, Youko; Pereira, Juliana; Casseb, Jorge; Kasseb, Jorge; de Oliveira, Augusto César Penalva; Segurado, Aluisio Cotrim; Sanabani, Sabri Saeed

2014-01-01

Here, we report on the partial and full-length genomic (FLG) variability of HTLV-1 sequences from 90 well-characterized subjects, including 48 HTLV-1 asymptomatic carriers (ACs), 35 HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and 7 adult T-cell leukemia/lymphoma (ATLL) patients, using an Illumina paired-end protocol. Blood samples were collected from 90 individuals, and DNA was extracted from the PBMCs to measure the proviral load and to amplify the HTLV-1 FLG from two overlapping fragments. The amplified PCR products were subjected to deep sequencing. The sequencing data were assembled, aligned, and mapped against the HTLV-1 genome with sufficient genetic resemblance and utilized for further phylogenetic analysis. A high-throughput sequencing-by-synthesis instrument was used to obtain an average of 3210- and 5200-fold coverage of the partial (n = 14) and FLG (n = 76) data from the HTLV-1 strains, respectively. The results based on the phylogenetic trees of consensus sequences from partial and FLGs revealed that 86 (95.5%) individuals were infected with the transcontinental sub-subtypes of the cosmopolitan subtype (aA) and that 4 individuals (4.5%) were infected with the Japanese sub-subtypes (aB). A comparison of the nucleotide and amino acids of the FLG between the three clinical settings yielded no correlation between the sequenced genotype and clinical outcomes. The evolutionary relationships among the HTLV sequences were inferred from nucleotide sequence, and the results are consistent with the hypothesis that there were multiple introductions of the transcontinental subtype in Brazil. This study has increased the number of subtype aA full-length genomes from 8 to 81 and HTLV-1 aB from 2 to 5 sequences. The overall data confirmed that the cosmopolitan transcontinental sub-subtypes were the most prevalent in the Brazilian population. It is hoped that this valuable genomic data will add to our current understanding of the evolutionary history of this medically important virus.

Associations of DNA polymorphisms in growth hormone and its transcriptional regulators with growth and carcass traits in two populations of Brangus bulls.

PubMed

Thomas, M G; Enns, R M; Shirley, K L; Garcia, M D; Garrett, A J; Silver, G A

2007-03-30

Sequence polymorphisms in the growth hormone (GH) gene and its transcriptional regulators, Pit-1 and Prop-1, were evaluated for associations with growth and carcass traits in two populations of Brangus bulls Chihuahuan Desert Rangeland Research Center (CDRRC, N = 248 from 14 sires) and a cooperating breeding program (COOP, N = 186 from 34 sires). Polymorphisms were SNP mutations in intron 4 (C/T) and exon V (C/G) in GH, A/G in exon VI in Pit-1, and A/G in exon III in Prop-1. In the COOP population, bulls of Pit-1 GG genotype had a significantly greater percentage of intramuscular fat than bulls of the AA or AG genotype, and bulls of the Prop-1 AA genotype had significantly greater scrotal circumference than bulls of AG or GG genotypes at ~365 days of age. Also, heterozygous genotypes for the two GH polymorphisms appeared advantageous for traits of muscularity and adiposity in the COOP population. The heterozygous genotype of GH intron 4 SNP was associated with advantages in weight gain, scrotal circumference, and fat thickness in the CDRRC population. The two GH polymorphisms accounted for >/=27.7% of the variation in these traits in the CDRRC population; however, R(2) was <5% in the COOP population. Based on haplotype analyses the two GH SNPs appeared to be in phase; the haplotype analyses also paralleled with the genotype analyses. Polymorphisms in GH and its transcriptional regulators appear to be predictors of growth and carcass traits in Brangus bulls, particularly those with heterozygous GH genotypes.

Association of methylenetetrahytrofolate reductase (MTHFR) C677T and A1298C polymorphisms with the susceptibility of childhood acute lymphoblastic leukaemia (ALL) in Chinese population

PubMed Central

2014-01-01

Background The aim of this study was to investigate the relationship between the polymorphisms of the methylenetetrahytrofolate reductase (MTHFR) gene and susceptibility to childhood acute lymphoblastic leukemia (ALL). Methods A case–control study was conducted among 98 children with ALL and 93 age- and sex- matched non-ALL controls. Genotyping of MTHFR C677T and A1298C polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The odds ratios (ORs) of MTHFR genotypes were used to assess the associations of these polymorphisms with childhood ALL susceptibility. Results No significant differences were observed for frequencies of the 677CC, 677CT and 677TT genotypes between patients and controls. Frequencies of the 1298AA, 1298 AC and 1298CC genotypes between the two groups were significantly different. The risk of ALL with the 1298C allele carriers (AC + CC) was elevated by 1.1 times compared with the AA genotype [OR = 2.100; 95% CI (1.149; 3.837); P = 0.015]. Conclusions The MTHFR A1298C polymorphism is associated with susceptibility to childhood ALL in the Chinese population. PMID:24476575

Genetic Characterization of Bacillus anthracis 17 JB strain.

PubMed

Seyed-Mohamadi, Sakineh; Moradi Bidhendi, Soheila; Tadayon, Keyvan; Ghaderi, Rainak

2015-06-01

Bacillus anthracis is one of the most homogenous bacteria ever described. Some level of diversity. Bacillus anthracis 17JB is a laboratory strain It is broadly used as a challenge strain in guinea pigs for potency test of anthrax vaccine. This work describes genetic characterization of B. anthracis 17 JB strain using the SNPs and MLVA genotyping. In SNPs typing, the originally French 17JB strain represented the A.Br. 008/009 subgroup. In Levy's genotyping method, 843, 451 and 864 bp long fragments were identified at AA03, AJ03 and AA07 loci, respectively. In the vaccine manufacturer perspective these findings are much valuable on their own account, but similar research is required to extend molecular knowledge of B. anthracis epidemiology in Persia.

Nicotine N-glucuronidation relative to N-oxidation and C-oxidation and UGT2B10 genotype in five ethnic/racial groups

PubMed Central

Murphy, Sharon E.; Park, Sung-Shim L.; Thompson, Elizabeth F.; Wilkens, Lynne R.; Patel, Yesha; Stram, Daniel O.; Le Marchand, Loic

2014-01-01

Nicotine metabolism influences smoking behavior and differences in metabolism probably contribute to ethnic variability in lung cancer risk. We report here on the proportion of nicotine metabolism by cytochrome P450 2A6-catalyzed C-oxidation, UDP-glucuronosyl transferase 2B10 (UGT2B10)-catalyzed N-glucuronidation and flavin monooxygenase 3-catalyzed N-oxidation in five ethnic/racial groups and the role of UGT2B10 genotype on the metabolic patterns observed. Nicotine and its metabolites were quantified in urine from African American (AA, n = 364), Native Hawaiian (NH, n = 311), White (n = 437), Latino (LA, n = 453) and Japanese American (JA, n = 674) smokers. Total nicotine equivalents, the sum of nicotine and six metabolites, and nicotine metabolism phenotypes were calculated. The relationship of UGT2B10 genotype to nicotine metabolic pathways was determined for each group; geometric means were computed and adjusted for age, sex, creatinine, and body mass index. Nicotine metabolism patterns were unique across the groups, C-oxidation was lowest in JA and NH (P < 0.0001), and N-glucuronidation lowest in AA (P < 0.0001). There was no difference in C-oxidation among Whites and AA and LA. Nicotine and cotinine glucuronide ratios were 2- and 3-fold lower in AA compared with Whites. Two UGT variants, a missense mutation (Asp67Tyr, rs61750900) and a splice variant (rs116294140) accounted for 33% of the variation in glucuronidation. In AA, the splice variant accounted for the majority of the reduced nicotine glucuronidation. UGT2B10 variant allele carriers had increased levels of C-oxidation (P = 0.0099). Our data indicate that the relative importance of nicotine metabolic pathways varies by ethnicity, and all pathways should be considered when characterizing the role of nicotine metabolism on smoking behavior and cancer risk. PMID:25233931

Interaction of FKBP5 with Childhood Adversity on Risk for Post-Traumatic Stress Disorder

PubMed Central

Xie, Pingxing; Kranzler, Henry R; Poling, James; Stein, Murray B; Anton, Raymond F; Farrer, Lindsay A; Gelernter, Joel

2010-01-01

FKBP5 regulates the cortisol-binding affinity and nuclear translocation of the glucocorticoid receptor. Polymorphisms at the FKBP5 locus have been associated with increased recurrence risk of depressive episodes and rapid response to antidepressant treatment. A recent study showed that FKBP5 genotypes moderated the risk of post-traumatic stress disorder (PTSD) symptoms associated with childhood maltreatment. One thousand one hundred forty-three European Americans (EAs) and 1284 African Americans (AAs) recruited for studies of the genetics of substance dependence were also screened for lifetime PTSD. Four single-nucleotide polymorphisms (SNPs) in FKBP5, rs3800373, rs9296158, rs1360780, and rs9470080, were genotyped on the complete sample. Logistic regression analyses were performed to explore the interactive effect of FKBP5 polymorphisms and childhood adversity on the risk for PTSD. After correction for multiple testing, childhood adversity significantly increased the risk for PTSD. FKBP5 genotypes were not associated with the development of the disorder. In AAs, one of the SNPs, rs9470080, moderated the risk of PTSD that was associated with childhood abuse. Without childhood adverse experiences, participants with the TT genotype of this SNP had the lowest risk for PTSD, whereas they had the highest risk for PTSD after childhood adversity exposure. In addition, in EAs, alcohol dependence was observed to interact with childhood adverse experiences, and also FKBP5 polymorphisms, to increase the risk for PTSD. This study provides further evidence of a gene × environment effect of FKBP5 and childhood abuse on the risk for PTSD in AAs. Further study is required in other populations. PMID:20393453

Influence of genetic variants of CYP2D6, CYP2C9, CYP2C19 and CYP3A4 on antiepileptic drug metabolism in pediatric patients with refractory epilepsy.

PubMed

López-García, Miguel A; Feria-Romero, Iris A; Serrano, Héctor; Rayo-Mares, Darío; Fagiolino, Pietro; Vázquez, Marta; Escamilla-Núñez, Consuelo; Grijalva, Israel; Escalante-Santiago, David; Orozco-Suarez, Sandra

2017-06-01

Identified the polymorphisms of CYP2D6, CYP2C9, CYP2C19 and CYP3A4, within a rigorously selected population of pediatric patients with drug-resistant epilepsy. The genomic DNA of 23 drug-resistant epilepsy patients and 7 patients with good responses were analyzed. Ten exons in these four genes were genotyped, and the drug concentrations in saliva and plasma were determined. The relevant SNPs with pharmacogenomics relations were CYP2D6*2 (rs16947) decreased your activity and CYP2D6*4 (rs1065852), CYP2C19*2 (rs4244285) and CYP3A4*1B (rs2740574) by association with poor metabolizer. The strongest risk factors were found in the AA genotype and allele of SNP rs3892097 from the CYP2D6 gene, followed by the alleles A and T of SNPs rs2740574 and rs2687116, respectively from CYP3A4. The most important concomitance was between homozygous genotype AA of rs3892097 and genotype AA of rs2740574 with 78.3% in drug-resistant epilepsy patients as compared to 14.3% in control patients. The results demonstrated the important role of the CYP 3A4*1B allelic variant as risk factor for developing drug resistance and CYP2D6, CYP2C19 SNPs and haplotypes may affect the response to antiepileptic drugs. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.

Ankle Bracing, Fatigue, and Time to Stabilization in Collegiate Volleyball Athletes

PubMed Central

Shaw, Megan Y; Gribble, Phillip A; Frye, Jamie L

2008-01-01

Context: Fatigue has been shown to disrupt dynamic stability in healthy volunteers. It is not known if wearing prophylactic ankle supports can improve dynamic stability in fatigued athletes. Objective: To determine the type of ankle brace that may be more effective at providing dynamic stability after a jump-landing task during normal and fatigued conditions. Design: Two separate repeated-measures analyses of variance with 2 within-subjects factors (condition and time) were performed for each dependent variable. Setting: Research laboratory. Patients or Other Participants: Ten healthy female collegiate volleyball athletes participated (age  =  19.5 ± 1.27 years, height  =  179.07 ± 7.6 cm, mass  =  69.86 ± 5.42 kg). Intervention(s): Athletes participated in 3 separate testing sessions, applying a different bracing condition at each session: no brace (NB), Swede-O Universal lace-up ankle brace (AB), and Active Ankle brace (AA). Three trials of a jump-landing task were performed under each condition before and after induced functional fatigue. The jump-landing task consisted of a single-leg landing onto a force plate from a height equivalent to 50% of each participant's maximal jump height and from a starting position 70 cm from the center of the force plate. Main Outcome Measure(s): Time to stabilization in the anterior-posterior (APTTS) and medial-lateral (MLTTS) directions. Results: For APTTS, a condition-by-time interaction existed (F2,18  =  5.55, P  =  .013). For the AA condition, Tukey post hoc testing revealed faster pretest (2.734 ± 0.331 seconds) APTTS than posttest (3.817 ± 0.263 seconds). Post hoc testing also revealed that the AB condition provided faster APTTS (2.492 ± 0.271 seconds) than AA (3.817 ± 0.263 seconds) and NB (3.341 ± 0.339 seconds) conditions during posttesting. No statistically significant findings were associated with MLTTS. Conclusions: Fatigue increased APTTS for the AA condition. Because the AB condition was more effective than the other 2 conditions during the posttesting, the AB appears to be the best option for providing dynamic stability in the anterior-posterior direction during a landing task. PMID:18345341

Influence of autoantibodies against AT1 receptor and AGTR1 polymorphisms on candesartan-based antihypertensive regimen: results from the study of optimal treatment in hypertensive patients with anti-AT1-receptor autoantibodies trial.

PubMed

Sun, Yanxiang; Liao, Yuhua; Yuan, Yong; Feng, Li; Ma, Shihui; Wei, Feng; Wang, Min; Zhu, Feng

2014-01-01

The autoantibodies against angiotensin AT1 receptors (AT1-AAs) in patients with essential hypertension exhibited an agonistic action like angiotensin II and maintained high blood pressure (BP). Angiotensin II receptor gene (AGTR1) polymorphisms were associated with BP response to RAS inhibition in the hypertensive population. Furthermore, the BP response to AT1 receptor blockers varied significantly among individuals with hypertension. We hypothesized that the polymorphisms of the AGTR1 and AT1-AAs might affect antihypertensive response to AT1 receptor blockers based in patients with primary hypertension. Patients who received a candesartan-based regimen came from the SOT-AT1 study (Study of Optimal Treatment in Hypertensive Patients with Anti-AT1-Receptor Autoantibodies). The established enzyme-labeled immunosorbent assay was used to detect AT1-AAs in the sera of the patients. Genotype 3 single nucleotide polymorphisms in AGTR1 gene was used by DNA sequencing. The correlations among AT1-AAs, AGTR1 gene polymorphisms or haplotypes, and the antihypertensive effect candesartan-based were analyzed using SPSS. The percentage of systolic BP reduction that was candesartan-based was greater in AT1-AA positive groups than in AT1-AA negative ones (21 ± 8 vs. 18 ± 9; P = .001). Meanwhile, systolic BP reduction that was candesartan-based was more significant in the group of rs5186 AC genotypes than AA homozygotes after adjusting for other confounding factors (37.55 ± 13.7 vs. 32.47 ± 17.27 mm Hg; adjusted P = .028). Furthermore, haplotypes (GCC) and (AAC) had impacts on the antihypertensive effect of candesartan therapy. The AT1-AAs, AGTR1 gene polymorphisms and haplotypes solely or jointly have influences on candesartan-based antihypertensive response in patients with primary hypertension. Copyright © 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Bovine GDF10 gene polymorphism analysis and its association with body measurement traits in Chinese indigenous cattle.

PubMed

Adoligbe, C; Zan, Linsen; Farougou, S; Wang, Hongbao; Ujjan, J A

2012-04-01

The objective of this research was to detect bovine GDF10 gene polymorphism and analyze its association with body measurement traits (BMT) of animals sampled from 6 different Chinese indigenous cattle populations. The populations included Xuelong (Xl), Luxi (Lx), Qinchuan (Qc), Jiaxian red (Jx), Xianang (Xn) and Nanyang (Ny). Blood samples were taken from a total of 417 female animals stratified into age categories of 12-36 months. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) was employed to find out GDF10 single polymorphism nucleotide (SNPs) and explore their possible association with BMT. Sequence analysis of GDF10 gene revealed 3 SNPs in total: 1 in exon1 (G142A) and 2 in exon3 (A11471G, and T12495C). G142A and T12495C SNPs are both synonymous mutation. They showed 2 genotypes namely respectively (GG, GA) and (PP and PB). A11471G SNP is a missense mutation leading to the change of Alanine to Threonine amino acid. It showed three genotypes namely AA, BB and AB. Analysis of association of polymorphism with body measurement traits at the three locus showed that there were significant effects on BMT in Qc, Jx and Ny cattle population. These results suggest that the GDF10 gene might have potential effects on body measurement traits in the above mentioned cattle populations and could be used for marker-assisted selection.

A novel cry2Ab gene from the indigenous isolate Bacillus thuringiensis subsp. kurstaki.

PubMed

Sevim, Ali; Eryüzlü, Emine; Demirbağ, Zihni; Demir, Ismail

2012-01-01

A novel cry2Ab gene was cloned and sequenced from the indigenous isolate of Bacillus thuringiensis subsp. kurstaki. This gene was designated as cry2Ab25 and its sequence revealed an open reading frame of 1,902 bp encoding a 633 aa protein with calculated molecular mass of 70 kDa and pI value of 8.98. The amino acid sequence of the Cry2Ab25 protein was compared with previously known Cry2Ab toxins, and the phylogenetic relationships among them were determined. The deduced amino acid sequence of the Cry2Ab25 protein showed 99% homology to the known Cry2Ab proteins, except for Cry2Ab10 and Cry2Ab12 with 97% homology, and a variation in one amino acid residue in comparison with all known Cry2Ab proteins. The cry2Ab25 gene was expressed in Escherichia coli BL21(DE3) cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed that the Cry2Ab25 protein is about 70 kDa. The toxin expressed in BL21(DE3) exhibited high toxicity against Malacosoma neustria and Rhagoletis cerasi with 73% and 75% mortality after 5 days of treatment, respectively.

Inheritance of Cry1F resistance, cross-resistance and frequency of resistant alleles in Spodoptera frugiperda (Lepidoptera: Noctuidae).

PubMed

Vélez, A M; Spencer, T A; Alves, A P; Moellenbeck, D; Meagher, R L; Chirakkal, H; Siegfried, B D

2013-12-01

Transgenic maize, Zea maize L., expressing the Cry1F protein from Bacillus thuringiensis has been registered for Spodoptera frugiperda (J. E. Smith) control since 2003. Unexpected damage to Cry1F maize was reported in 2006 in Puerto Rico and Cry1F resistance in S. frugiperda was documented. The inheritance of Cry1F resistance was characterized in a S. frugiperda resistant strain originating from Puerto Rico, which displayed >289-fold resistance to purified Cry1F. Concentration-response bioassays of reciprocal crosses of resistant and susceptible parental populations indicated that resistance is recessive and autosomal. Bioassays of the backcross of the F1 generation crossed with the resistant parental strain suggest that a single locus is responsible for resistance. In addition, cross-resistance to Cry1Aa, Cry1Ab, Cry1Ac, Cry1Ba, Cry2Aa and Vip3Aa was assessed in the Cry1F-resistant strain. There was no significant cross-resistance to Cry1Aa, Cry1Ba and Cry2Aa, although only limited effects were observed in the susceptible strain. Vip3Aa was highly effective against susceptible and resistant insects indicating no cross-resistance with Cry1F. In contrast, low levels of cross-resistance were observed for both Cry1Ab and Cry1Ac. Because the resistance is recessive and conferred by a single locus, an F1 screening assay was used to measure the frequency of Cry1F-resistant alleles from populations of Florida and Texas in 2010 and 2011. A total frequency of resistant alleles of 0.13 and 0.02 was found for Florida and Texas populations, respectively, indicating resistant alleles could be found in US populations, although there have been no reports of reduced efficacy of Cry1F-expressing plants.

Interleukin-10 -1082 G/A gene polymorphisms in Egyptian children with CAP

PubMed Central

Azab, Seham F.; Abdalhady, Mohamed A.; Elsaadany, Hosam F.; Elkomi, Mohamed A.; Elhindawy, Eman M.; Sarhan, Dina T.; Salam, Mohamed M.A.; Allah, Mayy A.N.; Emam, Ahmed A.; Noah, Maha A.; Abdelsalam, Nasser I.; Abdellatif, Sawsan H.; Rass, Anwar A.; Ismail, Sanaa M.; Gheith, Tarek; Aziz, Khalid A.; Hamed, Mohammed E.; Abdelrahman, Hind M.; Ahmed, Ahmed R.; Nabil, Rehab M.; Abdulmaksoud, Rehab S.; Yousef, Hala Y.

2016-01-01

Abstract Community-acquired pneumonia (CAP) is one of the leading causes of death worldwide. Cytokines are involved in the pathogenesis of CAP. To date, only a few studies concerned the association of interleukin-10 (IL-10) gene polymorphisms with CAP. In this study, we aimed to investigate whether the -1082(G/A) polymorphism in the promoter region of the IL-10 gene is involved in susceptibility to and the outcome of CAP, and we also measured the serum level of IL-10 to assess its relation to such polymorphism. This was a case–control study included 100 patients with CAP, and matched with age, gender, and ethnicity of 100 healthy control children. IL-10 -1082(G/A) gene polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism, while the serum IL-10 levels were measured by ELISA method. Compared to the controls subjects, the frequencies of the IL-10 -1082 AA genotype and A allele were observed to be overrepresented in patients with CAP (51%; odds ratio [OR] = 2.8; 95% confidence interval [CI]: 1.5–5.3 for the AA genotype; P < 0.01) and (70%; OR: 1.95; 95% CI: 1.27–3.00 for the A allele; P < 0.01, respectively). We found that patients with the GG genotype had significantly higher serum IL-10 levels (46.7 ± 9.5 pg/mL) compared to those with AG genotype (21.8 ± 4.5 pg/mL) and AA genotype (11.5 ± 3.3 pg/mL); P < 0.01, respectively. Our data revealed a significant positive association between the -1082 GG genotype and susceptibility to severe sepsis, acute respiratory failure, and hospital mortality (OR: 3.8; 95% CI: 1.3–11.2; P < 0.01). We demonstrate for the first time, to the best of our knowledge, that IL-10 -1082 (G/A) gene polymorphism may contribute to susceptibility to CAP in Egyptian children. Moreover, we observed that the presence of a G allele or GG genotype at the -1082 position of the promoter region of the IL-10 gene constitute risk factors for developing severe sepsis, acute respiratory failure, and hospital mortality among patients with CAP. PMID:27368016

Interleukin-10 -1082 G/A gene polymorphisms in Egyptian children with CAP: A case-control study.

PubMed

Azab, Seham F; Abdalhady, Mohamed A; Elsaadany, Hosam F; Elkomi, Mohamed A; Elhindawy, Eman M; Sarhan, Dina T; Salam, Mohamed M A; Allah, Mayy A N; Emam, Ahmed A; Noah, Maha A; Abdelsalam, Nasser I; Abdellatif, Sawsan H; Rass, Anwar A; Ismail, Sanaa M; Gheith, Tarek; Aziz, Khalid A; Hamed, Mohammed E; Abdelrahman, Hind M; Ahmed, Ahmed R; Nabil, Rehab M; Abdulmaksoud, Rehab S; Yousef, Hala Y

2016-06-01

Community-acquired pneumonia (CAP) is one of the leading causes of death worldwide. Cytokines are involved in the pathogenesis of CAP. To date, only a few studies concerned the association of interleukin-10 (IL-10) gene polymorphisms with CAP.In this study, we aimed to investigate whether the -1082(G/A) polymorphism in the promoter region of the IL-10 gene is involved in susceptibility to and the outcome of CAP, and we also measured the serum level of IL-10 to assess its relation to such polymorphism.This was a case-control study included 100 patients with CAP, and matched with age, gender, and ethnicity of 100 healthy control children. IL-10 -1082(G/A) gene polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism, while the serum IL-10 levels were measured by ELISA method.Compared to the controls subjects, the frequencies of the IL-10 -1082 AA genotype and A allele were observed to be overrepresented in patients with CAP (51%; odds ratio [OR] = 2.8; 95% confidence interval [CI]: 1.5-5.3 for the AA genotype; P < 0.01) and (70%; OR: 1.95; 95% CI: 1.27-3.00 for the A allele; P < 0.01, respectively). We found that patients with the GG genotype had significantly higher serum IL-10 levels (46.7 ± 9.5 pg/mL) compared to those with AG genotype (21.8 ± 4.5 pg/mL) and AA genotype (11.5 ± 3.3 pg/mL); P < 0.01, respectively. Our data revealed a significant positive association between the -1082 GG genotype and susceptibility to severe sepsis, acute respiratory failure, and hospital mortality (OR: 3.8; 95% CI: 1.3-11.2; P < 0.01).We demonstrate for the first time, to the best of our knowledge, that IL-10 -1082 (G/A) gene polymorphism may contribute to susceptibility to CAP in Egyptian children. Moreover, we observed that the presence of a G allele or GG genotype at the -1082 position of the promoter region of the IL-10 gene constitute risk factors for developing severe sepsis, acute respiratory failure, and hospital mortality among patients with CAP.

Juvenile idiopathic arthritis patients and their skeletal status: possible role of vitamin D receptor gene polymorphism.

PubMed

Kostik, M M; Smirnov, A M; Demin, G S; Scheplyagina, L A; Larionova, V I

2014-01-01

We evaluated bone mineralization and metabolism changes related to vitamin D receptor (VDR) polymorphic genotypes in children with juvenile idiopathic arthritis. One hundred and ninety eight children (82 boys and 116 girls) were included in our study. Bone mineral density (BMD) was measured by lumbar spine DXA. Osteocalcin, CTX, parathyroid hormone, total and ionized calcium, inorganic phosphate, total alkaline phosphatase activity was utilized for assessment of bone metabolism. Molecular testing: TaqI (rs731236) and Cdx2 (rs11568820) polymorphisms of VDR were detected by RFLP. No differences in TaqI and Cdx2 haplotypes, genotypes and alleles distribution related with normal and low BMD (Zscore <-2SD) were found. Children with low linear growth (<10th percentile) had more allele T-contained genotypes of TagI VDR (p = 0.037), compare with medium or high linear growth children. Children with high linear growth (>90th percentile) had the highest frequency of allele A-contained genotypes (GA+AA) of Cdx2 VDR (p = 0.009). Girls with TT TaqI VDR, who never been treated by glucocorticoides had lower BMD-Zscore than C allele carriers (TT = -0.94SD [IQR: -2.1;-0.5], TC+CC = -0.62SD [IQR: -1.26;0.39], p = 0.03). Girls with Tanner I with TT had higher total and ionized Ca level than carriers of C allele (Ca: TT = 2.43 ± 0.15 mmol/l, TC+CC = 2.28 ± 0.2 mmol/l, p = 0.024; Ca(2+): TT = 1.15 ± 0.08 mmol/l, TC+CC = 1.06 ± 0.13 mmol/l, p = 0.026). Presence of TT genotype negatively correlated with BMD-Zscore (r = -0.28, p = 0.04), and positively with frequency of LBMD (r = 0.3, p = 0.037). Boy with GG Cdx2 genotype had lower total Ca (GG = 2.3 ± 0.17 mmol/l, GA+AA = 2.43 ± 0.17 mmol/l, p = 0.004) compare with carriers of A allele. Pubertal boys (Tanner IV-V) with GG had higher CTX (GG = 1.75 ± 0.11 ng/ml, GA+AA = 1.06 ± 0.07 ng/ml, p = 0.04. TT genotype of TaqI and GG genotype of Cdx2 VDR is a negative factor impact bone mineralization metabolism and linear growth.

46 CFR 107.305 - Plans and information.

Code of Federal Regulations, 2013 CFR

2013-10-01

... systems. Marine Engineering (z) Plans required for marine engineering equipment and systems by Subchapter F of this chapter. Electrical Engineering (aa) Plans required for electrical engineering equipment... materials that do not conform to ABS or ASTM specifications, complete specifications, including chemical and...

FTO rs9939609 Does Not Interact with Physical Exercise but Influences Basal Insulin Metabolism in Brazilian Overweight and Obese Adolescents

PubMed Central

Leite, Neiva; Furtado-Alle, Lupe; Teixeira, Mayza Dalcin; de Souza, Ricardo Lehtonen Rodrigues; da Silva, Larissa Rosa; Pizzi, Juliana; Lopes, Maria de Fátima Aguiar; Titski, Ana Cláudia Kapp

2018-01-01

Purpose The rs9939609 SNP (T > A) in FTO gene is associated with obesity and type 2 diabetes. The present study aimed at verifying whether this SNP influenced biochemical outcomes of children and adolescents who are overweight/obese submitted to a program of physical exercise and also if there was influence on basal levels of these biochemical variables. Methods The sample was composed by 432 children and adolescents grouped in three ways (obese, overweight, and normal weight); of these, 135 children and adoloescents who are obese and overweight were submitted to a physical exercise program for 12 weeks. All were genotyped by TaqMan SNP genotyping assay. Results The children and adolescents who are overweight/obese and carriers of AA genotype had higher levels of insulin (p=0.03) and HOMA (p=0.007) and lower levels of glucose (p=0.003), but the SNP did not modulate the response to physical exercise. Conclusions In our study, the rs9939609 AA genotype was associated with parameters related to insulin metabolism but did not interact with physical exercise. PMID:29854435

The CYP1A2 -163C>A polymorphism does not alter the effects of caffeine on basketball performance.

PubMed

Puente, Carlos; Abián-Vicén, Javier; Del Coso, Juan; Lara, Beatriz; Salinero, Juan José

2018-01-01

The aim of this investigation was to analyze the influence of the genetic variations of the -163C>A polymorphism of the CYP1A2 gene on the ergogenic effects of caffeine in elite basketball players. Nineteen elite basketball players (10 men and 9 women) ingested 3 mg⋅kg-1 of caffeine or a placebo 60 min before performing 10 repetitions of the following series: the Abalakov jump test followed by the Change-of-Direction and Acceleration Test (CODAT). The players then competed in a 20-min simulated basketball game. Self-perceived performance and side effects were recorded by questionnaires after the trials. The effects of caffeine on basketball performance were established according to players' CYP1A2 genotype (rs762551): AA homozygotes (n = 10) and C-allele carriers (n = 9). In the 10 repetitions, caffeine increased Abalakov jump height by a mean of 2.9±3.6% in AA homozygotes (p = 0.03) while this effect did not reach statistical significance for C-allele carriers (2.3 ± 6.8%; p = 0.33). Caffeine did not affect sprint time in the CODAT test in either genotype group but it increased the number of impacts performed during the simulated game in both AA homozygotes (4.1 ± 5.3%; p = 0.02) and C-allele carriers (3.3 ± 3.2%; p = 0.01). During the 24 h following the test, AA homozygotes tended to experience increased insomnia with caffeine while C-allele carriers did not present this effect. The remaining variables were unaffected by the genotype. The CYP1A2 -163C>A polymorphism minimally altered the ergogenicity derived from the consumption of a moderate dose of caffeine in elite basketball players.

Comprehensive evaluation of the Estrogen Receptor Alpha gene reveals further evidence for association with type 2 diabetes enriched for nephropathy in an African American population

PubMed Central

Keene, Keith L.; Mychaleckyj, Josyf C.; Smith, Shelly G.; Leak, Tennille S.; Perlegas, Peter S.; Langefeld, Carl D.; Herrington, David M.; Freedman, Barry I.; Rich, Stephen S.; Bowden, Donald W.; Sale, Michèle M.

2009-01-01

We previously investigated the estrogen receptor α gene (ESR1) as a positional candidate for type 2 diabetes (T2DM), and found evidence for association between the intron 1-intron 2 region of this gene and type 2 diabetes and/or nephropathy in an African American (AA) population. Our objective was to comprehensively evaluate variants across the entire ESR1 gene for association in AA with T2DM and End Stage Renal Disease (T2DM-ESRD). One hundred fifty SNPs in ESR1, spanning 476 kb, were genotyped in 577 AA individuals with T2DM-ESRD and 596 AA controls. Genotypic association tests for dominant, additive, and recessive models, and haplotypic association, were calculated using a χ2 statistic and corresponding P value. Thirty-one SNPs showed nominal evidence for association (P< 0.05) with T2DM-ESRD in one or more genotypic model. After correcting for multiple tests, promoter SNP rs11964281 (nominal P=0.000291, adjusted P=0.0289), and intron 4 SNPs rs1569788 (nominal P=0.000754, adjusted P=0.0278) and rs9340969 (nominal P=0.00109, adjusted P=0.0467) remained significant at experimentwise error rate (EER) P<0.05 for the dominant class of tests. Twenty-three of the thirty-one associated SNPs cluster within the intron 4-intron 6 region. Gender stratification revealed nominal evidence for association with 35 SNPs in females (352 cases; 306 controls) and seven SNPs in males (225 cases; 290 controls). We have identified a novel region of the ESR1 gene that may contain important functional polymorphisms in relation to susceptibility to T2DM and/or diabetic nephropathy. PMID:18305958

Comprehensive evaluation of the estrogen receptor alpha gene reveals further evidence for association with type 2 diabetes enriched for nephropathy in an African American population.

PubMed

Keene, Keith L; Mychaleckyj, Josyf C; Smith, Shelly G; Leak, Tennille S; Perlegas, Peter S; Langefeld, Carl D; Herrington, David M; Freedman, Barry I; Rich, Stephen S; Bowden, Donald W; Sale, Michèle M

2008-05-01

We previously investigated the estrogen receptor alpha gene (ESR1) as a positional candidate for type 2 diabetes (T2DM), and found evidence for association between the intron 1-intron 2 region of this gene and T2DM and/or nephropathy in an African American (AA) population. Our objective was to comprehensively evaluate variants across the entire ESR1 gene for association in AA with T2DM and end stage renal disease (T2DM-ESRD). One hundred fifty SNPs in ESR1, spanning 476 kb, were genotyped in 577 AA individuals with T2DM-ESRD and 596 AA controls. Genotypic association tests for dominant, additive, and recessive models, and haplotypic association, were calculated using a chi(2) statistic and corresponding P value. Thirty-one SNPs showed nominal evidence for association (P < 0.05) with T2DM-ESRD in one or more genotypic model. After correcting for multiple tests, promoter SNP rs11964281 (nominal P = 0.000291, adjusted P = 0.0289), and intron 4 SNPs rs1569788 (nominal P = 0.000754, adjusted P = 0.0278) and rs9340969 (nominal P = 0.00109, adjusted P = 0.0467) remained significant at experimentwise error rate (EER) P

The ABCG2 gene Q141K polymorphism contributes to an increased risk of gout: a meta-analysis of 2185 cases.

PubMed

Qiu, Ya; Liu, Hua; Qing, Yufeng; Yang, Min; Tan, Xiaoyao; Zhao, Mingcai; Lin, Monica; Zhou, Jingguo

2014-09-01

Individual genetic association studies examining the relationship between the ABCG2 gene polymorphisms and gout have yielded inconsistent results. This study aims to evaluate the association between the ABCG2 gene variants and gout using meta-analysis. Relevant studies were identified by searching databases extensively. The odds ratio (OR) was calculated using a random-effect or fixed-effect model. A Q statistic was used to evaluate homogeneity, and Egger's test and funnel plot were used to assess publication bias. Subgroup analyses on ethnicities and sex were also performed. A total of 7 studies, including 2185 gout patients and 8028 controls from 5 countries or regions, were included and identified for the current meta-analysis. It was found that the A allele or AA genotype of the ABCG2 Q141K polymorphism (rs2231142) had an increased risk of gout in the general population (A allele, p < 0.00001 and AA genotype, p < 0.00001, respectively). On the contrary, CC homozygote played a protective role against the risk of gout (p < 0.00001). Similar results were found in subgroup analyses. However, there was a significant heterogeneity among studies. Existing evidence indicates that the Q141K polymorphism (rs2231142, the A allele and AA genotype) is associated with an increased risk of gout.

Pregnancy-associated plasma protein A gene polymorphism in pregnant women with preeclampsia and intrauterine growth restriction.

PubMed

Ozkan, Sultan; Sanhal, Cem Yasar; Yeniel, Ozgur; Arslan Ates, Esra; Ergenoglu, Mete; Bınbır, Birol; Onay, Huseyin; Ozkınay, Ferda; Sagol, Sermet

2015-10-01

Preeclampsia (PE) and intrauterine growth restriction (IUGR) are still among the most commonly researched titles in perinatology. To shed light on their etiology, new prevention and treatment strategies are the major targets of studies. In this study, we aimed to investigate the relation between gene polymorphism of one of the products of trophoblasts, pregnancy-associated plasma protein A (PAPP-A) and PE/IUGR.A total of 147 women (IUGR, n = 61; PE, n = 47; IUGR + PE, n = 37; eclampsia, n = 2) were compared with 103 controls with respect to the sequencing of exon 14 of the PAPP-A gene to detect (rs7020782) polymorphism. Genotypes "AA" and "CC" were given in the event of A or C allele homozygosity and "AC" in A and C allele heterozygosity. Our findings revealed that the rate of AA, CC homozygotes, and AC heterozygotes did not differ between groups. Moreover, there was no difference in the distribution of PAPP-A genotypes among the patients with IUGR, PE, IUGR + PE, or eclampsia. Finally, birth weight, rate of the presence of proteinuria, and total protein excretion on 24-hour urine were similar in the subgroups of AA, AC, and CC genotypes in the study group. Our study demonstrated no association between PAPP-A gene rs7020782 polymorphism and PE/IUGR. Copyright © 2015. Published by Elsevier Taiwan.

Binding specificity of Bacillus thuringiensis Cry1Aa for purified, native Bombyx mori aminopeptidase N and cadherin-like receptors

PubMed Central

Jenkins, Jeremy L; Dean, Donald H

2001-01-01

Background To better understand the molecular interactions of Bt toxins with non-target insects, we have examined the real-time binding specificity and affinity of Cry1 toxins to native silkworm (Bombyx mori) midgut receptors. Previous studies on B. mori receptors utilized brush border membrane vesicles or purifed receptors in blot-type assays. Results The Bombyx mori (silkworm) aminopeptidase N (APN) and cadherin-like receptors for Bacillus thuringiensis insecticidal Cry1Aa toxin were purified and their real-time binding affinities for Cry toxins were examined by surface plasmon resonance. Cry1Ab and Cry1Ac toxins did not bind to the immobilized native receptors, correlating with their low toxicities. Cry1Aa displayed moderate affinity for B. mori APN (75 nM), and unusually tight binding to the cadherin-like receptor (2.6 nM), which results from slow dissociation rates. The binding of a hybrid toxin (Aa/Aa/Ac) was identical to Cry1Aa. Conclusions These results indicate domain II of Cry1Aa is essential for binding to native B. mori receptors and for toxicity. Moreover, the high-affinity binding of Cry1Aa to native cadherin-like receptor emphasizes the importance of this receptor class for Bt toxin research. PMID:11722800

Variants of endothelial nitric oxide synthase gene are associated with components of metabolic syndrome in an Arab population.

PubMed

Alkharfy, Khalid M; Al-Daghri, Nasser M; Al-Attas, Omar S; Alokail, Majed S; Mohammed, Abdul Khader; Vinodson, Benjamin; Clerici, Mario; Kazmi, Usamah; Hussain, Tajamul; Draz, Hossam M

2012-01-01

Genetics plays a crucial role in the development of metabolic syndrome (MetS). Here we examined the association between endothelial nitric oxide synthase (eNOS) gene polymorphisms and MetS in a Saudi Arabian cohort to extend the understanding of the genetic basis of MetS in diverse ethnic populations. Anthropometric, clinical and biochemical parameters as well as genotyping for 894G>T, -786T>C variants of eNOS gene by PCR-RFLP and 4a/b by direct PCR were performed in 886 Saudi Arabians (477 MetS and 409 Non-MetS). The genotype distribution (TT, p=0.001; TC, p=0.001; TC+CC, p=0.001) and allele (T, p=0.007; C, p=0.007) frequency of the -786T>C SNP were significantly different between Non-MetS and MetS subjects which remained significant after Bonferroni correction. Moreover: 1) the GT and GT+TT genotypes of the 894G>T SNP were associated with elevated blood pressure (p=0.017, and p=0.022, respectively); 2) the ab variant of 4a/b polymorphism was associated with decreased HDL levels (p= 0.044); and 3) the TC+CC genotype and C allele of the -786T>C SNP were associated with increased fasting glucose levels (p=0.039, and p=0.028, respectively). Also, G-a-C was identified as the risk haplotype for MetS susceptibility (p=0.034). The results suggest a significant association of 894G>T, 4a/b and -786T>C polymorphisms with MetS and its components is present in an Arab population. A genetic predisposition to develop abnormal metabolic phenotypes, consistent with an increased prevalence of metabolic phenotypes can be detected in this ethnic group.

Novel single nucleotide polymorphisms of the bovine methyltransferase 3b gene and their association with meat quality traits in beef cattle.

PubMed

Liu, X; Guo, X Y; Xu, X Z; Wu, M; Zhang, X; Li, Q; Ma, P P; Zhang, Y; Wang, C Y; Geng, F J; Qin, C H; Liu, L; Shi, W H; Wang, Y C; Yu, Y

2012-08-16

DNA methylation is essential for adipose deposition in mammals. We screened SNPs of the bovine DNA methyltransferase 3b (DNMT3b) gene in Snow Dragon beef, a commercial beef cattle population in China. Nine SNPs were found in the population and three of six novel SNPs were chosen for genotyping and analyzing a possible association with 16 meat quality traits. The frequencies of the alleles and genotypes of the three SNPs in Snow Dragon beef were similar to those in their terminal-paternal breed, Wagyu. Association analysis disclosed that SNP1 was not associated with any of the traits; SNP2 was significantly associated with lean meat color score and chuck short rib score, and SNP3 had a significant effect on dressing percentage and back-fat thickness in the beef population. The individuals with genotype GG for SNP2 had a 25.7% increase in lean meat color score and a 146% increase in chuck short rib score, compared with genotype AA. The cattle with genotype AG for SNP3 had 35.7 and 24% increases in dressing percentage and 28.8 and 29.2% increases in back-fat thickness, compared with genotypes GG and AA, respectively. Genotypic combination analysis revealed significant interactions between SNP1 and SNP2 and between SNP2 and SNP3 for the traits rib-eye area and live weight. We conclude that there is considerable evidence that DNMT3b is a determiner of beef quality traits.

Effect of genetic polymorphism of UCP2-866 G/A on repaglinide response in Chinese patients with type 2 diabetes.

PubMed

Wang, Shan; Se, Yan-Mei; Liu, Zhao-Qian; Lei, Ming-Xiang; Hao-BoYang; Sun, Zhi-Xiang; Nie, Sheng-Dan; Zeng, Xiao-min; Wu, Jing

2012-01-01

The aim of the present study was to evaluate the impact of the UCP2-866 G/A polymorphism on the efficacy of repaglinide in treating patients with diabetes mellitus type 2 (T2DM). 370 patients with T2DM and 166 healthy volunteers were enrolled to identify UCP2-866 G/A genotypes. 16 patients with GG genotype, 14 with GA genotype and 11 with AA genotype of UCP2-866 G/A underwent an 8-week repaglinide treatment regimen. There were no differences in allele frequency of UCP2-866 G/A between T2DM patients and control subjects. The patient with AA genotype of UCP2-866 G/A had higher levels of fasting plasma glucose (FPG), 30-min and 2-h postload plasma glucose, glycated haemoglobin (HbA1c), and lower concentrations of 30-min and 2-h postload plasma insulin, homeostasis model assessment of beta cell function (HOMA-beta), deltaI30/deltaG30 compared with GG genotype. After repaglinide treatment for 8 consecutive weeks, we found that A allele carriers of UCP2 in the T2DM patients had smaller decrease in FPG (P < 0.05) and HbA1c (P < 0.05), and smaller increase in 30-min postload plasma insulin (P < 0.01) compared with GG genotypes. We demonstrated that UCP2-866 G/A polymorphism is associated with the therapeutic efficacy of repaglinide in Chinese T2DM patients.

Characterization of hepatitis B virus surface antigen variability and impact on HBs antigen clearance under nucleos(t)ide analogue therapy.

PubMed

Velay, A; Jeulin, H; Eschlimann, M; Malvé, B; Goehringer, F; Bensenane, M; Frippiat, J-P; Abraham, P; Ismail, A M; Murray, J M; Combet, C; Zoulim, F; Bronowicki, J-P; Schvoerer, E

2016-05-01

For hepatitis B virus (HBV)-related chronic infection under treatment by nucleos(t)ide analogues (NUCs), HBsAg clearance is the ultimate therapeutic goal but very infrequent. We investigated how HBV envelope protein variability could lead to differential HBsAg clearance on NUCs. For 12 HBV genotype D patients receiving NUCs, six resolvers (HBsAg clearance) were compared to six matched nonresolvers (HBsAg persistence). PreS/S amino acid (aa) sequences were analysed with bioinformatics to predict HBV envelope antigenicity and aa covariance. To enrich our analyses on very rare resolvers, these were compared with other HBV genotype D strains in three characterized clinical cohorts including common chronically infected patients. The sT125M+sP127T combination was observed in four nonresolvers of six, corroborated by aa covariance analysis, associated with a lower predicted antigenicity than sT125T+sP127P. Concordant features within this HBV key functional domain, at positions 125 and 127, were reported from two of the three comparative cohorts. In our hands, a lower ELISA reactivity of HBV-vaccinated mice sera was observed against the sT125M mutant. In the S gene, 56 aa changes in minor variants were detected in non-resolvers, mainly in the major hydrophilic region, vs 28 aa changes in resolvers. Molecular features in patients showing HBsAg persistence on NUCs argue in favour of a different aa pattern in the HBV S gene compared to those showing HBsAg clearance. In nonresolvers, a decrease in HBs 'a' determinant antigenicity and more frequent mutations in the S gene suggest a role for the HBV envelope characteristics in HBsAg persistence. © 2016 John Wiley & Sons Ltd.

Genetic polymorphism and prostate cancer aggressiveness: a case-only study of 1,536 GWAS and candidate SNPs in African-Americans and European-Americans.

PubMed

Bensen, Jeannette T; Xu, Zongli; Smith, Gary J; Mohler, James L; Fontham, Elizabeth T H; Taylor, Jack A

2013-01-01

Genome-wide association studies have established a number of replicated single nucleotide polymorphisms (SNPs) for susceptibility to prostate cancer (CaP), but it is unclear whether these susceptibility SNPs are also associated with disease aggressiveness. This study evaluates whether such replication SNPs or other candidate SNPs are associated with CaP aggressiveness in African-American (AA) and European-American (EA) men. A 1,536 SNP panel which included 34 genome-wide association study (GWAS) replication SNPs, 38 flanking SNPs, a set of ancestry informative markers, and SNPs in candidate genes and other areas was genotyped in 1,060 AA and 1,087 EA men with incident CaP from the North Carolina-Louisiana Prostate Cancer Project (PCaP). Tests for association were conducted using ordinal logistic regression with a log-additive genotype model and a 3-category CaP aggressiveness variable. Four GWAS replication SNPs (rs2660753, rs13254738, rs10090154, rs2735839) and seven flanking SNPs were associated with CaP aggressiveness (P < 0.05) in three genomic regions: One at 3p12 (EA), seven at 8q24 (5 AA, 2 EA), and three at 19q13 at the kallilkrein-related peptidase 3 (KLK3) locus (two AA, one AA and EA). The KLK3 SNPs also were associated with serum prostate-specific antigen (PSA) levels in AA (P < 0.001) but not in EA. A number of the other SNPs showed some evidence of association but none met study-wide significance levels after adjusting for multiple comparisons. Some replicated GWAS susceptibility SNPs may play a role in CaP aggressiveness. However, like susceptibility, these associations are not consistent between racial groups. Copyright © 2012 Wiley Periodicals, Inc.

Genetic polymorphism and prostate cancer aggressiveness: A case-only study of 1536 GWAS and candidate SNPs in African Americans and European Americans

PubMed Central

Bensen, Jeannette T.; Xu, Zongli; Smith, Gary J.; Mohler, James L.; Fontham, Elizabeth T.H.; Taylor, Jack A.

2012-01-01

BACKGROUND Genome-wide association studies have established a number of replicated single nucleotide polymorphisms (SNPs) for susceptibility to prostate cancer (CaP), but it is unclear whether these susceptibility SNPs are also associated with disease aggressiveness. This study evaluates whether such replication SNPs or other candidate SNPs are associated with CaP aggressiveness in African-American (AA) and European-American (EA) men. METHODS A 1,536 SNP panel which included 34 genome-wide association study (GWAS) replication SNPs, 38 flanking SNPs, a set of ancestry informative markers, and SNPs in candidate genes and other areas was genotyped in 1,060 AA and 1,087 EA men with incident CaP from the North Carolina-Louisiana Prostate Cancer Project (PCaP). Tests for association were conducted using ordinal logistic regression with a log-additive genotype model and a 3-category CaP aggressiveness variable. RESULTS 4 GWAS replication SNPs (rs2660753, rs13254738, rs10090154, rs2735839) and 7 flanking SNPs were associated with CaP aggressiveness (P<0.05) in 3 genomic regions: one at 3p12 (EA), 7 at 8q24 (5 AA, 2 EA), and 3 at 19q13 at the kallilkrein-related peptidase 3 (KLK3) locus (2 AA, 1 AA and EA). The KLK3 SNPs also were associated with serum prostate-specific antigen (PSA) levels in AA (p < 0.001) but not in EA. A number of the other SNPs showed some evidence of association but none met study-wide significance levels after adjusting for multiple comparisons. CONCLUSIONS Some replicated GWAS susceptibility SNPs may play a role in CaP aggressiveness. However, like susceptibility, these associations are not consistent between racial groups. PMID:22549899

Influence of host interleukin-10 polymorphisms on development of traveler's diarrhea due to heat-labile enterotoxin-producing Escherichia coli in travelers from the United States who are visiting Mexico.

PubMed

Flores, Jose; DuPont, Herbert L; Lee, Stephanie A; Belkind-Gerson, Jaime; Paredes, Mercedes; Mohamed, Jamal A; Armitige, Lisa Y; Guo, Dong-Chuan; Okhuysen, Pablo C

2008-08-01

Up to 60% of U.S. visitors to Mexico develop traveler's diarrhea (TD), mostly due to enterotoxigenic Escherichia coli (ETEC) strains that produce heat-labile (LT) and/or heat-stable (ST) enterotoxins. Distinct single-nucleotide polymorphisms (SNPs) within the interleukin-10 (IL-10) promoter have been associated with high, intermediate, or low production of IL-10. We conducted a prospective study to investigate the association of SNPs in the IL-10 promoter and the occurrence of TD in ETEC LT-exposed travelers. Sera from U.S. travelers to Mexico collected on arrival and departure were studied for ETEC LT seroconversion by using cholera toxin as the antigen. Pyrosequencing was performed to genotype IL-10 SNPs. Stools from subjects who developed diarrhea were also studied for other enteropathogens. One hundred twenty-one of 569 (21.3%) travelers seroconverted to ETEC LT, and among them 75 (62%) developed diarrhea. Symptomatic seroconversion was more commonly seen in subjects who carried a genotype producing high levels of IL-10; it was seen in 83% of subjects with the GG genotype versus 54% of subjects with the AA genotype at IL-10 gene position -1082 (P, 0.02), in 71% of those with the CC genotype versus 33% of those with the TT genotype at position -819 (P, 0.005), and in 71% of those with the CC genotype versus 38% of those with the AA genotype at position -592 (P, 0.02). Travelers with the GCC haplotype were more likely to have symptomatic seroconversion than those with the ATA haplotype (71% versus 38%; P, 0.002). Travelers genetically predisposed to produce high levels of IL-10 were more likely to experience symptomatic ETEC TD.

The genetic polymorphism and expression profiles of NLRP3 inflammasome in patients with chronic myeloid leukemia.

PubMed

Zhang, Amin; Yu, Jie; Yan, Shuxin; Zhao, Xia; Chen, Chen; Zhou, Ying; Zhao, Xueyun; Hua, Mingqiang; Wang, Ruiqing; Zhang, Chen; Zhong, Chaoqin; He, Na; Ji, Chunyan; Ma, Daoxin

2018-01-01

NLRP3 inflammasome has been recently reported as an important risk factor in the development of cancer. But the relationship between polymorphisms of NLRP3 inflammasome related genes and chronic myeloid leukemia (CML) is rarely reported. Therefore, the aim of the present study was to investigate the association of five genetic polymorphisms (NLRP3, IL-1β, IL-18, CARD8 and NF-κB) in 267 CML patients and 344 healthy controls. We found that the AT genotype of CARD8 (rs2043211) was significantly higher compared to TT genotype in high and intermediate risk CML patients. IL-1β (rs16944) polymorphism in early molecular response at 6 months was marginally different, with more GG and less AA genotype in BCR-ABL IS >1% group. IL-18 (rs1946518) polymorphism was significantly different with more GG genotype in BCR-ABL IS >1% group at 6 months. We also demonstrated that WBC count of newly diagnosed patients carrying AG genotype was significantly higher than that of GG or AA genotype of IL-1β (rs16944). The onset age of patients carrying ins/ins genotype of NF-κB (rs28362491) was significantly older than that of ins/del and del/del genotype. Moreover, IL-1β or NLRP3 mRNA expression was decreased and IL-18 mRNA expression was increased significantly in CML patients compared with controls. In conclusion, the genetic polymorphisms of NLRP3 inflammasome may be served as potential predictors for CML. Copyright © 2017 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Public Health Emergency Management Within the Department of Defense

DTIC Science & Technology

2010-03-05

February 20071 (aa) DoD Instruction 1100.21, “ Voluntary Services in the Department of Defense,” March 11, 2002 (ab) DoD Instruction 5210.25...include eradication of disease, identification of affected animals, animal quarantine implementation, euthanasia , carcass disposal, cleaning and

75 FR 4474 - Energy Conservation Program: Certification, Compliance, and Enforcement Requirements for Certain...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-28

... titled ``Certification, Compliance, and Enforcement Requirements for Certain Consumer Products and...-AA96 and 1904-AB53 Energy Conservation Program: Certification, Compliance, and Enforcement Requirements for Certain Consumer Products and Commercial and Industrial Equipment; Correction AGENCY: Office of...

In-vitro microbial production of conjugated linoleic acid by probiotic L. plantarum strains: Utilization as a functional starter culture in sucuk fermentation.

PubMed

Özer, Cem O; Kılıç, Birol; Kılıç, Gülden Başyiğit

2016-04-01

Twenty-three probiotic Lactobacillus plantarum strains were screened in-vitro to determine their ability to produce conjugated linoleic acid (CLA). L. plantarum AA1-2 and L. plantarum AB20-961 were identified as potential strains for CLA production. Optimum conditions for these strains to produce high levels of CLA were determined by evaluating the amount of added hydrolyzed sunflower oil (HSO) and initial pH levels in a nutrient medium. The highest CLA production was obtained in medium with pH6.0 and 2% HSO (P<0.05). Those strains were then used as starter culture in sucuk fermentation. Five sucuk treatments included a control (no starter culture), two sucuk groups with L. plantarum AA1-2 at the initial pH of 5.8 or 6.0 and two sucuk groups with L. plantarum AB20-961 at the initial pH of 5.8 or 6.0. Results indicate that L. plantarum AB20-961 produced higher amount of CLA in sucuk at initial pH of 5.8 and 6.0 levels during first 24h of fermentation compared with other groups. CLA isomer concentration decreased in all sucuk groups during the rest of the fermentation period (P<0.05) and remained quite stable during the storage. This study demonstrated that probiotic L. plantarum AB20-961 can be used in sucuk manufacturing without posing any quality problems. Copyright © 2015 Elsevier Ltd. All rights reserved.

Near-Infrared Imaging Polarimetry of Inner Region of GG Tau A Disk

NASA Technical Reports Server (NTRS)

Yang, Yi; Hashimoto, Jun; Hayashi, Saeko S.; Tamura, Motohide; Mayama, Satoshi; Rafikov, Roman; Akiyama, Eiji; Carson, Joseph C.; Janson, Markus; Kwon, Jungmi;

Edge functionalised & Li-intercalated 555-777 defective bilayer graphene for the adsorption of CO2 and H2O

NASA Astrophysics Data System (ADS)

Lalitha, Murugan; Lakshmipathi, Senthilkumar; Bhatia, Suresh K.

2017-04-01

The adsorption of CO2 and H2O on divacanacy (DV) defected graphene cluster, and its bilayer counterpart is investigated using first-principles calculations. Both single and bilayer DV graphene cluster, are functionalised with H and F atoms. On these sheets the gas molecules are physisorbed, and the divacancy defect effectively improves the adsorption of CO2, while fluorination enhances the hydrophobicity of the graphene cluster. Among the convex and concave curvature regions induced due to the DV defect, the adsorption of the gas molecules on the concave meniscus is more favourable. Fluorine termination induces 73% reduction in Henry law constants for H2O, while for the CO2 molecule it increases by 8%, which indicates the DV defective sheet is a better candidate for CO2 capture compared to the STW defective sheet. Besides, both AA and AB divacant defect bilayer sheets are equally stable, wherein AA stacking results in a cavity between the sheets, while in AB stacking, the layers slide one over the other. Nevertheless, both these bilayer sheets are comparatively stabler than the monolayer. However, intercalation of lithium decreases the interlayer separation, particularly in AA stacking, which enhances the CO2 adsorption, but in the Bernal stacking enhances it hydrophobicity.

Analysis of interleukin-10 gene polymorphisms in patients with chronic periodontitis and healthy controls

PubMed Central

Moudi, Bita; Heidari, Zahra; Mahmoudzadeh-Sagheb, Hamidreza; Moudi, Mehrnoosh

2018-01-01

Background: Interleukin-10 (IL-10) is an anti-inflammatory cytokine that has important roles in the periodontal diseases. The IL10-1082, -819, and -592 polymorphisms in the promoter region of IL-10 gene have been associated with various IL-10 expressions. The aim of this study was to investigate the association between these gene polymorphisms with chronic periodontitis in a sample of Iranian populations from Southeast of Iran. Materials and Methods: IL-10 single nucleotide polymorphisms were analyzed in 210 patients with chronic periodontitis (CP) and 100 individuals without CP by polymerase chain reaction-restriction fragment length polymorphism method. Statistical analysis of data was performed using the Chi-square test. The risk associated with single alleles, genotypes, and haplotypes were calculated by performing a multiple logistic regression analysis to estimate the odds ratio (OR) and 95% confidence interval (CI). P < 0.05 for statistical significance. Results: The prevalences of AG and GG genotypes of IL10-1082 were significantly different between CP and control groups in comparison to AA genotype (OR = 2.671; CI = 1.482–4.815; P = 0.001 for AG vs. AA, OR = 4.151; CI = 2.128–8.097; P < 0.001 for GG vs. AA). In addition, subjects with at least one IL10-1082-G allele were significantly had an increased risk for CP (OR = 2.157; CI = 1.531–3.038; P < 0.001). The distribution of the IL10-819 and IL10-592 genotypes was not different between CP and control subjects (P = 0.109 and P = 0.139, respectively). The combination of different genotypes showed that GCC haplotype was significantly different between groups (OR = 4.379; CI = 1.077–17.807; P = 0.039). Conclusion: The results demonstrated that IL10-1082 polymorphism was a putative risk factor for chronic periodontitis and associated with increased susceptibility to CP. PMID:29497450

Association of a variant in the regulatory region of NADPH oxidase 4 gene and metabolic syndrome in patients with chronic hepatitis C.

PubMed

Siqueira, Erika Rabelo Forte de; Pereira, Luciano Beltrao; Stefano, Jose Tadeu; Patente, Thiago; Cavaleiro, Ana Mercedes; Silva Vasconcelos, Luydson Richardson; Carmo, Rodrigo Feliciano; Moreira Beltrao Pereira, Leila Maria; Carrilho, Flair Jose; Corrêa-Giannella, Maria Lucia; Oliveira, Claudia P

2015-03-28

Given the important contribution of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system to the generation of reactive oxygen species induced by hepatitis C virus (HCV), we investigated two single nucleotide polymorphisms (SNPs) in the putative regulatory region of the genes encoding NADPH oxidase 4 catalytic subunit (NOX4) and its regulatory subunit p22phox (CYBA) and their relation with metabolic and histological variables in patients with HCV. One hundred seventy eight naïve HCV patients (49.3% male; 65% HCV genotype 1) with positive HCV RNA were genotyped using specific primers and fluorescent-labeled probes for SNPs rs3017887 in NOX4 and -675 T → A in CYBA. No association was found between the genotype frequencies of NOX4 and CYBA SNPs and inflammation scores or fibrosis stages in the overall population. The presence of the CA + AA genotypes of the NOX4 SNP was nominally associated with a lower alanine aminotransferase (ALT) concentration in the male population (CA + AA = 72.23 ± 6.34 U/L versus CC = 100.22 ± 9.85; mean ± SEM; P = 0.05). The TT genotype of the CYBA SNP was also nominally associated with a lower ALT concentration in the male population (TT = 84.01 ± 6.77 U/L versus TA + AA = 109.67 ± 18.37 U/L; mean ± SEM; P = 0.047). The minor A-allele of the NOX4 SNP was inversely associated with the frequency of metabolic syndrome (MS) in the male population (odds ratio (OR): 0.15; 95% confidence interval (CI): 0.03 to 0.79; P = 0.025). The results suggest that the evaluated NOX4 and CYBA SNPs are not direct genetic determinants of fibrosis in HCV patients, but nevertheless NOX4 rs3017887 SNP could indirectly influence fibrosis susceptibility due to its inverse association with MS in male patients.

Hyaluronan Synthase 3 Variant and Anthracycline-Related Cardiomyopathy: A Report From the Children's Oncology Group

PubMed Central

Wang, Xuexia; Liu, Wei; Sun, Can-Lan; Armenian, Saro H.; Hakonarson, Hakon; Hageman, Lindsey; Ding, Yan; Landier, Wendy; Blanco, Javier G.; Chen, Lu; Quiñones, Adolfo; Ferguson, Daniel; Winick, Naomi; Ginsberg, Jill P.; Keller, Frank; Neglia, Joseph P.; Desai, Sunil; Sklar, Charles A.; Castellino, Sharon M.; Cherrick, Irene; Dreyer, ZoAnn E.; Hudson, Melissa M.; Robison, Leslie L.; Yasui, Yutaka; Relling, Mary V.; Bhatia, Smita

2014-01-01

Purpose The strong dose-dependent association between anthracyclines and cardiomyopathy is further exacerbated by the co-occurrence of cardiovascular risk factors (diabetes and hypertension). The high morbidity associated with cardiomyopathy necessitates an understanding of the underlying pathogenesis so that targeted interventions can be developed. Patients and Methods By using a two-stage design, we investigated host susceptibility to anthracycline-related cardiomyopathy by using the ITMAT/Broad CARe cardiovascular single nucleotide polymorphism (SNP) array to profile common SNPs in 2,100 genes considered relevant to de novo cardiovascular disease. Results By using a matched case-control design (93 cases, 194 controls), we identified a common SNP, rs2232228, in the hyaluronan synthase 3 (HAS3) gene that exerts a modifying effect on anthracycline dose-dependent cardiomyopathy risk (P = 5.3 × 10−7). Among individuals with rs2232228 GG genotype, cardiomyopathy was infrequent and not dose related. However, in individuals exposed to high-dose (> 250 mg/m2) anthracyclines, the rs2232228 AA genotype conferred an 8.9-fold (95% CI, 2.1- to 37.5-fold; P = .003) increased cardiomyopathy risk compared with the GG genotype. This gene-environment interaction was successfully replicated in an independent set of 76 patients with anthracycline-related cardiomyopathy. Relative HAS3 mRNA levels measured in healthy hearts tended to be lower among individuals with AA compared with GA genotypes (P = .09). Conclusion Hyaluronan (HA) produced by HAS3 is a ubiquitous component of the extracellular matrix and plays an active role in tissue remodeling. In addition, HA is known to reduce reactive oxygen species (ROS) –induced cardiac injury. The high cardiomyopathy risk associated with AA genotype could be due to inadequate remodeling and/or inadequate protection of the heart from ROS-mediated injury on high anthracycline exposure. PMID:24470002

Highly sensitive avidin-biotin ELISA for detection of nandrolone and testosterone in dietary supplements.

PubMed

Jurášek, Michal; Göselová, Sandra; Mikšátková, Petra; Holubová, Barbora; Vyšatová, Eva; Kuchař, Martin; Fukal, Ladislav; Lapčík, Oldřich; Drašar, Pavel

2017-04-01

Avidin-biotin technology was used for the implementation of an enzyme-linked immunosorbent assay (AB-ELISA) as a sensitive method for the detection of anabolic androgenic steroids (AAS) present in dietary supplements. Using click chemistry, novel haptens (linker-optimized biotinylated nandrolone (NT) and testosterone (T) at positions C-3 and C-17, respectively) were designed and synthesized to be then applied as four different immobilized competitors in a proposed set of four indirect competitive AB-ELISAs. Four rabbit polyclonal antibodies of various specificities were prepared using four different immunogens synthesized from C-3 and C-17 carboxymethyloxime and hemisuccinate derivatives of NT and T, respectively. Assembled AB-ELISAs were characterized to establish method parameters such as a half-maximum inhibition concentration (0.18-12.99 ng/mL), limit of detection (0.004-0.032 ng/mL) and linear working range (the best with 0.02-1.38 ng/mL). The stability of the set simulating storage in different conditions was demonstrated. Cross reactivity (CR) was tested for 59 steroids including both endogenous and synthetic analogues in four assembled AB-systems. The focus was placed on the practical use of the method in detection of various AAS in 49 samples of counterfeit dietary supplements. The concordance between ultra high performance liquid chromatography-mass spectrometry (UHPLC-MS) and the CR corrected data from AB-ELISA indicated the potential of this method even to quantification of T propionate, NT phenyl propionate, and NT decanoate in such a complex matter. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Single Nucleotide Polymorphism in ATM Gene, Cooking Oil Fumes and Lung Adenocarcinoma Susceptibility in Chinese Female Non-Smokers: A Case-Control Study

PubMed Central

Shen, Li; Yin, Zhihua; Wu, Wei; Ren, Yangwu; Li, Xuelian; Zhou, Baosen

2014-01-01

Background The ataxia-telangiectasia mutated (ATM) gene plays an important role in the DNA double-strand breaks repair pathway. Single nucleotide polymorphisms (SNPs) of DNA repair genes are suspected to influence the risk of lung cancer. This study aimed to investigate the association between the ATM -111G>A (rs189037) polymorphism, environmental risk factors and the risk of lung adenocarcinoma in Chinese female non-smokers. Methods A hospital-based case-control study of 487 lung cancer patients and 516 matched cancer-free controls was conducted. Information concerning demographic and environmental risk factors was obtained for each case and control by a trained interviewer. After informed consent was obtained, 10 ml venous blood was collected from each subject for biomarker testing. Single nucleotide polymorphism was determined by using TaqMan method. Results This study showed that the individuals with ATM rs189037 AA genotype were at an increased risk for lung adenocarcinoma compared with those carrying the GA or GG genotype (adjusted odds ratios (OR) 1.44, 95% confidence interval (CI) 1.02–2.02, P = 0.039). The stratified analysis suggested that increased risk associated with ATM rs189037 AA genotype in individuals who never or seldom were exposed to cooking oil fumes (adjusted OR 1.89, 95%CI 1.03–3.49, P = 0.040). Conclusions ATM rs189037 might be associated with the risk of lung adenocarcinoma in Chinese non-smoking females. Furthermore, ATM rs189037 AA genotype might be a risk factor of lung adenocarcinoma among female non-smokers without cooking oil fume exposure. PMID:24819391

Association of XPD/ERCC2 G23591A and A35931C polymorphisms with skin lesion prevalence in a multiethnic, arseniasis-hyperendemic village exposed to indoor combustion of high arsenic coal.

PubMed

Lin, Guo-fang; Du, Hui; Chen, Ji-gang; Lu, Hong-chao; Guo, Wei-chao; Golka, Klaus; Shen, Jian-hua

2010-01-01

More than 2,000 arsenic-related skin lesions (as at 2002) in a few villages of China's Southwest Guizhou Autonomous Prefecture represent a unique case of endemic arseniasis related with indoor combustion of high-arsenic coal. The skin lesion prevalence was significantly higher in ethnic Han villagers than in ethnic Hmong villagers. This study was focused on a possible involvement of XPD/ERCC2 G23591A and A35931C polymorphisms in risk modulation of skin lesions and in the body burden of As in this unique case of As exposure. G23591A and A35931C were genotyped by a PCR-based procedure. Total As contents in hair and urine samples as well as environmental samples of the homes of the two ethnic clans were analysed. A significant higher presentation of A/A35931 (homozygous wild) genotype in both clans was found in skin lesion patients, compared with their asymptomatic fellow villagers (67.1 vs. 46.3%, OR 2.36, 95% CI 1.35-4.14, P=0.002). Interestingly, the population frequencies of the A/A35931 genotype did not show significant differences between ethnic Han villagers and their Hmong neighbours (47.1 vs. 45.5%). Very low frequencies of homozygous and heterozygous variant genotypes of G23591A were recorded in the residents in target village. G/A23591 and A/A23591 were detected only in 3.2% (8/244) and 0.8% (2/244) of the villagers, respectively. The polymorphic status at the locus of A35931C might modulate the risk for arsenic-related skin lesions in the investigated groups.

Association between the cytotoxic T-lymphocyte antigen-4 mutations and the susceptibility to systemic lupus erythematosus; Contribution markers of inflammation and oxidative stress.

PubMed

Tanhapour, M; Vaisi-Raygani, A; Bahrehmand, F; Khazaei, M; Kiani, A; Rahimi, Z; Nomani, H; Tavilani, H; Pourmotabbed, T

2016-10-31

The cytotoxic T lymphocyte antigen-4 (CTLA-4) also known as CD152 (cluster of differentiation 152) is a crucial negative regulator of the immune system. This protein receptor provides negative signals in order to suppress T-cell activation and immune attack against self-antigens, although its role is unclear.  The ability of CTLA-4 to limit T cell-mediated immune response has made it a major target in treatment of tumors and autoimmune diseases such as systemic lupus erythematosus (SLE). In this study, we investigated whether CTLA-4 G-1661A and CTLA-4 T-1722C mutations are associated with SLE. So one hundred nine SLE patients and 101 gender and age-matched unrelated healthy controls were recruited for this case-control study. The promoter mutations were detected by PCR-RFLP, neopterin, malondialdehyde (MDA) and serum lipid concentration were determined by HPLC and enzyme assay, respectively. We found that both codominant (AA vs. GG) and recessive (AA vs. GA+GG) CTLA-4 G-1661A mutation significantly decreased the risk of SLE by 1.7 and 3.7 times, respectively.  Interestingly, SLE patients with AA genotypes of CTLA-4 G-1661A have lower neopterin and MDA concentration compared with GA+GG genotypes. The overall distribution of CTLA-4 T-1722C genotypes and alleles in SLE patients were similar to those in control group. In conclusion, our findings showed, that there is an association between systemic inflammatory markers, oxidative stress and the CTLA-4 G-1661A GG+AG genotypes, MDA and neopterin which are the most conventional risk factors for coronary heart disease, therefore these mutations may be consider as a risk factor for susceptibility to heart disease in SLE patients.

The In Vitro Influence of a Genetic Superoxide-Hydrogen Peroxide Imbalance on Immunosenescence.

PubMed

Barbisan, Fernanda; Azzolin, Verônica Farina; Ribeiro, Euler Esteves; Duarte, Marta Maria Medeiros Frescura; da Cruz, Ivana Beatrice Mânica

2017-08-01

As superoxide is a key molecule of inflammatory activation, superoxide-hydrogen peroxide (S-HP) imbalance genetically caused could alter immunosenescence patterns. To test this hypothesis, we collected and cultured peripheral blood mononuclear cells (PBMCs) carrier's different genotypes of a genetic polymorphism located in the superoxide dismutase manganese-dependent gene (Val16Ala-SOD2). We used an in vitro genetic model based on previous studies, which suggested an association between homozygous genotypes (AA and VV) and alterations in oxidative-inflammatory mediators. PBMCs collected from young healthy volunteers were cultured in the presence of phytohemagglutinin, as well as the following cell culture passages obtained from the 72-hour initial culture. Each follow passage started with the same cell concentration (1 × 10 5 cells). The general immunosenescence pattern was observed independent of SOD2 genotypes: cellular proliferation until the 15th passage, when cellular arrestment occurred in the G0/G1 phase. From the 10th passage, a higher proliferative state was observed, indicating inflammatory hyperactivation, with an increase in the levels of inflammatory cytokines (IL-1, IL-6, and TNFα), nitric oxide, superoxide, lipoperoxidation, protein carbonylation, reactive oxygen species, and DNA damage. The S-HP imbalance affected the intensity of some immunosenescence parameters. AA cells, which present basal high HP levels, were associated with higher DNA damage and lipoperoxidation levels, whereas VV, which present basal high S levels, was associated with higher proinflammatory cytokine levels. In summary, the results suggested that a basal S-HP imbalance could affect the intensity of some immunosenescence markers, and this influence could explain the potential association between an imbalance of genotypes (AA and VV) and the risk of developing some chronic diseases.

Analysis of rs8067378 Polymorphism in the Risk of Uterine Cervical Cancer from a Polish Population and its Impact on Gasdermin B Expression.

PubMed

Lutkowska, Anna; Roszak, Andrzej; Lianeri, Margarita; Sowińska, Anna; Sotiri, Emianka; Jagodziński, Pawel P

2017-04-01

We studied the role of the NC_000017.10:g.38051348A>G (rs8067378) single nucleotide polymorphism (SNP) located 9.5 kb downstream of gasdermin B (GSDMB), in the development and progression of cervical squamous cell carcinomas (SCC). Using high-resolution melting curve analysis, we genotyped this SNP in patients with cervical SCC (n = 486) and controls (n = 511) from the Polish Caucasian population. Logistic regression analysis was used to adjust for the effect of confounders such as age, parity, oral contraceptive use, tobacco smoking, and menopausal status. The effect of this SNP on the expression of GSDMB was studied by reverse transcription and quantitative real-time polymerase chain reaction analysis of GSDMB transcript levels in SCC tissues. For all patients with SCC, the p trend value calculated for rs8067378 was statistically significant (p trend  = 0.0019). The adjusted odds ratio for the G/G vs. A/A genotype was 1.304 (95% confidence interval 1.080-1.574, p = 0.0057) and the adjusted odds ratio for the G/A + G/G vs. A/A genotype was 1.444 (95% confidence interval 1.064-1.959, p = 0.0181). We also found a significant association of the rs8067378 SNP with tumor stages III, IV, and grade of differentiation G3, and with parity, oral contraceptive use, smoking, and women of postmenopausal age. We found increased GSDMB1 isoform transcripts in the cancerous and non-cancerous tissues from carriers of the G allele vs. carriers of the A/A genotype. The rs8067378 SNP variants may increase the expression of GSDMB and the risk of the development and progression of cervical SCC.

Wilhelm Weinberg’s Early Contribution to Segregation Analysis

PubMed Central

Stark, Alan; Seneta, Eugene

2013-01-01

Wilhelm Weinberg (1862–1937) is a largely forgotten pioneer of human and medical genetics. His name is linked with that of the English mathematician G. H. Hardy in the Hardy–Weinberg law, pervasive in textbooks on population genetics since it expresses stability over generations of zygote frequencies AA, Aa, aa under random mating. One of Weinberg’s signal contributions, in an article whose centenary we celebrate, was to verify that Mendel’s segregation law still held in the setting of human heredity, contrary to the then-prevailing view of William Bateson (1861–1926), the leading Mendelian geneticist of the time. Specifically, Weinberg verified that the proportion of recessive offspring genotypes aa in human parental crossings Aa × Aa (that is, the segregation ratio for such a setting) was indeed p=14. We focus in a nontechnical way on his procedure, called the simple sib method, and on the heated controversy with Felix Bernstein (1878–1956) in the 1920s and 1930s over work stimulated by Weinberg’s article. PMID:24018765

Association between Toll-like receptor 9 gene polymorphisms and risk of bacterial meningitis in a Chinese population.

PubMed

Wang, X H; Shi, H P; Li, F J

2016-07-25

We determined whether two common single nucleotide polymorphisms (SNPs) in the Toll-like receptor 9 gene (TLR9) (TLR9+2848 rs352140 and TLR9-1237 rs5743836) influenced susceptibility to bacterial meningitis in a Chinese population. The study comprised 126 patients with bacterial meningitis and 252 control subjects, all of whom were recruited from the Tuberculosis Hospital of Shanxi Province. Genotyping of TLR9+2848 rs352140 and TLR9-1237 rs5743836 was performed by polymerase chain reaction coupled with restriction fragment length polymorphism. Using logistic regression analysis, we found that individuals with the AA genotype were associated with an increased risk of bacterial meningitis compared with those with the GG genotype (OR = 0.43, 95%CI = 0.19-0.95; P = 0.03). In a recessive model, the AA genotype was correlated with an elevated risk of bacterial meningitis compared with the GG+GA genotype (OR = 0.49, 95%CI = 0.22-0.99; P = 0.04). However, no significant differences were observed in the association between the TLR9-1237 rs5743836 polymorphism and the risk of bacterial meningitis in the codominant, dominant, or recessive models. In conclusion, the results of our study suggest an association between the TLR9+2848 polymorphism and a reduced risk of bacterial meningitis in the codominant and recessive models.

Statistical Genomic Approach Identifies Association between FSHR Polymorphisms and Polycystic Ovary Morphology in Women with Polycystic Ovary Syndrome

PubMed Central

Du, Tao; Duan, Yu; Li, Kaiwen; Zhao, Xiaomiao; Ni, Renmin; Li, Yu; Yang, Dongzi

2015-01-01

Background. Single-nucleotide polymorphisms (SNPs) in the follicle stimulating hormone receptor (FSHR) gene are associated with PCOS. However, their relationship to the polycystic ovary (PCO) morphology remains unknown. This study aimed to investigate whether PCOS related SNPs in the FSHR gene are associated with PCO in women with PCOS. Methods. Patients were grouped into PCO (n = 384) and non-PCO (n = 63) groups. Genomic genotypes were profiled using Affymetrix human genome SNP chip 6. Two polymorphisms (rs2268361 and rs2349415) of FSHR were analyzed using a statistical approach. Results. Significant differences were found in the allele distributions of the GG genotype of rs2268361 between the PCO and non-PCO groups (27.6% GG, 53.4% GA, and 19.0% AA versus 33.3% GG, 36.5% GA, and 30.2% AA), while no significant differences were found in the allele distributions of the GG genotype of rs2349415. When rs2268361 was considered, there were statistically significant differences of serum follicle stimulating hormone, estradiol, and sex hormone binding globulin between genotypes in the PCO group. In case of the rs2349415 SNP, only serum sex hormone binding globulin was statistically different between genotypes in the PCO group. Conclusions. Functional variants in FSHR gene may contribute to PCO susceptibility in women with PCOS. PMID:26273622

Interactions between the APOA5 -1131T>C and the FEN1 10154G>T polymorphisms on ω6 polyunsaturated fatty acids in serum phospholipids and coronary artery disease

PubMed Central

Park, Ju Yeon; Paik, Jean Kyung; Kim, Oh Yoen; Chae, Jey Sook; Jang, Yangsoo; Lee, Jong Ho

2010-01-01

We determined the contribution of the combination of FEN1 10154G>T with the most significant association in the analysis of plasma arachidonic acid (AA, 20:4ω6) and the APOA5-1131T>C on phospholipid ω6PUFA and coronary artery disease (CAD). Patients with CAD (n = 807, 27–81 years of age) and healthy controls (n = 1123) were genotyped for FEN1 10154G>T and APOA5-1131T>C. We found a significant interaction between these two genes for CAD risk (P = 0.007) adjusted for confounding factors. APOA5-1131C allele carriers had a higher CAD risk [odds ratio (OR):1.484, 95% confidence interval (CI):1.31–1.96; P = 0.005] compared with APOA5-1131TT individuals in the FEN1 10154GG genotype group but not in the FEN1 10154T allele group (OR:1.096, 95%CI:0.84–1.43; P = 0.504). Significant interactions between these two genes were also observed for the AA proportion (P = 0.04) and the ratio of AA/linoleic acid (LA, 18:2ω6) (P = 0.004) in serum phospholipids of controls. The APOA5-1131C allele was associated with lower AA (P = 0.027) and AA/LA (P = 0.014) only in controls carrying the FEN1 10154T allele. In conclusion, the interaction between these genes suggests that the FEN1 10154T variant allele decreases AA and AA/LA in the serum phospholipids of carriers of the APOA5-1131C allele, but contributes no significant increase in CAD risk for this population subset despite their increased triglylcerides and decreased apoA5. PMID:20802161

Stacking orders induced direct band gap in bilayer MoSe2-WSe2 lateral heterostructures.

PubMed

Hu, Xiaohui; Kou, Liangzhi; Sun, Litao

2016-08-16

The direct band gap of monolayer semiconducting transition-metal dichalcogenides (STMDs) enables a host of new optical and electrical properties. However, bilayer STMDs are indirect band gap semiconductors, which limits its applicability for high-efficiency optoelectronic devices. Here, we report that the direct band gap can be achieved in bilayer MoSe2-WSe2 lateral heterostructures by alternating stacking orders. Specifically, when Se atoms from opposite layers are stacked directly on top of each other, AA and A'B stacked heterostructures show weaker interlayer coupling, larger interlayer distance and direct band gap. Whereas, when Se atoms from opposite layers are staggered, AA', AB and AB' stacked heterostructures exhibit stronger interlayer coupling, shorter interlayer distance and indirect band gap. Thus, the direct/indirect band gap can be controllable in bilayer MoSe2-WSe2 lateral heterostructures. In addition, the calculated sliding barriers indicate that the stacking orders of bilayer MoSe2-WSe2 lateral heterostructures can be easily formed by sliding one layer with respect to the other. The novel direct band gap in bilayer MoSe2-WSe2 lateral heterostructures provides possible application for high-efficiency optoelectronic devices. The results also show that the stacking order is an effective strategy to induce and tune the band gap of layered STMDs.

Small scale affinity purification and high sensitivity reversed phase nanoLC-MS N-glycan characterization of mAbs and fusion proteins.

PubMed

Higel, Fabian; Seidl, Andreas; Demelbauer, Uwe; Sörgel, Fritz; Frieß, Wolfgang

2014-01-01

N-glycosylation is a complex post-translational modification with potential effects on the efficacy and safety of therapeutic proteins and known influence on the effector function of biopharmaceutical monoclonal antibodies (mAbs). Comprehensive characterization of N-glycosylation is therefore important in biopharmaceutical development. In early development, e.g. during pool or clone selection, however, only minute protein amounts of multiple samples are available for analytics. High sensitivity and high throughput methods are thus needed. An approach based on 96-well plate sample preparation and nanoLC-MS of 2- anthranilic acid or 2-aminobenzoic acid (AA) labeled N-glycans for the characterization of biopharmaceuticals in early development is reported here. With this approach, 192 samples can be processed simultaneously from complex matrices (e.g., cell culture supernatant) to purified 2-AA glycans, which are then analyzed by reversed phase nanoLC-MS. Attomolar sensitivity has been achieved by use of nanoelectrospray ionization, resulting in detailed glycan maps of mAbs and fusion proteins that are exemplarily shown in this work. Reproducibility, robustness and linearity of the approach are demonstrated, making use in a routine manner during pool or clone selection possible. Other potential fields of application, such as glycan biomarker discovery from serum samples, are also presented.

Small scale affinity purification and high sensitivity reversed phase nanoLC-MS N-glycan characterization of mAbs and fusion proteins

PubMed Central

Higel, Fabian; Seidl, Andreas; Demelbauer, Uwe; Sörgel, Fritz; Frieß, Wolfgang

2014-01-01

N-glycosylation is a complex post-translational modification with potential effects on the efficacy and safety of therapeutic proteins and known influence on the effector function of biopharmaceutical monoclonal antibodies (mAbs). Comprehensive characterization of N-glycosylation is therefore important in biopharmaceutical development. In early development, e.g. during pool or clone selection, however, only minute protein amounts of multiple samples are available for analytics. High sensitivity and high throughput methods are thus needed. An approach based on 96-well plate sample preparation and nanoLC-MS of 2- anthranilic acid or 2-aminobenzoic acid (AA) labeled N-glycans for the characterization of biopharmaceuticals in early development is reported here. With this approach, 192 samples can be processed simultaneously from complex matrices (e.g., cell culture supernatant) to purified 2-AA glycans, which are then analyzed by reversed phase nanoLC-MS. Attomolar sensitivity has been achieved by use of nanoelectrospray ionization, resulting in detailed glycan maps of mAbs and fusion proteins that are exemplarily shown in this work. Reproducibility, robustness and linearity of the approach are demonstrated, making use in a routine manner during pool or clone selection possible. Other potential fields of application, such as glycan biomarker discovery from serum samples, are also presented. PMID:24848368

The M694I/M694I genotype: A genetic risk factor of AA-amyloidosis in a group of Algerian patients with familial Mediterranean fever.

PubMed

Ait-Idir, Djouher; Djerdjouri, Bahia; Bouldjennet, Faiza; Taha, Rowaida Z; El-Shanti, Hatem; Sari-Hamidou, Rawda; Khellaf, Ghalia; Benmansour, Mustapha; Benabadji, Mohamed; Haddoum, Farid

2017-03-01

Familial Mediterranean fever (FMF, OMIM 249100) is the most common hereditary fever, resulting from mutations in MEFV. FMF is characterized by episodic febrile attacks and polyserositis. Renal AA-amyloidosis is a major complication, which often leads to end-stage renal disease in untreated patients. The data about the renal AA-amyloidosis secondary to FMF are scarce in North African countries and non-existent in Algeria. We aimed to investigate the MEFV mutations associated with this complication in an Algerian patient cohort. Molecular analysis included 28 unrelated Algerian FMF patients with ascertained amyloidosis, 23 of them were symptomatic and 5 were asymptomatic. For this study, a group of 20 FMF patients without renal amyloidosis were selected as controls according to their age, disease onset and disease duration. The mutations were detected by sequencing exon 10 of MEFV. A total of 87.5% (49/56) mutant alleles were identified in 27/28 analyzed patients; p.M694I was predominant and appeared with an allele frequency of 62.5%, followed by p.M694V (17.85%), p.M680I (5.35%) and p.I692Del (1.78%). Remarkably, only p.M694I mutation was observed among the asymptomatic patients. The M694I/M694I genotype, identified in 14/27 (52%) patients, was significantly associated with the development of amyloidosis compared to group of controls (p = 0.022). This study did not link the M694V/M694V genotype to the renal complication despite the fact that it has been observed only in the patients with amyloidosis (3/27; 11%) (p = 0.349). The association of other identified genotypes to this complication was statistically insignificant. The progression of amyloidosis led to end-stage renal disease in 14 patients with 6 deaths. This study shows that p.M694I homozygosity is a potential genetic risk factor for the development of renal AA-amyloidosis in Algerian FMF patients. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Amino acid residues in the GerAB protein important in the function and assembly of the alanine spore germination receptor of Bacillus subtilis 168.

PubMed

Cooper, Gareth R; Moir, Anne

2011-05-01

The paradigm gerA operon is required for endospore germination in response to c-alanine as the sole germinant, and the three protein products, GerAA, GerAB, and GerAC are predicted to form a receptor complex in the spore inner membrane. GerAB shows homology to the amino acid-polyamine-organocation (APC) family of single-component transporters and is predicted to be an integral membrane protein with 10 membrane-spanning helices. Site-directed mutations were introduced into the gerAB gene at its natural location on the chromosome. Alterations to some charged or potential helix-breaking residues within membrane spans affected receptor function dramatically. In some cases, this is likely to reflect the complete loss of the GerA receptor complex, as judged by the absence of the germinant receptor protein GerAC, which suggests that the altered GerAB protein itself may be unstable or that the altered structure destabilizes the complex. Mutants that have a null phenotype for Instituto de Biotecnología de León, INBIOTEC, Parque Científico de León, Av. Real, 1, 24006 León, Spain-alanine germination but retain GerAC protein at near-normal levels are more likely to define amino acid residues of functional, rather than structural, importance. Single-amino-acid substitutions in each of the GerAB and GerAA proteins can prevent incorporation of GerAC protein into the spore; this provides strong evidence that the proteins within a specific receptor interact and that these interactions are required for receptor assembly. The lipoprotein nature of the GerAC receptor subunit is also important; an amino acid change in the prelipoprotein signal sequence in the gerAC1 mutant results in the absence of GerAC protein from the spore.

[Influence of occupational stress and 5-hydroxytryptamine 2A receptor gene polymorphisms on depression in workers in a thermal power plant].

PubMed

Wu, H; Wang, F F; Zhou, W H; Gu, G Z; Yu, S F

2016-10-20

Objective: To investigate the association of occupational stress and 5-hydroxytryptamine 2A (5-HT2A) receptor gene polymorphisms with depression. Methods: In November 2010, cluster sampling was used to select 589 workers in a thermal power plant as study subjects. Questionnaires were used to investigate demographic features and occupational stressors. Polymerase chain reaction-restriction fragment length polymorphism was used to detect the genotypes of T102C and A-1438G in 5-HT2A receptor gene in 589 workers. Results: High-level daily hassles ( OR =3.013, 95% CI 1.642~5.530) , more negative emotion ( OR =4.808, 95% CI 2.662~8.681) , more body needs ( OR =1.890, 95% CI 1.034~3.453) , and severe role conflict ( OR =1.815, 95% CI 1.002~3.288) were risk factors for depression, while high rewards ( OR =0.424, 95% CI 0.226~0.796) was the protective factor against depression (all P <0.05). There were no significant differences in T102C genotype and allele distributions between the groups with and without depression ( P >0.05) ; there was a significant difference in A-1438G genotype distribution between the groups with and without depression (χ 2 = 9.573, P <0.05) , while there was no significant difference in A-1438G allele distribution between these groups ( P >0.05). The risk of depression in the workers with high-level daily hassles who carried TC genotype ( OR = 4.473, 95% CI 1.161~17.238) or CC genotype ( OR =5.176, 95% CI 1.367~19.593) of T102C was 4.473 and 5.176 times that in those with low-level daily hassles who carried TT genotype, and the risk of depression in the workers with more negative emotions who carried TC genotype ( OR =5.667, 95% CI 1.204~26.673) or CC genotype ( OR =8.114, 95% CI 1.747~37.677) of T102C was 5.667 and 8.114 times that in those with less negative emotion who carried TT genotype. The risk of depression in the workers with high-level daily hassles who carried AG genotype ( OR =4.505, 95% CI 2.215~9.162) or GG genotype ( OR =6.484, 95% CI 2.562~ 16.414) of A-1438G was 4.505 and 6.484 times that in those with low-level daily hassles who carried AA genotype, and the risk of depression in the workers with more negative emotion who carried AG genotype ( OR = 4.877, 95% CI 2.326~10.223) or GG genotype ( OR =9.090, 95% CI 3.491~23.673) of A-1438G was 4.877 and 9.090 times that in those with less negative emotion who carried AA genotype. The risk of depression in the workers with higher rewards who carried AG genotype ( OR =0.152, 95% CI 0.074~0.310) or GG genotype ( OR = 0.384, 95% CI 0.153~0.964) of A-1438G was 0.152 and 0.384 times that in those with lower rewards who carried AA genotype. Conclusion: Occupational stress is associated with the development of depression and interacts with 5-HT2A receptor gene polymorphisms.

Bibliography of Soviet Laser Developments. Number 45, January - February 1980.

DTIC Science & Technology

1980-10-28

Smirnov, A.N. Sukhanov , and A.B. Yastrebkov (1). High-power NH. laser tunable In the 770-890 cm range. Fizicheskiy Institut AN SSSR. Preprint...no. 115, 1979, 55 p. (RZhF, 1/80, 1D1046) 71. Vasil’yev, B.I., A.Z. Grasyuk, A.P. Dyad’kin, A.N. Sukhanov , and A.B. Yastrebkov (1). High-power...1980, 741-760. 613. Bakeyev, A.A., B.A. Barikhin, V.V. Borovkov, L.A. Vasil’yev, L.I. Nikolashina, A.I. Pavlovskiy, N.V. Prokopenko, L.V. Sukhanov , A.I

The plasminogen activator inhibitor-1 (PAI-1) gene -844 A/G and -675 4G/5G promoter polymorphism significantly influences plasma PAI-1 levels in women with polycystic ovary syndrome.

PubMed

Lin, Sun; Huiya, Zhang; Bo, Liu; Wei, Wei; Yongmei, Guan

2009-12-01

Mutations in the plasminogen activator inhibitor-1 (PAI-1) gene, along with increased PAI-1 levels, have been implicated in the pathogenesis of polycystic ovarian syndrome (PCOS). We investigated a possible influence of the promoter polymorphism (-844 A/G and -675 4G/5G) in the PAI-1 gene on plasma PAI-1 levels in 126 PCOS patients and 97 healthy controls. Levels of total testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), fasting plasma glucose (FPG), fasting insulin, and PAI-1 were measured, and body mass index (BMI), waist-to-hip ratio (WHR), LH/FSH ratio, and homeostasis model assessment for insulin resistance (HOMA-IR) were calculated. PAI-1 -675 4G/5G and -844 A/G gene polymorphisms were also performed. Total testosterone, fasting insulin, and PAI-1 levels; BMI, LH/FSH, and HOMA-IR were significantly higher in PCOS patients than controls (P < 0.05). The odds ratio of 4G/4G genotype, 4G allele, and the combination genotype of 4G/4G and -844 A/A were 2.49 (95% confidence interval (CI), 1.4-4.44), 2.1 (95% CI, 1.43-3.08), and 2.9 (95% CI, 1.41-5.98), respectively, (P < 0.001). In the PCOS group, the PAI-1 level of the A/A was significantly higher than that of the A/G or G/G genotype, similarly was 4G/4G genotype compared with 4G/5G or 5G/5G genotype. The plasma PAI-1 levels of the combination of the PAI-1 -844 A/A and -675 4G/4G or 4G/5G genotypes, or the coadunation of 4G/4G and -844 non-G/G (A/A + A/G) genotypes were significantly high in PCOS women compared with controls. A trend to a positive interaction between PAI-1 -675 4G/5G and -844 A/G gene polymorphism may elevate plasma PAI-1 levels and hypofibrinolysis, which is probably an important hereditary risk factor in PCOS.

A gene trap transposon eliminates haematopoietic expression of zebrafish Gfi1aa, but does not interfere with haematopoiesis.

PubMed

Thambyrajah, Roshana; Ucanok, Deniz; Jalali, Maryam; Hough, Yasmin; Wilkinson, Robert Neil; McMahon, Kathryn; Moore, Chris; Gering, Martin

2016-09-01

A transposon-mediated gene trap screen identified the zebrafish line qmc551 that expresses a GFP reporter in primitive erythrocytes and also in haemogenic endothelial cells, which give rise to haematopoietic stem and progenitor cells (HSPCs) that seed sites of larval and adult haematopoiesis. The transposon that mediates this GFP expression is located in intron 1 of the gfi1aa gene, one of three zebrafish paralogs that encode transcriptional repressors homologous to mammalian Gfi1 and Gfi1b proteins. In qmc551 transgenics, GFP expression is under the control of the endogenous gfi1aa promoter, recapitulates early gfi1aa expression and allows live observation of gfi1aa promoter activity. While the transposon integration interferes with the expression of gfi1aa mRNA in haematopoietic cells, homozygous qmc551 fish are viable and fertile, and display normal primitive and definitive haematopoiesis. Retained expression of Gfi1b in primitive erythrocytes and up-regulation of Gfi1ab at the onset of definitive haematopoiesis in homozygous qmc551 carriers, are sufficient to allow normal haematopoiesis. This finding contradicts previously published morpholino data that suggested an essential role for zebrafish Gfi1aa in primitive erythropoiesis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Genetic basis of Bartter syndrome in Korea.

PubMed

Lee, Beom Hee; Cho, Hee Yeon; Lee, HyunKyung; Han, Kyoung Hee; Kang, Hee Gyung; Ha, Il Soo; Lee, Joo Hoon; Park, Young Seo; Shin, Jae Il; Lee, Dae-Yeol; Kim, Su-Yung; Choi, Yong; Cheong, Hae Il

2012-04-01

Bartter syndrome (BS) is clinically classified into antenatal or neonatal BS (aBS) and classic BS (cBS) as well as five subtypes based on the underlying mutant gene; SLC12A1 (BS I), KCNJ1 (BS II), CLCNKB (BS III), BSND (BS IV) and CASR (BS V). Clinico-genetic features of a nationwide cohort of 26 Korean children with BS were investigated. The clinical diagnosis was aBS in 8 (30.8%), cBS in 15 (57.7%) and mixed Bartter-Gitelman phenotype in 3 cases (11.5%). Five of eight patients with aBS and all 18 patients with either cBS or mixed Bartter-Gitelman phenotype had CLCNKB mutations. Among the 23 patients (46 alleles) with CLCNKB mutations, p.W610X and large deletions were detected in 25 (54.3%) and 10 (21.7%) alleles, respectively. There was no genotype-phenotype correlation in patients with CLCNKB mutations. Twenty-three (88.5%) of the 26 BS patients involved in this study had CLCNKB mutations. The p.W610X mutation and large deletion were two common types of mutations in CLCNKB. The clinical manifestations of BS III were heterogeneous without a genotype-phenotype correlation, typically manifesting cBS phenotype but also aBS or mixed Bartter-Gitelman phenotypes. The molecular diagnostic steps for patients with BS in our population should be designed taking these peculiar genotype distributions into consideration, and a new more clinically relevant classification including BS and Gitelman syndrome is required.

Is diabetes mellitus-linked amino acid signature associated with β-blocker-induced impaired fasting glucose?

PubMed

Cooper-Dehoff, Rhonda M; Hou, Wei; Weng, Liming; Baillie, Rebecca A; Beitelshees, Amber L; Gong, Yan; Shahin, Mohamed H A; Turner, Stephen T; Chapman, Arlene; Gums, John G; Boyle, Stephen H; Zhu, Hongjie; Wikoff, William R; Boerwinkle, Eric; Fiehn, Oliver; Frye, Reginald F; Kaddurah-Daouk, Rima; Johnson, Julie A

2014-04-01

The 5-amino acid (AA) signature, including isoleucine, leucine, valine, tyrosine, and phenylalanine, has been associated with incident diabetes mellitus and insulin resistance. We investigated whether this same AA signature, single-nucleotide polymorphisms in genes in their catabolic pathway, was associated with development of impaired fasting glucose (IFG) after atenolol treatment. Among 234 European American participants enrolled in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study and treated with atenolol for 9 weeks, we prospectively followed a nested cohort that had both metabolomics profiling and genotype data available for the development of IFG. We assessed the association between baseline circulating levels of isoleucine, leucine, valine, tyrosine, and phenylalanine, as well as single-nucleotide polymorphisms in branched-chain amino-acid transaminase 1 (BCAT1) and phenylalanine hydroxylase (PAH) with development of IFG. All baseline AA levels were strongly associated with IFG development. Each increment in standard deviation of the 5 AAs was associated with the following odds ratio and 95% confidence interval for IFG based on a fully adjusted model: isoleucine 2.29 (1.31-4.01), leucine 1.80 (1.10-2.96), valine 1.77 (1.07-2.92), tyrosine 2.13 (1.20-3.78), and phenylalanine 2.04 (1.16-3.59). The composite P value was 2×10(-5). Those with PAH (rs2245360) AA genotype had the highest incidence of IFG (P for trend=0.0003). Our data provide important insight into the metabolic and genetic mechanisms underlying atenolol-associated adverse metabolic effects. Clinical Trial Registration- http://www.clinicaltrials.gov; Unique Identifier: NCT00246519.

Common Genetic Variation in CYP17A1 and Response to Abiraterone Acetate in Patients with Metastatic Castration-Resistant Prostate Cancer

PubMed Central

Binder, Moritz; Zhang, Ben Y.; Hillman, David W.; Kohli, Rhea; Kohli, Tanvi; Lee, Adam; Kohli, Manish

2016-01-01

Treatment with abiraterone acetate and prednisone (AA/P) prolongs survival in metastatic castration-resistant prostate cancer (mCRPC) patients. We evaluated the genetic variation in CYP17A1 as predictive of response to AA/P. A prospective collection of germline DNA prior to AA/P initiation and follow-up of a mCRPC cohort was performed. Five common single-nucleotide polymorphisms (SNPs) in CYP17A1 identified using a haplotype-based tagging algorithm were genotyped. Clinical outcomes included biochemical response and time to biochemical progression on AA/P. Logistic regression was used to assess the association between tag SNPs and biochemical response. Proportional hazards regression was used to assess the association between tag SNPs and time to biochemical progression. Odds or hazard ratio per minor allele were estimated and p-values below 0.05 were considered statistically significant. Germline DNA was successfully genotyped for four tag SNPs in 87 patients. The median age was 73 years (54–90); the median prostate-specific antigen was 66 ng/dL (0.1–99.9). A single SNP, rs2486758, was associated with lower odds of experiencing a biochemical response (Odds ratio 0.22, 95% confidence interval 0.07–0.63, p = 0.005) and a shorter time to biochemical progression (Hazard ratio 2.23, 95% confidence interval 1.39–3.56, p < 0.001). This tag SNP located in the promoter region of CYP17A1 will need further validation as a predictive biomarker for AA/P therapy. PMID:27409606

Association of FAS A-670G Polymorphism and Risk of Uterine Leiomyoma in a Southeast Iranian Population

PubMed Central

Mohammadpour-Gharehbagh, Abbas; Salimi, Saeedeh; Keshavarzi, Farshid; Zakerian, Sepideh; Sajadian, Mojtaba; Mokhtari, Mojgan

2016-01-01

Background: Uterine leiomyoma (UL) is a benign tumor of uterine smooth muscle that affects women in reproductive ages. FAS has an important role in initial stages of apoptosis. Previous studies have shown an association between the FAS gene and tumorigenesis. In the present study, we evaluated the relationship between FAS A-670G (rs 1800682) and UL risk Methods: The FAS gene polymorphism of 155 women with UL and 157 healthy controls was analyzed by the polymerase chain reaction restriction fragment length polymorphism method Results: The AA, AG, and GG genotype frequencies of the FAS A-670G polymorphism were respectively 37.4, 42.6, and 20% in women with UL, and 46, 42.6, and 11.5% in healthy controls. The risk of UL in women was 1.5-fold greater in GG-genotype women than in AA-genotype women. The G allele frequencies were 41% in women with UL and 33% in healthy controls and statistically different (P = 0.03) Conclusion: The FAS polymorphism was associated with the risk of UL in a sample of Iranian women. PMID:28070535

Comparison of fluorescent tags for analysis of mannose-6-phosphate glycans.

PubMed

Kang, Ji-Yeon; Kwon, Ohsuk; Gil, Jin Young; Oh, Doo-Byoung

2016-05-15

Mannose-6-phosphate (M-6-P) glycan analysis is important for quality control of therapeutic enzymes for lysosomal storage diseases. Here, we found that the analysis of glycans containing two M-6-Ps was highly affected by the hydrophilicity of the elution solvent used in high-performance liquid chromatography (HPLC). In addition, the performances of three fluorescent tags--2-aminobenzoic acid (2-AA), 2-aminobenzamide (2-AB), and 3-(acetyl-amino)-6-aminoacridine (AA-Ac)--were compared with each other for M-6-P glycan analysis using HPLC and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The best performance for analyzing M-6-P glycans was shown by 2-AA labeling in both analyses. Copyright © 2016 Elsevier Inc. All rights reserved.

76 FR 29147 - Federal Home Loan Bank Investments

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-20

...-AA32 Federal Home Loan Bank Investments AGENCY: Federal Housing Finance Agency; Federal Housing Finance...-adopting existing investment regulations that apply to the Federal Home Loan Banks (Banks) and that were...' investment in mortgage-backed securities (MBS) and certain asset-backed securities (ABS) that were previously...

PDGF-AA promotes osteogenic differentiation and migration of mesenchymal stem cell by down-regulating PDGFRα and derepressing BMP-Smad1/5/8 signaling.

PubMed

Li, Anna; Xia, Xuechun; Yeh, James; Kua, Huiyi; Liu, Huijuan; Mishina, Yuji; Hao, Aijun; Li, Baojie

2014-01-01

Platelet-derived growth factors (PDGFs) play important roles in skeletal development and bone fracture healing, yet how PDGFs execute their functions remains incompletely understood. Here we show that PDGF-AA, but not -AB or -BB, could activate the BMP-Smad1/5/8 pathway in mesenchymal stem cells (MSCs), which requires BMPRIA as well as PDGFRα. PDGF-AA promotes MSC osteogenic differentiation through the BMP-Smad1/5/8-Runx2/Osx axis and MSC migration via the BMP-Smad1/5/8-Twist1/Atf4 axis. Mechanistic studies show that PDGF-AA activates BMP-Smad1/5/8 signaling by feedback down-regulating PDGFRα, which frees BMPRI and allows for BMPRI-BMPRII complex formation to activate smad1/5/8, using BMP molecules in the microenvironment. This study unravels a physical and functional interaction between PDGFRα and BMPRI, which plays an important role in MSC differentiation and migration, and establishes a link between PDGF-AA and BMPs pathways, two essential regulators of embryonic development and tissue homeostasis.

Molecular evolution of the HoxA cluster in the three major gnathostome lineages

PubMed Central

Chiu, Chi-hua; Amemiya, Chris; Dewar, Ken; Kim, Chang-Bae; Ruddle, Frank H.; Wagner, Günter P.

2002-01-01

The duplication of Hox clusters and their maintenance in a lineage has a prominent but little understood role in chordate evolution. Here we examined how Hox cluster duplication may influence changes in cluster architecture and patterns of noncoding sequence evolution. We sequenced the entire duplicated HoxAa and HoxAb clusters of zebrafish (Danio rerio) and extended the 5′ (posterior) part of the HoxM (HoxA-like) cluster of horn shark (Heterodontus francisci) containing the hoxa11 and hoxa13 orthologs as well as intergenic and flanking noncoding sequences. The duplicated HoxA clusters in zebrafish each house considerably fewer genes and are dramatically shorter than the single HoxA clusters of human and horn shark. We compared the intergenic sequences of the HoxA clusters of human, horn shark, zebrafish (Aa, Ab), and striped bass and found extensive conservation of noncoding sequence motifs, i.e., phylogenetic footprints, between the human and horn shark, representing two of the three gnathostome lineages. These are putative cis-regulatory elements that may play a role in the regulation of the ancestral HoxA cluster. In contrast, homologous regions of the duplicated HoxAa and HoxAb clusters of zebrafish and the HoxA cluster of striped bass revealed a striking loss of conservation of these putative cis-regulatory sequences in the 3′ (anterior) segment of the cluster, where zebrafish only retains single representatives of group 1, 3, 4, and 5 (HoxAa) and group 2 (HoxAb) genes and in the 5′ part of the clusters, where zebrafish retains two copies of the group 13, 11, and 9 genes, i.e., AbdB-like genes. In analyzing patterns of cis-sequence evolution in the 5′ part of the clusters, we explicitly looked for evidence of complementary loss of conserved noncoding sequences, as predicted by the duplication-degeneration-complementation model in which genetic redundancy after gene duplication is resolved because of the fixation of complementary degenerative mutations. Our data did not yield evidence supporting this prediction. We conclude that changes in the pattern of cis-sequence conservation after Hox cluster duplication are more consistent with being the outcome of adaptive modification rather than passive mechanisms that erode redundancy created by the duplication event. These results support the view that genome duplications may provide a mechanism whereby master control genes undergo radical modifications conducive to major alterations in body plan. Such genomic revolutions may contribute significantly to the evolutionary process. PMID:11943847

Genomewide association study of cocaine dependence and related traits: FAM53B identified as a risk gene

PubMed Central

Gelernter, Joel; Sherva, Richard; Koesterer, Ryan; Almasy, Laura; Zhao, Hongyu; Kranzler, Henry R.; Farrer, Lindsay

2013-01-01

We report a GWAS for cocaine dependence (CD) in three sets of African- and European-American subjects (AAs and EAs, respectively), to identify pathways, genes, and alleles important in CD risk. The discovery GWAS dataset (n=5,697 subjects) was genotyped using the Illumina OmniQuad microarray (890,000 analyzed SNPs). Additional genotypes were imputed based on the 1000 Genomes reference panel. Top-ranked findings were evaluated by incorporating information from publicly available GWAS data from 4,063 subjects. Then, the most significant GWAS SNPs were genotyped in 2,549 independent subjects. We observed one genomewide-significant (GWS) result: rs7086629 at the FAM53B (“family with sequence similarity 53, member B”) locus. This was supported in both AAs and EAs; p-value (meta-analysis of all samples) =4.28×10−8. The gene maps to the same chromosomal region as the maximum peak we observed in a previous linkage study. NCOR2 (nuclear receptor corepressor 1) SNP rs150954431 was associated with p=1.19×10−9 in the EA discovery sample. SNP rs2456778, which maps to CDK1 (“cyclin-dependent kinase 1”), was associated with cocaine-induced paranoia in AAs in the discovery sample only (p=4.68×10−8). This is the first study to identify risk variants for CD using GWAS. Our results implicate novel risk loci and provide insights into potential therapeutic and prevention strategies. PMID:23958962

A Functional ATG16L1 (T300A) Variant is Associated with Necrotizing Enterocolitis in Premature Infants

PubMed Central

Sampath, Venkatesh; Bhandari, Vineet; Berger, Jessica; Merchant, Daniel; Zhang, Liyun; Ladd, Mihoko; Menden, Heather; Garland, Jeffery; Ambalavanan, Namasivayam; Mulrooney, Neil; Quasney, Michael; Dagle, John; Lavoie, Pascal M; Simpson, Pippa; Dahmer, Mary

2017-01-01

Background The genetic basis of dysfunctional immune responses in necrotizing enterocolitis (NEC) remains unknown. We hypothesized that variants in Nucleotide binding and Oligomerization Domain (NOD)-Like Receptors (NLRs) and Autophagy (ATG) genes modulate vulnerability to NEC. Methods We genotyped a multi-center cohort of premature infants with and without NEC for NOD1, NOD2, ATG16L1, CARD8 and NLRP3 variants. Chi-square tests and logistic regression were used for statistical analysis. Results In our primary cohort (n=1015), 86 (8.5%) infants developed NEC. The A allele of the ATG16L1 (Thr300Ala) variant was associated with increased NEC (AA vs. AG vs. GG; 11.3% vs. 8.4% vs. 4.8%, p=0.009). In regression models for NEC that adjusted for epidemiological confounders, GA (p=0.033) and the AA genotype (p=0.038) of ATG16L1 variant were associated with NEC. The association between the A allele of the ATG16L1 variant and NEC remained significant among Caucasian infants (p=0.02). In a replication cohort (n=259), NEC rates were highest among infants with the AA genotype but did not reach statistical significance. Conclusion We report a novel association between a hypomorphic variant in an autophagy gene (ATG16L1) and NEC in premature infants. Our data suggest that decreased autophagy arising from genetic variants may confer protection against NEC. PMID:27893720

Donor CTLA-4 genotype influences clinical outcome after T cell-depleted allogeneic hematopoietic stem cell transplantation from HLA-identical sibling donors.

PubMed

Bosch-Vizcaya, Anna; Pérez-García, Arianne; Brunet, Salut; Solano, Carlos; Buño, Ismael; Guillem, Vicent; Martínez-Laperche, Carolina; Sanz, Guillermo; Barrenetxea, Cristina; Martínez, Carmen; Tuset, Esperanza; Lloveras, Natàlia; Coll, Rosa; Guardia, Ramon; González, Yolanda; Roncero, Josep M; Bustins, Anna; Gardella, Santiago; Fernández, Cristalina; Buch, Joan; Gallardo, David

2012-01-01

CTLA-4 (cytotoxic T-lymphocyte antigen-4) plays a pivotal role in inhibiting T cell activation through competitive interaction with B7 molecules and interruption of costimulatory signals mediated by CD28. Polymorphisms on the CTLA-4 gene have been previously associated with autoimmune diseases, predisposition to leukemic relapse, and with graft-versus-host disease (GVHD) or relapse after allogeneic transplant. As CTLA-4 is expressed on T-lymphocytes, the aim of this study was to determine whether the donor CTLA-4 CT60 genotype also influences clinical outcome even after T cell depletion with CD34-positive selection. We studied 136 patient-donor pairs. Overall survival (OS) was worse for those patients who received grafts from a donor with the CT60 AA genotype rather than from a donor with the AG or GG genotype (35.6% vs 49.4%; P = .043). This association was confirmed through multivariate analysis, which identified the donor CT60 genotype as an independent risk factor for OS (P = .008; hazard ratio [HR]: 2.24, 95% confidence interval [CI]: 1.23-4.08). The donor CT60 AA genotype was also associated with lower disease-free survival, this being related to an increased risk of relapse (P = .001; HR: 3.41, 95% CI: 1.67-6.96) and a trend toward higher transplant-related mortality. These associations were stronger when considering only patients in the early stage of disease. Our results suggest that graft-versus-leukemia (GVL) activity after T cell depletion is conditioned by the donor CTLA-4 genotype. Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Genetic and environmental risks for high blood pressure among African American mothers and daughters.

PubMed

Taylor, Jacquelyn Y; Maddox, Rosanna; Wu, Chun Yi

2009-07-01

To determine the relationship between genetic and environmental lifestyle factors (physical activity and sodium) on blood pressure (BP) among African-American women. In this cross-sectional study involving 108 African-American mothers and daughters from a Midwestern area, investigators obtained BP measurements, information on minutes of physical activity, amount of sodium intake, and buccal swab saliva samples. Of the 4 single nucleotide polymorphisms (SNPs) on the sodium bicarbonate cotransporter gene (SLC4A5), rs8179526 had a statistically significant interaction with cytosine/thymine (C/T) genotype by sodium status on systolic BP (SBP; p=.0077). For gene x physical activity interaction, 2 significant interactions (cytosine/adenine [C/A] genotype by physical activity and adenine/adenine [A/A] genotype by physical activity, p=.0107 and p=.0171, respectively) on SBP and 1 on diastolic BP (DBP; A/A genotype by physical activity, p=.0233) were found on rs1017783. Two significant guanine/adenine [G/A] genotype by physical activity interactions were found on rs6731545 for SBP and DBP (p=.0160 and p=.0492, respectively). A gene x environmental interaction with rs8179526 has a protective effect on SBP in African-American women with high sodium intake. Participants with C/T genotype of rs8179526 who consumed greater than 2,300 mg of sodium had lower SBP than those who consumed less than recommended. Women with thymine/thymine (T/T) genotype of rs8179526 who consumed greater than 2,300 mg had lower SBP than those who consumed less. Awareness of both the protective and deleterious properties of rs8179526 in African-American women may one day assist in determining appropriate treatment plans.

Genetic Polymorphisms of IL17 and Chagas Disease in the South and Southeast of Brazil.

PubMed

Reis, Pâmela Guimarães; Ayo, Christiane Maria; de Mattos, Luiz Carlos; Brandão de Mattos, Cinara de Cássia; Sakita, Karina Mayumi; de Moraes, Amarilis Giaretta; Muller, Larissa Pires; Aquino, Julimary Suematsu; Conci Macedo, Luciana; Mazini, Priscila Saamara; Sell, Ana Maria; Marques, Divina Seila de Oliveira; Bestetti, Reinaldo Bulgarelli; Visentainer, Jeane Eliete Laguila

2017-01-01

The aim of this study was to investigate possible associations between genetic polymorphisms of IL17A G197A (rs2275913) and IL17F T7488C (rs763780) with Chagas Disease (CD) and/or the severity of left ventricular systolic dysfunction (LVSD) in patients with chronic Chagas cardiomyopathy (CCC). The study with 260 patients and 150 controls was conducted in the South and Southeast regions of Brazil. The genotyping was performed by PCR-RFLP. The A allele and A/A genotype of IL17A were significantly increased in patients and their subgroups (patients with CCC; patients with CCC and LVSD; and patients with CCC and severe LVSD) when compared to the control group. The analysis according to the gender showed that the A/A genotype of IL17A was more frequent in female with LVSD and mild to moderate LVSD and also in male patients with LVSD. The frequency of IL17F T/C genotype was higher in male patients with CCC and severe LVSD and in female with mild to moderate LVSD. The results suggest the possible involvement of the polymorphisms of IL17A and IL17F in the susceptibility to chronic Chagas disease and in development and progression of cardiomyopathy.

The European GWAS-identified risk SNP rs457717 within IQGAP2 is not associated with age-related hearing impairment in Han male Chinese population.

PubMed

Luo, Huajie; Wu, Hao; Shen, Hailian; Chen, Haifeng; Yang, Tao; Huang, Zhiwu; Jin, Xiaojie; Pang, Xiuhong; Li, Lei; Hu, Xianting; Jiang, Xuemei; Fan, Zhuping; Li, Jiping

2016-07-01

This study aimed to test the association between the European GWAS-identified risk IQGAP2 SNP rs457717 (A>G) and age-related hearing impairment (ARHI) in a Han male Chinese (HMC) population. A total of 2420 HMC subjects were divided into two groups [group 70+: >70 years (n = 1306), and group 70-: ≤70 years (n = 1114)]. The participants were categorised into case and control groups according to Z high scores for group 70- and the severity of hearing loss and different audiogram shapes identified by K-means cluster analysis for group 70+. The IQGAP2 tagSNP rs457717 was genotyped in accordance with the different ARHI phenotypes. The genotype distributions of IQGAP2 (AA/AG/GG) were not significantly different between the case and control groups (P = 0.613 for group 70-; P = 0.602 for group 70+). Compared with genotype AA, the ORs of genotypes AG and GG for ARHI were not significantly different following adjustment for other environmental risk factors. We demonstrated that the IQGAP2 TagSNP rs457717 (A/G) was not associated with ARHI in HMC individuals.

Polymer absorption in dense polymer brushes vs. polymer adsorption on the brush-solvent interface

NASA Astrophysics Data System (ADS)

Milchev, Andrey; Binder, Kurt

2014-06-01

Molecular-dynamics simulations of a coarse-grained model of a dense brush of flexible polymers (of type A) interacting with a long flexible macromolecule (of type B) are presented, considering the case of an attractive AB interaction, while effective interactions between AA and BB pairs of monomers are repulsive. Varying the strength \\varepsilon_{AB} of the attraction between unlike monomers, an adsorption transition at some critical value \\varepsilon^c_{AB} is found, where the B-chain is bound to the brush-solvent interface, similar to the adsorption on a planar solid substrate. However, when \\varepsilon_{AB} is much higher than \\varepsilon^c_{AB} , the long macromolecule is gradually “sucked in” the brush, developing many pieces that are locally stretched in the z-direction perpendicular to the substrate, in order to fit between the brush chains. The resulting hairpin-like structures of the absorbed chain shows up via oscillatory decay of the bond vector autocorrelation function. Chain relaxation is only possible via reptation.

Erythrocyte polyunsaturated fatty acid composition is associated with depression and FADS genotype in Caucasians.

PubMed

Cribb, Lachlan; Murphy, Jenifer; Froud, Amy; Oliver, Georgina; Bousman, Chad A; Ng, Chee H; Sarris, Jerome

2017-05-29

Polyunsaturated fatty acids (PUFAs) play an important role in the pathophysiology of major depressive disorder (MDD), related, in part, to their role in inflammatory systems. The enzymes δ-5 and δ-6 desaturase are the rate-limiting steps in the metabolism of PUFAs and are encoded in the genes fatty acid desaturase (FADS) 1 and 2, respectively. Single nucleotide polymorphisms (SNPs) and haplotypes within the FADS gene cluster have been shown to influence PUFA composition. The objective of this study was to determine whether key omega-3 (n-3) and omega-6 (n-6) fatty acids may be associated with depression, and to explore the role of FADS genotype in PUFA variation. Four erythrocyte long chain (LC) fatty acids (linoleic acid [LA], α-linolenic acid [ALA], arachidonic acid [AA] and Eicosapentaenoic acid [EPA]), as well as six SNPs (rs174537, rs174547, rs174570, rs174575, rs498793 and rs3834458) within the FADS gene cluster were measured in a sample of 207 participants (154 with MDD versus 53 non-depressed controls). The precursor LC-PUFAs LA and ALA appeared to be negatively associated with depression (P < 0.001 and P < 0.01, respectively), while AA:LA (surrogate measure of desaturase activity) was positively associated with depression (P < 0.01). No significant differences were noted in erythrocyte EPA, AA or AA:EPA between groups. Minor alleles of each SNP (excluding rs498793) were associated with variation in desaturase activity and LA. Both rs174537 and rs174547 were associated with ALA. No genotype was associated with EPA or AA. Minor alleles of rs174537 and rs174547 were significantly associated with lower odds of MDD (although significance was lost after correction for multiple comparisons). Precursor LC-PUFAs, LA and ALA, appear to be associated with MDD and potentially modulated by genetic variation in the FADS gene cluster. These results provide support for the consideration of PUFA composition, diet and FADS genetic variation in the pathophysiology of MDD.

[Role of IFN-γ + 874 genetic polymorphisms in allogeneic hematopoietic stem cell transplantation].

PubMed

Cai, Xiao-jin; Song, A-xia; Wang, Hua; Zhang, Ping; Zhang, Gui-xin; Yang, Fan; Wei, Jia-lin; Ma, Qiao-ling; Yan, Zhang-song; Jiang, Er-lie; Huang, Yong; Wang, Mei; He, Yi; Feng, Si-zhou; Han, Ming-zhe

2012-12-01

To explore the impact of IFN-γ + 874 polymorphisms on the outcome in HLA matched sibling HSCT. We used PCR-sequence-specific primer analysis (PCR-SSP) to analyze the polymorphisms of IFN-γ + 874 T/A in 80 recipient and donor pairs from October 2005 to March 2008. Recipients having donors who possessed IFN-γ + 874 A/A genotype had significantly earlier neutrophil recovery compared with those having donors with non-A/A genotype (15 (11 - 27) days vs 18 (12 - 30) days, P = 0.029). And IFN-γ + 874 A/A in both recipients and donors further facilitated neutrophil recovery compared with others (13 (11 - 25) days and 19 (12 - 31) days, P = 0.019). Besides, IFN-γ + 874 A/A in recipients increased the probability of grade II-IV acute graft versus disease (aGVHD) and cytomegalovirus viraemia compared with IFN-γ + 874 T/A or T/T genotype (20% vs 4% P = 0.041, 43.6% vs 16.0% P = 0.032), which lead to increased 5-year transplant-related mortality (TRM) (33.7% ± 6.8% vs 12.0% ± 6.5%, P = 0.050) and decreased 5-year event free survival (EFS) \\[(58.2 ± 6.7)% vs (84.0 ± 7.3)%, P = 0.032\\] compared with the latter. IFN-γ + 874 A/A in both recipients and donors also significantly increased the probability of grade II-IV aGVHD and cytomegalovirus viraemia compared with the other (21.7% vs 5.9%, P = 0.050; 45.7% vs 20.6%, P = 0.020), which caused increased 5-year TRM \\[(31.6 ± 7.5)% vs (13.6 ± 6.5)%, P = 0.048\\] and decreased 5-year EFS \\[(56.8 ± 7.3)% vs (79.4 ± 6.9)%, P = 0.037\\] compared with the other. In HLA-matched sibling HSCT setting, the presence of IFN-γ + 874 T allele in recipients or in both recipients and donors significantly decreased the risk of grade II-IV aGVHD and CMV infection and increased EFS. While IFN-γ + 874 A/A in donors or in both recipients and donors was associated with shorter duration to neutrophil recovery.

Effects of a novel SNP of IGF2R gene on growth traits and expression rate of IGF2R and IGF2 genes in gluteus medius muscle of Egyptian buffalo.

PubMed

El-Magd, Mohammed Abu; Abo-Al-Ela, Haitham G; El-Nahas, Abeer; Saleh, Ayman A; Mansour, Ali A

2014-05-01

Insulin-like growth factor 2 receptor (IGF2R) is responsible for degradation of the muscle development initiator, IGF2, and thus it can be used as a marker for selection strategies in the farm animals. The aim of this study was to search for polymorphisms in three coding loci of IGF2R, and to analyze their effect on the growth traits and on the expression levels of IGF2R and IGF2 genes in the gluteus medius muscle of Egyptian buffaloes. A novel A266C SNP was detected in the coding sequences of the third IGF2R locus (at nucleotide number 51 of exon 23) among Egyptian water buffaloes. This SNP was non-synonymous mutation and led to replacement of Y (tyrosine) amino acid (aa) by D (aspartic acid) aa. Three different single-strand conformation polymorphism patterns were observed in the third IGF2R locus: AA, AC, and CC with frequencies of 0.555, 0.195, and 0.250, respectively. Statistical analysis showed that the homozygous AA genotype significantly associated with the average daily gain than AC and CC genotypes from birth to 9 mo of age. Expression analysis showed that the A266C SNP was correlated with IGF2, but not with IGF2R, mRNA levels in the gluteus medius muscle of Egyptian buffaloes. The highest IGF2 mRNA level was estimated in the muscle of animals with the AA homozygous genotype as compared to the AC heterozygotes and CC homozygotes. We conclude that A266C SNP at nucleotide number 51 of exon 23 of the IGF2R gene is associated with the ADG during the early stages of life (from birth to 9 mo of age) and this effect is accompanied by, and may be caused by, increased expression levels of the IGF2 gene. Copyright © 2014 Elsevier B.V. All rights reserved.

Characterization of monoclonal antibodies against hepatitis C virus nonstructural protein 3: different antigenic determinants from human B cells.

PubMed

Ou-Yang, P; Chiang, B L; Hwang, L H; Chen, Y G; Yang, P M; Chi, W K; Chen, P J; Chen, D S

1999-04-01

The nonstructural (NS3) region protein of hepatitis C virus (HCV) possesses major B-cell epitopes that induce antibodies after infection. To elucidate further the characteristics of these B cells and their role in the immune regulation of HCV infection, T9 (portion of NS3 region, amino acids [a.a.] 1188-1493)-specific monoclonal antibodies were derived and mapped for B-cell antigenic determinants with recombinant proteins. A total of 10 T9-specific hybridomas were generated and tested for B-cell antigenic determinants. To analyze the B-cell antigenic determinants, eight recombinant proteins including NS3-e (a.a. 1175-1334), NS3-a' (a.a. 1175-1250), NS3-a (a.a. 1251-1334), NS3-b (a.a. 1323-1412), NS3-c (a.a. 1407-1499), NS3-a/b (a.a. 1251-1412), NS3-bc (a.a. 1323-1499), and NS3-abc (a.a. 1251-1499) encoded by NS3-region internal clones were expressed and tested for immunoblotting. The data suggested IgG hybridomas recognized NS3-a, NS3-a', or NS3-b protein by immunoblotting. By contrast, the NS3-e protein bears the major antigenic determinant recognized by human sera. Half of the hybridomas were found to react with protein NS3-a', which is not a major B-cell antigenic determinant in humans. These data suggested that conformational epitopes in vivo may be important for B-cell recognition.

Polymorphism of μ-Opioid Receptor Gene (OPRM1:c.118A>G) Might Not Protect against or Enhance Morphine-Induced Nausea or Vomiting

PubMed Central

Chen, Li-Kuei; Chen, Shiou-Sheng; Huang, Chi-Hsiang; Yang, Hong-Jyh; Lin, Chen-Jung; Chien, Kuo-Liong; Fan, Shou-Zen

2013-01-01

A cohort, double blind, and randomized study was conducted to investigate the effect of a single nucleotide polymorphism of the μ-opioid receptor at nucleotide position 118 (OPRM1:c.118A>G) on the association with the most common side effects (nausea or vomiting) induced by intravenous patient control analgesia (IVPCA) with morphine, including incidence and severity analysis. A total of 129 Taiwanese women undergoing gynecology surgery received IVPCA with pure morphine for postoperative pain relief. Blood samples were collected and sequenced with high resolution melting analysis to detect three different genotypes of OPRM1 (AA, AG, and GG). All candidates 24 h postoperatively will be interviewed to record the clinical phenotype with subjective complaints and objective observations. The genotyping after laboratory analysis showed that 56 women (43.4%) were AA, 57 (44.2%) were AG, and 16 (12.4%) were GG. The distribution of genotype did not violate Hardy-Weinberg equilibrium test. There was no significant difference neither between the severity and incidence of IVPCA morphine-induced side effects and genotype nor between the association between morphine consumption versus genotype. However, there was significant difference of the relation between morphine consumption and the severity and incidence of IVPCA morphine-induced nausea and vomiting. The genetic analysis for the severity and incidence of IVPCA morphine-induced nausea or vomiting showed no association between phenotype and genotype. It might imply that OPRM1:c.118A>G does not protect against IVPCA morphine-induced nausea or vomiting. PMID:23431434

Splicing-related single nucleotide polymorphism of RAB, member of RAS oncogene family like 2B (RABL2B) jeopardises semen quality in Chinese Holstein bulls.

PubMed

Wang, Xiuge; Cui, Xiaohui; Zhang, Yan; Hao, Haisheng; Ju, Zhihua; Liu, Deyu; Jiang, Qiang; Yang, Chunhong; Sun, Yan; Wang, Changfa; Huang, Jinming; Zhu, Huabin

2017-11-01

RAB, member of RAS oncogene family like 2B (RABL2B) is a member of a poorly characterised clade of the RAS GTPase superfamily, which plays an essential role in male fertility, sperm intraflagellar transport and tail assembly. In the present study, we identified a novel RABL2B splice variant in bovine testis and spermatozoa. This splice variant, designated RABL2B-TV, is characterised by exon 2 skipping. Moreover, a single nucleotide polymorphism (SNP), namely c.125G>A, was found within the exonic splicing enhancer (ESE) motif, indicating that the SNP caused the production of the RABL2B-TV aberrant splice variant. This was demonstrated by constructing a pSPL3 exon capturing vector with different genotypes and transfecting these vectors into murine Leydig tumour cell line (MLTC-1) cells. Expression of the RABL2B-TV transcript was lower in semen from high- versus low-performance bulls. Association analysis showed that sperm deformity rate was significantly lower in Chinese Holstein bulls with the GG or GA genotype than in bulls with the AA genotype (P<0.05). In addition, initial sperm motility was significantly higher in individuals with the GG or GA genotype than in individuals with the AA genotype (P<0.05). The findings of the present study suggest that the difference in semen quality in bulls with different RABL2B genotypes is generated via an alternative splicing mechanism caused by a functional SNP within the ESE motif.

Identification of three genotypes of sugarcane yellow leaf virus causing yellow leaf disease from India and their molecular characterization.

PubMed

Viswanathan, R; Balamuralikrishnan, M; Karuppaiah, R

2008-12-01

Sugarcane yellow leaf virus (SCYLV) that causes yellow leaf disease (YLD) in sugarcane (recently reported in India) belongs to Polerovirus. Detailed studies were conducted to characterize the virus based on partial open reading frames (ORFs) 1 and 2 and complete ORFs 3 and 4 sequences in their genome. Reverse-transcriptase polymerase chain reaction (RT-PCR) was performed on 48 sugarcane leaf samples to detect the virus using a specific set of primers. Of the 48 samples, 36 samples (field samples with and without foliar symptoms) including 10 meristem culture derived plants were found to be positive to SCYLV infection. Additionally, an aphid colony collected from symptomatic sugarcane in the field was also found to be SCYLV positive. The amplicons from 22 samples were cloned, sequenced and acronymed as SCYLV-CB isolates. The nucleotide (nt) and amino acid (aa) sequence comparison showed a significant variation between SCYLV-CB and the database sequences at nt (3.7-5.1%) and aa (3.2-5.3%) sequence level in the CP coding region. However, the database sequences comprising isolates of three reported genotypes, viz., BRA, PER and REU, were observed with least nt and aa sequence dissimilarities (0.0-1.6%). The phylogenetic analyses of the overlapping ORFs (ORF 3 and ORF 4) of SCYLV encoding CP and MP determined in this study and additional sequences of 26 other isolates including an Indian isolate (SCYLV-IND) available from GenBank were distributed in four phylogenetic clusters. The SCYLV-CB isolates from this study lineated in two clusters (C1 and C2) and all the other isolates from the worldwide locations into another two clusters (C3 and C4). The sequence variation of the isolates in this study with the database isolates, even in the least variable region of the SCYLV genome, showed that the population existing in India is significantly different from rest of the world. Further, comparison of partial sequences encoding for ORFs 1 and 2 revealed that YLD in sugarcane in India is caused by at least three genotypes, viz., CUB, IND and BRA-PER, of which a majority of the samples were found infected with Cuban genotype (CUB) and lesser by IND and BRA-PER genotypes. The genotype IND was identified as a new genotype from this study, and this was found to have significant variation with the reported genotypes.

Association of LIPC -250G>A polymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations

PubMed Central

2010-01-01

Background The association between -250G>A polymorphism in the promoter region of the hepatic lipase gene (LIPC) and plasma high-density lipoprotein cholesterol (HDL-C) concentration is contradictory in diverse ethnics. Bai Ku Yao is an isolated subgroup of the Yao minority in China. This study was designed to detect the association of LIPC -250G>A (rs2070895) polymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations. Methods A total of 778 subjects of Bai Ku Yao and 648 participants of Han Chinese aged 15-80 were randomly selected from our previous stratified randomized cluster samples. Genotyping of the LIPC -250G>A was performed by polymerse chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Results The levels of serum total cholesterol (TC), HDL-C, low-density lipoprotein cholesterol (LDL-C) and apolipoprotein (Apo) AI were lower in Bai Ku Yao than in Han (P < 0.01 for all). The frequencies of GG, GA and AA genotypes were 50.0%, 43.3% and 6.7% in Bai Ku Yao, and 35.7%, 50.6% and 13.7% in Han (P < 0.01); respectively. The frequencies of G and A alleles were 71.7% and 28.3% in Bai Ku Yao, and 61.0% and 39.0% in Han (P < 0.01). The levels of HDL-C and the ratio of ApoAI to ApoB in Bai Ku Yao were lower in GG genotype than in GA or AA genotype (P < 0.05-0.01). The levels of TC, HDL-C, LDL-C and ApoB in Han were lower in GG genotype than in GA or AA genotype (P < 0.05-0.01). The levels of HDL-C and the ratio of ApoAI to ApoB in Bai Ku Yao, and the levels of HDL-C, LDL-C and ApoB in Han were correlated with genotype and/or allele (P < 0.05 for all). Serum lipid parameters were also correlated with age, sex, alcohol consumption, cigarette smoking, blood pressure, body weight, and body mass index in both ethnic groups. Conclusions The differences in the serum lipid profiles between the two ethnic groups might partly result from different genotypic frequency of LIPC -250G>A or different LIPC-enviromental interactions. PMID:20222961

Genotypic and Antimicrobial Susceptibility of Carbapenem-resistant Acinetobacter baumannii: Analysis of ISAba Elements and blaOXA-23-like Genes Including a New Variant

PubMed Central

Bahador, Abbas; Raoofian, Reza; Pourakbari, Babak; Taheri, Mohammad; Hashemizadeh, Zahra; Hashemi, Farhad B.

2015-01-01

Carbapenem-resistant Acinetobacter baumannii (CR-AB) causes serious nosocomial infections, especially in ICU wards of hospitals, worldwide. Expression of blaOXA genes is the chief mechanism of conferring carbapenem resistance among CR-AB. Although some blaOXA genes have been studied among CR-AB isolates from Iran, their blaOXA-23-like genes have not been investigated. We used a multiplex-PCR to detect Ambler class A, B, and D carbapenemases of 85 isolates, and determined that 34 harbored blaOXA-23-like genes. Amplified fragment length polymorphism (AFLP) genotyping, followed by DNA sequencing of blaOXA-23-like amplicons of CR-AB from each AFLP group was used to characterize their blaOXA-23-like genes. We also assessed the antimicrobial susceptibility pattern of CR-AB isolates, and tested whether they harbored insertion sequences ISAba1 and ISAba4. Sequence comparison with reference strain A. baumannii (NCTC12156) revealed five types of mutations in blaOXA-23-like genes; including one novel variant and four mutants that were already reported from China and the USA. All of the blaOXA-23-like genes mutations were associated with increased minimum inhibitory concentrations (MICs) against imipenem. ISAba1 and ISAba4 sequences were detected upstream of blaOXA-23 genes in 19 and 7% of isolates, respectively. The isolation of CR-AB with new blaOXA-23 mutations including some that have been reported from the USA and China highlights CR-AB pervasive distribution, which underscores the importance of concerted national and global efforts to control the spread of CR-AB isolates worldwide. PMID:26617588

Interleukin-18 -607C/A gene polymorphism in Egyptian asthmatic children.

PubMed

Shaaban, Hala Hamdi; Mohy, Abeer Mohamed; Abdel-Razek, Abdel-Rahman Ahmed; Wahab, Amira Abdel

2014-08-01

Asthma is a multifactorial respiratory disease determined by interactions of multiple disease susceptibility genes and environmental factors. Interleukin (IL)-18 is an important cytokine for initiating and perpetuating the catabolic and inflammatory response in allergic asthma. A number of single nucleotide polymorphisms that influence IL-18 production are found in the gene promoter region. The aim of this study was to investigate the association of IL-18 -607C/A promoter polymorphism with asthma and whether this polymorphism influenced the severity of asthma in affected children. The influence of this promoter gene polymorphism on total serum IgE level in studied subjects was also investigated. This study was carried out at the Allergy Clinic of Abu El Reesh Children's Hospital at Cairo University, Egypt. This study included 40 asthmatic children, subdivided into four groups according to different degrees of asthma severity, and 20 apparently healthy subjects as the control group. All cases were subjected to history taking, clinical examination, and the following laboratory investigations: complete blood count, total serum IgE level assay by ELISA and genomic DNA extraction, and analysis for IL-18 -607C/A promoter gene polymorphism using the PCR-RFLP (restriction fragment length polymorphism) technique. In the present study the IL-18 -607AA genotype frequency was higher in cases (22.5 %) than in the control group (15 %); however, the difference was not statistically significant (p = 0.773). No statistically significant difference between the degree of asthma severity and IL-18 -607C/A polymorphism was found (p = 0.489). No significant association could be detected upon comparing the frequencies of C and A alleles among the two studied groups (p = 0.366). Also, no significant differences were demonstrated for the allele frequencies when the intermittent with mild [odds ratio (OR) = 2.72, 95 % CI 1.03-2.33, p = 0.067], intermittent with moderate, and severe (OR = 2.8, 95 % CI 1.01-8.5, p = 0.066) asthma groups were compared. The median value of the total serum IgE level in asthmatic cases with the mutant genotype (AA) was significantly higher [360 IU/L (96.6-1,340 IU/L)] than in the control group [119 IU/L (70.6-158.9 IU/L)] (p = 0.033). No significant statistical difference was encountered regarding the distribution of IL-18 -607C/A genotypes and allele frequencies in asthma patients and healthy controls. Also, there were no significant associations between asthma severity and different genotypes or alleles. The median value of the total serum IgE level in asthmatic cases with the mutant genotype (AA) was significantly higher than in the control group. Thus, IL-18 -607AA genotype frequency might be related to higher total serum IgE.

HicA of Escherichia coli defines a novel family of translation-independent mRNA interferases in bacteria and archaea.

PubMed

Jørgensen, Mikkel G; Pandey, Deo P; Jaskolska, Milena; Gerdes, Kenn

2009-02-01

Toxin-antitoxin (TA) loci are common in free-living bacteria and archaea. TA loci encode a stable toxin that is neutralized by a metabolically unstable antitoxin. The antitoxin can be either a protein or an antisense RNA. So far, six different TA gene families, in which the antitoxins are proteins, have been identified. Recently, Makarova et al. (K. S. Makarova, N. V. Grishin, and E. V. Koonin, Bioinformatics 22:2581-2584, 2006) suggested that the hicAB loci constitute a novel TA gene family. Using the hicAB locus of Escherichia coli K-12 as a model system, we present evidence that supports this inference: expression of the small HicA protein (58 amino acids [aa]) induced cleavage in three model mRNAs and tmRNA. Concomitantly, the global rate of translation was severely reduced. Using tmRNA as a substrate, we show that HicA-induced cleavage does not require the target RNA to be translated. Expression of HicB (145 aa) prevented HicA-mediated inhibition of cell growth. These results suggest that HicB neutralizes HicA and therefore functions as an antitoxin. As with other antitoxins (RelB and MazF), HicB could resuscitate cells inhibited by HicA, indicating that ectopic production of HicA induces a bacteriostatic rather than a bactericidal condition. Nutrient starvation induced strong hicAB transcription that depended on Lon protease. Mining of 218 prokaryotic genomes revealed that hicAB loci are abundant in bacteria and archaea.

Practical Application of Finite Element Analysis to Aircraft Structural Design

DTIC Science & Technology

1986-08-01

at the design stage AEROELASTICITE ET OPTIMISATION EN AVANT-PROJET (AA)PETIAU, C; (AB) BOUTIN , D. Avions Marcel Dassault-Breguet Aviation, Saint...Interscience, 1981, p. 431-443. 810000 p. 13 refs 8 In: EN (English) p. 2018 The design complexity and size of convectively-cooled engine and airframe

Comparing Genomes in Terms of Protein Structure: Surveys of a Finite Parts List

DTIC Science & Technology

1998-01-01

539-547. 39. Fraser, C M, et al. (1997) Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi [see comments]. Nature 390, 580-586. 40...Methanobacterium thermoautotrophicum [202] BS Bacillus subtilis [203] AB Archaeoglobus fulgidus [204] BB Borrelia burgdorferi [39] AA Aquifex aeolicus

Serum Markers of Neurodegeneration in Maple Syrup Urine Disease.

PubMed

Scaini, Giselli; Tonon, Tássia; de Souza, Carolina F Moura; Schuk, Patricia F; Ferreira, Gustavo C; Neto, Joao Seda; Amorin, Tatiana; Schwartz, Ida Vanessa D; Streck, Emilio L

2017-09-01

Maple syrup urine disease (MSUD) is an inherited disorder caused by deficient activity of the branched-chain α-keto acid dehydrogenase complex involved in the degradation pathway of branched-chain amino acids (BCAAs) and their respective α-keto-acids. Patients affected by MSUD present severe neurological symptoms and brain abnormalities, whose pathophysiology is poorly known. However, preclinical studies have suggested alterations in markers involved with neurodegeneration. Because there are no studies in the literature that report the neurodegenerative markers in MSUD patients, the present study evaluated neurodegenerative markers (brain-derived neurotrophic factor (BDNF), cathepsin D, neural cell adhesion molecule (NCAM), plasminogen activator inhibitor-1 total (PAI-1 (total)), platelet-derived growth factor AA (PDGF-AA), PDGF-AB/BB) in plasma from 10 MSUD patients during dietary treatment. Our results showed a significant decrease in BDNF and PDGF-AA levels in MSUD patients. On the other hand, NCAM and cathepsin D levels were significantly greater in MSUD patients compared to the control group, while no significant changes were observed in the levels of PAI-1 (total) and PDGF-AB/BB between the control and MSUD groups. Our data show that MSUD patients present alterations in proteins involved in the neurodegenerative process. Thus, the present findings corroborate previous studies that demonstrated that neurotrophic factors and lysosomal proteases may contribute, along with other mechanisms, to the intellectual deficit and neurodegeneration observed in MSUD.

Binding and Diffusion of Lithium in Graphite: Quantum Monte Carlo Benchmarks and Validation of van der Waals Density Functional Methods

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ganesh, P.; Kim, Jeongnim; Park, Changwon

2014-11-03

In highly accurate diffusion quantum Monte Carlo (QMC) studies of the adsorption and diffusion of atomic lithium in AA-stacked graphite are compared with van der Waals-including density functional theory (DFT) calculations. Predicted QMC lattice constants for pure AA graphite agree with experiment. Pure AA-stacked graphite is shown to challenge many van der Waals methods even when they are accurate for conventional AB graphite. Moreover, the highest overall DFT accuracy, considering pure AA-stacked graphite as well as lithium binding and diffusion, is obtained by the self-consistent van der Waals functional vdW-DF2, although errors in binding energies remain. Empirical approaches based onmore » point charges such as DFT-D are inaccurate unless the local charge transfer is assessed. Our results demonstrate that the lithium carbon system requires a simultaneous highly accurate description of both charge transfer and van der Waals interactions, favoring self-consistent approaches.« less

Detection and genetic characterization of bovine kobuvirus from calves in Egypt.

PubMed

Mohamed, Fakry F; Mansour, Shimaa M G; Orabi, Ahmed; El-Araby, Iman E; Ng, Terry Fei Fan; Mor, Sunil K; Goyal, Sagar M

2018-06-01

Kobuviruses are small non-enveloped RNA viruses that probably cause diarrhea in cattle and swine. Since its discovery in 2003, few studies have addressed bovine kobuvirus (BKoV; a species of Aichivirus B) infections. BKoV has been reported in Europe, Asia, and South America, suggesting a worldwide distribution. To investigate the presence of BKoV in Egypt, 36 fecal specimens from diarrheic calves in two different Egyptian provinces (Cairo and Sharkia) were screened by RT-PCR and 24 (66.7%) were found positive for BKoV. RNA from one of the positive samples (BKoV/Egy-1/KY407744) was subjected to next-generation sequencing to determine the complete BKoV genome sequence. When compared to the only recorded BKoV genome sequence (BKoV/U-1/AB084788), the studied strain showed 94 amino acid (aa) substitutions through its entire polyprotein (2463 aa), one nucleotide (nt) insertion and one nt deletion in the 2B gene and 4-nt deletions in the UTRs (2 each). Additionally, five VP1 and seven 3D sequences were obtained from other samples by using RT-PCR and Sanger sequencing. A discrepancy in the phylogenetic topography of VP1 and 3D was observed, where the Egyptian VP1 sequences were classified as a distinct cluster within the proposed lineage 1 (genotype A), which also contained strains from the UK, Brazil, and Japan. While, the 3D sequences from Cairo were related to those of Chinese strains unlike Sharkia ones that were more closer to Korean  strains. To the best of our knowledge, this is the first detection and genomic characterization of BKoV in Egypt or indeed Africa.

Association between interleukin 10 gene polymorphisms and risk of type 2 diabetes mellitus in a Chinese population.

PubMed

Bai, Hua; Jing, Danqing; Guo, Aitao; Yin, Shinan

2014-06-01

To investigate the relationship between the interleukin 10 (IL10) gene single nucleotide polymorphisms (SNP) -1082 G/A (rs1800896), -819 T/C (rs1800871) and -592 A/C (rs1800872) and risk of type 2 diabetes mellitus in a Chinese population. This case-control study recruited patients with type 2 diabetes mellitus and healthy control subjects. Genotyping of the -1082 G/A (rs1800896), -819 T/C (rs1800871) and -592 A/C (rs1800872) SNPs was conducted and genotype frequencies were compared between the two groups. The study recruited 364 patients with type 2 diabetes mellitus and 677 healthy controls. Patients carrying the -1082 GG genotype had a significantly increased risk of type 2 diabetes mellitus (adjusted odds ratio [OR] 1.57, 95% confidence interval [CI] 1.03, 2.68), as did those patients carrying the -592 AA genotype (adjusted OR 1.63, 95% CI 1.06, 2.53). Subjects carrying both the -1082 GA + GG and -592 AC + AA genotypes had a significantly increased risk of type 2 diabetes mellitus (adjusted OR 2.03, 95% CI 1.24, 3.15). The SNPs -1082G/A and -592 A/C increased the risk for type 2 diabetes mellitus, and could be potential targets for screening for the early detection of the risk of type 2 diabetes mellitus. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Study of single nucleotide polymorphisms of FBW7 and its substrate genes revealed a predictive factor for paclitaxel plus cisplatin chemotherapy in Chinese patients with advanced esophageal squamous cell carcinoma.

PubMed

Liu, Ying; Xu, Shu Ning; Chen, Yong Shun; Wu, Xiao Yuan; Qiao, Lei; Li, Ke; Yuan, Long

2016-07-12

Paclitaxel plays a major role in the treatment of advanced esophageal squamous cell carcinoma. However, there is no biomarker that could be used to predict the clinical response of paclitaxel. This work was conducted to investigate the association of genetic polymorphisms in FBW7 and its substrate genes and the clinical response of paclitaxel. Patients with advanced esophageal squamous cell carcinoma were treated with paclitaxel 175 mg/m2 over 3 hours day 1 and cisplatin 75 mg/m2 day 1, every 3 weeks. The genotypes of 11 FBW7 and its substrate gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Statistical analysis revealed that patients with mTOR rs1057079 AG (ORadjusted: 4.59; 95% CI: 1.78-11.86) genotype had significant correlation with the clinical response of paclitaxel when compared with AA genotype after adjustment for sex, age, and chemotherapy cycle. The median progression-free survival (PFS) of patients with advanced ESCC who received paclitaxel plus cisplatin (TP) as first-line treatment is 14.3 months (95% CI: 9.0-19.60 months). The median PFS (mPFS) of AG genotypes and AA genotypes in mTOR rs1057079 were 17.31 months (95% CI: 15.9-18.67 months) and 9.8 months (95% CI: 8.58-11.02 months) (p=0.019), respectively.

Polymorphism of SLC25A32, the folate transporter gene, is associated with plasma folate levels and bone fractures in Japanese postmenopausal women.

PubMed

Urano, Tomohiko; Shiraki, Masataka; Saito, Mitsuru; Sasaki, Noriko; Ouchi, Yasuyoshi; Inoue, Satoshi

2014-10-01

Elevation of homocysteine is associated with an increased risk for bone fractures. We previously reported that the methylenetetrahydrofolate reductase (MTHFR) gene polymorphism is associated with homocysteine levels and fracture. The association between the fracture and folate levels or their related gene polymorphisms is not completely clear. We speculated that the SLC25A32 gene, the mitochondrial inner membrane folate transporter, also could be implicated in the regulation of folate metabolism and fracture. A total of 851 Japanese postmenopausal women participated in the association study between the single nucleotide polymorphism genotype and plasma homocysteine or folate. We also tested the association between the candidate single nucleotide polymorphism and 663 postmenopausal women. The AA genotype of rs2241777 single nucleotide polymorphism at the 3'UTR region in the SLC25A32 gene was associated with lower plasma folate concentration compared with the other genotypes in 851 postmenopausal women. A total of 674 postmenopausal ambulatory Japanese women were followed up for 5.5 ± 0.1 years (mean ± SE). The AA genotype groups also showed an apparently higher rate and earlier onset of incident fractures than the other genotypes. A total of 407 participants had >70% young-adult mean bone mineral density at the start of the observation. These results show that the SLC25A32 gene polymorphism could be a risk factor for lower folate concentration and future fracture. © 2013 Japan Geriatrics Society.

Association of matrix metalloproteinase-7 (-181A/G) promoter polymorphism in chronic pancreatitis.

PubMed

Manjari, K Sri; Jyothy, A; Kumar, P Shravan; Prabhakar, B; Nallari, Pratibha; Venkateshwari, A

2014-11-01

Chronic pancreatitis is progressive and irreversible destruction of the pancreas. Matrix metalloproteinase-7 (MMP-7) is a secreted matrilysin, which contributes to angiogenesis and breakdown of basement membranes of pancreatic tissues. The present study was aimed to investigate the association of MMP-7 -181A/G (rs11568818) gene promoter polymorphism in patients with chronic pancreatitis. A total of 100 chronic pancreatitis patients and 150 unrelated healthy individuals were included in this case control study. The genotyping of the MMP-7 gene (- 181 A/G) (rs11568818) was carried out based on PCR-RFLP. The serum levels of MMP-7 were determined by ELISA. Association between genotypes and chronic pancreatitis was examined by odds ratio (OR) with 95% confidence interval (CI). The frequencies of the genotypes in promoter of MMP-7 were AA 49 per cent, AG 25 per cent and GG 26 per cent in chronic pancreatitis patients and AA 53 per cent, AG 38 per cent and GG 9 per cent in control subjects. Frequency of MMP-7 -181GG genotype and - 181G allele was significantly associated with chronic pancreatitis compared to healthy subjects [OR = 1.58 (95% CI: 1.06 -2.36), p =0.019]. There was no significant difference in the serum MMP-7 levels in the patients compared to control subjects. The present study revealed a significant association of MMP-7 -181A/G (rs11568818) GG genotype with chronic pancreatitis patients, indicating its possible association with the disease.

Effect of epidermal growth factor receptor gene polymorphisms on prognosis in glioma patients

PubMed Central

Li, Jingjie; Yan, Mengdan; Xie, Zhilan; Zhu, Yuanyuan; Chen, Chao; Jin, Tianbo

2016-01-01

Previous studies suggested that single nucleotide polymorphisms (SNPs) in epidermal growth factor receptor (EGFR) are associated with risk of glioma. However, the associations between these SNPs and glioma patient prognosis have not yet been fully investigated. Therefore, the present study was aimed to evaluate the effects of EGFR polymorphisms on the glioma patient prognosis. We retrospectively evaluated 269 glioma patients and investigated associations between EGFR SNPs and patient prognosis using Cox proportional hazard models and Kaplan-Meier curves. Univariate analysis revealed that age, gross-total resection and chemotherapy were associated with the prognosis of glioma patients (p < 0.05). In addition, four EGFR SNPs (rs11506105, rs3752651, rs1468727 and rs845552) correlated with overall survival (OS) (Log-rank p = 0.011, 0.020, 0.008, and 0.009, respectively) and progression-free survival PFS (Log-rank p = 0.026, 0.024, 0.019 and 0.009, respectively). Multivariate analysis indicated that the rs11506105 G/G genotype, the rs3752651 and rs1468727 C/C genotype and the rs845552 A/A genotype correlated inversely with OS and PFS. In addition, OS among patients with the rs730437 C/C genotype (p = 0.030) was significantly lower OS than among patients with A/A genotype. These data suggest that five EGFR SNPs (rs11506105, rs3752651, rs1468727, rs845552 and rs730437) correlated with glioma patient prognosis, and should be furthered validated in studies of ethnically diverse patients. PMID:27437777

Possible effect of norepinephrine transporter polymorphisms on methylphenidate-induced changes in neuropsychological function in attention-deficit hyperactivity disorder.

PubMed

Park, Subin; Kim, Jae-Won; Yang, Young-Hui; Hong, Soon-Beom; Park, Min-Hyeon; Kim, Boong-Nyun; Shin, Min-Sup; Yoo, Hee-Jeong; Cho, Soo-Churl

2012-05-16

Dysregulation of noradrenergic system may play important roles in pathophysiology of attention-deficit/hyperactivity disorder (ADHD). We examined the relationship between polymorphisms in the norepinephrine transporter SLC6A2 gene and attentional performance before and after medication in children with ADHD. Fifty-three medication-naïve children with ADHD were genotyped and evaluated using the continuous performance test (CPT). After 8-weeks of methylphenidate treatment, these children were evaluated by CPT again. We compared the baseline CPT measures and the post-treatment changes in the CPT measures based on the G1287A and the A-3081T polymorphisms of SLC6A2. There was no significant difference in the baseline CPT measures associated with the G1287A or A-3081T polymorphisms. After medication, however, ADHD subjects with the G/G genotype at the G1287A polymorphism showed a greater decrease in the mean omission error scores (p = 0.006) than subjects with the G/A or A/A genotypes, and subjects with the T allele at the A-3081T polymorphism (T/T or A/T) showed a greater decrease in the mean commission error scores (p = 0.003) than those with the A/A genotypes. Our results provide evidence for the possible role of the G1287A and A-3081T genotypes of SLC6A2 in methylphenidate-induced improvement in attentional performance and support the noradrenergic hypothesis for the pathophysiology of ADHD.

Genetic association between human chitinases and lung function in COPD.

PubMed

Aminuddin, F; Akhabir, L; Stefanowicz, D; Paré, P D; Connett, J E; Anthonisen, N R; Fahy, J V; Seibold, M A; Burchard, E G; Eng, C; Gulsvik, A; Bakke, P; Cho, M H; Litonjua, A; Lomas, D A; Anderson, W H; Beaty, T H; Crapo, J D; Silverman, E K; Sandford, A J

2012-07-01

Two primary chitinases have been identified in humans--acid mammalian chitinase (AMCase) and chitotriosidase (CHIT1). Mammalian chitinases have been observed to affect the host's immune response. The aim of this study was to test for association between genetic variation in the chitinases and phenotypes related to chronic obstructive pulmonary disease (COPD). Polymorphisms in the chitinase genes were selected based on previous associations with respiratory diseases. Polymorphisms that were associated with lung function level or rate of decline in the Lung Health Study (LHS) cohort were analyzed for association with COPD affection status in four other COPD case-control populations. Chitinase activity and protein levels were also related to genotypes. In the caucasian LHS population, the baseline forced expiratory volume in one second (FEV(1)) was significantly different between the AA and GG genotypic groups of the AMCase rs3818822 polymorphism. Subjects with the GG genotype had higher AMCase protein and chitinase activity compared with AA homozygotes. For CHIT1 rs2494303, a significant association was observed between rate of decline in FEV(1) and the different genotypes. In the African American LHS population, CHIT1 rs2494303 and AMCase G339T genotypes were associated with rate of decline in FEV(1). Although a significant effect of chitinase gene alleles was found on lung function level and decline in the LHS, we were unable to replicate the associations with COPD affection status in the other COPD study groups.

Contribution of Matrix Metalloproteinase-7 Genotypes to the Risk of Non-solid Tumor, Childhood Leukemia.

PubMed

Pei, Jen-Sheng; Chou, An-Kuo; Hsu, Pei-Chen; Tsai, Chia-Wen; Chang, Wen-Shin; Wu, Meng-Feng; Wu, Ming-Hsien; Hsia, Te-Chun; Cheng, Shun-Ping; Bau, DA-Tian

2017-12-01

The matrix metalloproteinases (MMPs) are important in inflammation and carcinogenesis, and the genotypic role of MMP7 has never been examined in leukemia to date. Therefore, in this study we aimed to evaluate the contribution of the genotypic variants in the promoter region of MMP7 (A-181G and C-153T) to childhood acute lymphoblastic leukemia (ALL) risk in Taiwan. In this case-control study, 266 patients with childhood ALL and 266 non-cancer controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism methodology. The distribution of AA, AG and GG for MMP7 promoter A-181G genotype was 83.5, 12.0 and 4.5% in the childhood ALL group and 89.8%, 9.4 and 0.8% in the non-cancer control group, respectively (p for trend=0.0134), significantly differentially distributed between childhood ALL and control groups. The comparisons in allelic frequency distribution also support the findings that G appears to be the risky allele in childhood ALL. In genotype and gender interaction analysis, it was found that boys carrying the MMP7 A-181G GG and AG+GG genotypes had 9.05- and 2.45-fold odds ratios (ORs) (p=0.0135 and 0.0142, respectively) for childhood ALL compared to those carrying wild-type AA genotype. But these differences were not found in girls. Analysis of genotype interaction with age of onset age showed those aged less than 3.5 years at onset carrying the GG or AG+GG genotypes also had elevated ORs of 8.79- and 2.04-fold (p=0.0150 and 0.0413, respectively) for childhood ALL, but there was no such difference for those having an age at onset of 3.5 years or more. Our results indicate that the MMP7 A-181G genotype interacts with age and gender and may serve as an early and predictive biomarker for childhood ALL. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Decreasing racial disparity with the combination of ledipasvir-sofosbuvir for the treatment of chronic hepatitis C.

PubMed

Naylor, Paul H; Mutchnick, Milton

2017-01-01

African Americans (AA) in the US are twice as likely to be infected with hepatitis C virus (HCV) compared to the non-Hispanic-white US population (Cau). They are also more likely to be infected with HCV genotype 1, more likely to develop hepatocellular carcinoma, and, in addition, have a lower response rate to interferon-based therapies. With the increase in response rates reported for combinations of direct-acting antivirals, the possibility that racial disparity would be eliminated by agents that directly inhibit virus replication has become a reality. The objective of this review is to evaluate the literature from clinical studies and retrospective analysis with respect to the response of AA to the most prescribed antiviral combination sofosbuvir plus ledipasvir. While few studies have focused on AA patients, sufficient information is availed from the literature and studies in our predominately AA clinic population to confirm that ledipasvir-sofosbuvir has a similar effectiveness in AA as compared to Cau.

The CYP1A2 -163C>A polymorphism does not alter the effects of caffeine on basketball performance

PubMed Central

Puente, Carlos; Abián-Vicén, Javier; Lara, Beatriz; Salinero, Juan José

2018-01-01

Purpose The aim of this investigation was to analyze the influence of the genetic variations of the -163C>A polymorphism of the CYP1A2 gene on the ergogenic effects of caffeine in elite basketball players. Methods Nineteen elite basketball players (10 men and 9 women) ingested 3 mg⋅kg-1 of caffeine or a placebo 60 min before performing 10 repetitions of the following series: the Abalakov jump test followed by the Change-of-Direction and Acceleration Test (CODAT). The players then competed in a 20-min simulated basketball game. Self-perceived performance and side effects were recorded by questionnaires after the trials. The effects of caffeine on basketball performance were established according to players’ CYP1A2 genotype (rs762551): AA homozygotes (n = 10) and C-allele carriers (n = 9). Results In the 10 repetitions, caffeine increased Abalakov jump height by a mean of 2.9±3.6% in AA homozygotes (p = 0.03) while this effect did not reach statistical significance for C-allele carriers (2.3 ± 6.8%; p = 0.33). Caffeine did not affect sprint time in the CODAT test in either genotype group but it increased the number of impacts performed during the simulated game in both AA homozygotes (4.1 ± 5.3%; p = 0.02) and C-allele carriers (3.3 ± 3.2%; p = 0.01). During the 24 h following the test, AA homozygotes tended to experience increased insomnia with caffeine while C-allele carriers did not present this effect. The remaining variables were unaffected by the genotype. Conclusion The CYP1A2 -163C>A polymorphism minimally altered the ergogenicity derived from the consumption of a moderate dose of caffeine in elite basketball players. PMID:29668752

Gene polymorphisms and febrile neutropenia in acute leukemia--no association with IL-4, CCR-5, IL-1RA, but the MBL-2, ACE, and TLR-4 are associated with the disease in Turkish patients: a preliminary study.

PubMed

Pehlivan, Mustafa; Sahin, Handan Haydaroğlu; Ozdilli, Kurşat; Onay, Hüseyin; Ozcan, Ali; Ozkinay, Ferda; Pehlivan, Sacide

2014-07-01

The aim of this study was to investigate the mannose-binding lectin 2 (MBL-2), interleukin (IL)-4, Toll-like receptor 4 (TLR-4), angiotensin converting enzyme (ACE), chemokine receptor 5 (CCR-5), and IL-1 receptor antagonist (RA) gene polymorphisms (GPs) in acute leukemias (ALs) and to evaluate their roles in febrile neutropenia (FN) resulting from chemotherapy. The study included 60 AL patients hospitalized between the period of July 2001 and August 2006. Polymorphisms for the genes ACE(I/D), CCR-5, IL-1RA, MBL-2, TLR-4, and IL-4 were typed by polymerase chain reaction (PCR) and/or PCR-restriction fragment length polymerase. Genotype frequencies for these genes were compared in the patient and control groups. The relationships between the genotypes and the body distribution of infections, pathogens, the duration of neutropenia, and febrile episodes in AL patients were evaluated. No significant differences in either the genotype distribution or the allelic frequencies of TLR-4, IL-4, CCR-5, IL-1RN GPs were observed between patients and healthy controls. The AB/BB genotype (53.3%) in the MBL-2 gene was found to be significantly higher in the AL patients compared with control groups. There were correlations between the presence of MBL-2, TLR-4, and ACE polymorphisms and clinical parameters due to FN. Overall, bacteremia was more common in MBL BB and ACE DD. Gram-positive bacteremia was more common in ACE for ID versus DD genotype. Gram-negative bacteremia was more common for both the MBL-2 AB/BB genotype and TLR-4 AG genotype. Median durations of febrile episodes were significantly shorter in ACE DD and MBL AB/BB. Although TLR-4, ACE, and MBL-2 GPs have been extensively investigated in different clinical pictures, this is the first study to evaluate the role of these polymorphisms in the genetic etiopathogenesis of FN in patients with ALs. As a conclusion, TLR-4, ACE, and MBL-2 genes might play roles in the genetic etiopathogenesis of FN in patients with ALs.

Hemagglutinin-specific neutralization of subacute sclerosing panencephalitis viruses

PubMed Central

Muller, Claude P.; Russell, Stephen J.

2018-01-01

Subacute sclerosing panencephalitis (SSPE) is a progressive, lethal complication of measles caused by particular mutants of measles virus (MeV) that persist in the brain despite high levels of neutralizing antibodies. We addressed the hypothesis that antigenic drift is involved in the pathogenetic mechanism of SSPE by analyzing antigenic alterations in the MeV envelope hemagglutinin protein (MeV-H) found in patients with SSPE in relation to major circulating MeV genotypes. To this aim, we obtained cDNA for the MeV-H gene from tissue taken at brain autopsy from 3 deceased persons with SSPE who had short (3–4 months, SMa79), average (3.5 years, SMa84), and long (18 years, SMa94) disease courses. Recombinant MeVs with a substituted MeV-H gene were generated by a reverse genetic system. Virus neutralization assays with a panel of anti-MeV-H murine monoclonal antibodies (mAbs) or vaccine-immunized mouse anti-MeV-H polyclonal sera were performed to determine the antigenic relatedness. Functional and receptor-binding analysis of the SSPE MeV-H showed activity in a SLAM/nectin-4–dependent manner. Similar to our panel of wild-type viruses, our SSPE viruses showed an altered antigenic profile. Genotypes A, G3, and F (SSPE case SMa79) were the exception, with an intact antigenic structure. Genotypes D7 and F (SSPE SMa79) showed enhanced neutralization by mAbs targeting antigenic site IIa. Genotypes H1 and the recently reported D4.2 were the most antigenically altered genotypes. Epitope mapping of neutralizing mAbs BH015 and BH130 reveal a new antigenic site on MeV-H, which we designated Φ for its intermediate position between previously defined antigenic sites Ia and Ib. We conclude that SSPE-causing viruses show similar antigenic properties to currently circulating MeV genotypes. The absence of a direct correlation between antigenic changes and predisposition of a certain genotype to cause SSPE does not lend support to the proposed antigenic drift as a pathogenetic mechanism in SSPE. PMID:29466428

Hemagglutinin-specific neutralization of subacute sclerosing panencephalitis viruses.

PubMed

Muñoz-Alía, Miguel Ángel; Muller, Claude P; Russell, Stephen J

2018-01-01

Subacute sclerosing panencephalitis (SSPE) is a progressive, lethal complication of measles caused by particular mutants of measles virus (MeV) that persist in the brain despite high levels of neutralizing antibodies. We addressed the hypothesis that antigenic drift is involved in the pathogenetic mechanism of SSPE by analyzing antigenic alterations in the MeV envelope hemagglutinin protein (MeV-H) found in patients with SSPE in relation to major circulating MeV genotypes. To this aim, we obtained cDNA for the MeV-H gene from tissue taken at brain autopsy from 3 deceased persons with SSPE who had short (3-4 months, SMa79), average (3.5 years, SMa84), and long (18 years, SMa94) disease courses. Recombinant MeVs with a substituted MeV-H gene were generated by a reverse genetic system. Virus neutralization assays with a panel of anti-MeV-H murine monoclonal antibodies (mAbs) or vaccine-immunized mouse anti-MeV-H polyclonal sera were performed to determine the antigenic relatedness. Functional and receptor-binding analysis of the SSPE MeV-H showed activity in a SLAM/nectin-4-dependent manner. Similar to our panel of wild-type viruses, our SSPE viruses showed an altered antigenic profile. Genotypes A, G3, and F (SSPE case SMa79) were the exception, with an intact antigenic structure. Genotypes D7 and F (SSPE SMa79) showed enhanced neutralization by mAbs targeting antigenic site IIa. Genotypes H1 and the recently reported D4.2 were the most antigenically altered genotypes. Epitope mapping of neutralizing mAbs BH015 and BH130 reveal a new antigenic site on MeV-H, which we designated Φ for its intermediate position between previously defined antigenic sites Ia and Ib. We conclude that SSPE-causing viruses show similar antigenic properties to currently circulating MeV genotypes. The absence of a direct correlation between antigenic changes and predisposition of a certain genotype to cause SSPE does not lend support to the proposed antigenic drift as a pathogenetic mechanism in SSPE.

Nanocarbon: Defect Architectures and Properties

NASA Astrophysics Data System (ADS)

Vuong, Amanda

The allotropes of carbon make its solid phases amongst the most diverse of any element. It can occur naturally as graphite and diamond, which have very different properties that make them suitable for a wide range of technological and commercial purposes. Recent developments in synthetic carbon include Highly Oriented Pyrolytic Graphite (HOPG) and nano-carbons, such as fullerenes, nanotubes and graphene. The main industrial application of bulk graphite is as an electrode material in steel production, but in purified nuclear graphite form, it is also used as a moderator in Advanced Gas-cooled Reactors across the United Kingdom. Both graphene and graphite are damaged over time when subjected to bombardment by electrons, neutrons or ions, and these have a wide range of effects on their physical and electrical properties, depending on the radiation flux and temperature. This research focuses on intrinsic defects in graphene and dimensional change in nuclear graphite. The method used here is computational chemistry, which complements physical experiments. Techniques used comprise of density functional theory (DFT) and molecular dynamics (MD), which are discussed in chapter 2 and chapter 3, respectively. The succeeding chapters describe the results of simulations performed to model defects in graphene and graphite. Chapter 4 presents the results of ab initio DFT calculations performed to investigate vacancy complexes that are formed in AA stacked bilayer graphene. In AB stacking, carbon atoms surrounding the lattice vacancies can form interlayer structures with sp2 bonding that are lower in energy compared to in-plane reconstructions. From the investigation of AA stacking, sp2 interlayer bonding of adjacent multivacancy defects in registry creates a type of stable sp2 bonded wormhole between the layers. Also, a new class of mezzanine structure characterised by sp3 interlayer bonding, resembling a prismatic vacancy loop has also been identified. The mezzanine, which is a V6 hexavacancy variant, where six sp3 carbon atoms sit midway between two carbon layers and bond to both, is substantially more stable than any other vacancy aggregate in AA stacked layers. Chapter 5 presents the results of ab initio DFT calculations performed to investigate the wormhole and mezzanine defect that were identified in chapter 4 and the ramp defect discovered by Trevethan et al.. DFT calculations were performed on these defects in twisted bilayer graphene. From the investigation of vacancy complexes in twisted bilayer graphene, it is found that vacancy complexes are unstable in the twisted region and are more favourable in formation energy when the stacking arrangement is close to AA or AB stacking. It has also been discovered that the ramp defect is more stable in the twisted bilayer graphene compared to the mezzanine defect. Chapter 6 presents the results of ab initio DFT calculations performed to investigate a form of extending defect, prismatic edge dislocation. Suarez-Martinez et al.'s research suggest the armchair core is disconnected from any other layer, whilst the zigzag core is connected. In the investigation here, the curvature of the mezzanine defect allows it to swing between the armchair, zigzag and Klein in the AA stacking. For the AB stacking configuration, the armchair and zigzag core are connected from any other layer. Chapter 7 present results of MD simulations using the adaptive intermolecular reactive empirical bond order (AIREBO) potential to investigate the dimensional change of graphite due to the formation of vacancies present in a single crystal. It has been identified that there is an expansion along the c-axis, whilst a contraction along the a- and b- axes due to the coalescence of vacancy forming in-plane and between the layers. The results here are in good agreement with experimental studies of low temperature irradiation. The final chapter gives conclusions to this work.

Association between CYP2E1 polymorphisms and risk of differentiated thyroid carcinoma.

PubMed

Pellé, Lucia; Cipollini, Monica; Tremmel, Roman; Romei, Cristina; Figlioli, Gisella; Gemignani, Federica; Melaiu, Ombretta; De Santi, Chiara; Barone, Elisa; Elisei, Rossella; Seiser, Eric; Innocenti, Federico; Zanger, Ulrich M; Landi, Stefano

2016-12-01

Differentiated thyroid carcinoma (DTC) results from complex interactions between genetic and environmental factors. Known etiological factors include exposure to ionizing radiations, previous thyroid diseases, and hormone factors. It has been speculated that dietary acrylamide (AA) formed in diverse foods following the Maillard's reaction could be a contributing factor for DTC in humans. Upon absorption, AA is biotransformed mainly by cytochrome P450 2E1 (CYP2E1) to glycidamide (GA). Considering that polymorphisms within CYP2E1 were found associated with endogenous levels of AA-Valine and GA-Valine hemoglobin adducts in humans, we raised the hypothesis that specific CYP2E1 genotypes could be associated with the risk of DTC. Analysis of four haplotype tagging SNPs (ht-SNPs) within the locus in a discovery case-control study (N = 350/350) indicated an association between rs2480258 and DTC risk. This ht-SNP resides within a linkage disequilibrium block spanning intron VIII and the 3'-untranslated region. Extended analysis in a large replication set (2429 controls and 767 cases) confirmed the association, with odds ratios for GA and AA genotypes of 1.24 (95 % confidence interval (CI) 1.03-1.48) and 1.56 (95 % CI, 1.06-2.30), respectively. Functionally, the minor allele was associated with low levels of CYP2E1 mRNA and protein expression as well as lower enzymatic activity in a series of 149 human liver samples. Our data support the hypothesis that inter-individual differences in CYP2E1 activity could modulate the risk of developing DTC suggesting that the exposure to specific xenobiotics, such as AA, could play a role in this process.

Synergistic effect of temperature and point defect on the mechanical properties of single layer and bi-layer graphene

NASA Astrophysics Data System (ADS)

Debroy, Sanghamitra; Pavan Kumar, V.; Vijaya Sekhar, K.; Acharyya, Swati Ghosh; Acharyya, Amit

2017-10-01

The present study reports a comprehensive molecular dynamics simulation of the effect of a) temperature (300-1073 K at intervals of every 100 K) and b) point defect on the mechanical behaviour of single (armchair and zigzag direction) and bilayer layer graphene (AA and AB stacking). Adaptive intermolecular reactive bond order (AIREBO) potential function was used to describe the many-body short-range interatomic interactions for the single layer graphene sheet. Moreover, Lennard Jones model was considered for bilayer graphene to incorporate the van der Waals interactions among the interlayers of graphene. The effect of temperature on the strain energy of single layer and bilayer graphene was studied in order to understand the difference in mechanical behaviour of the two systems. The strength of the pristine single layer graphene was found to be higher as compared to bilayer AA stacked graphene at all temperatures. It was observed at 1073 K and in the presence of vacancy defect the strength for single layer armchair sheet falls by 30% and for bilayer armchair sheet by 33% as compared to the pristine sheets at 300 K. The AB stacked graphene sheet was found to have a two-step rupture process. The strength of pristine AB sheet was found to decrease by 22% on increase of temperature from 300 K to 1073 K.

Influence of Host Interleukin-10 Polymorphisms on Development of Traveler's Diarrhea Due to Heat-Labile Enterotoxin-Producing Escherichia coli in Travelers from the United States Who Are Visiting Mexico▿

PubMed Central

Flores, Jose; DuPont, Herbert L.; Lee, Stephanie A.; Belkind-Gerson, Jaime; Paredes, Mercedes; Mohamed, Jamal A.; Armitige, Lisa Y.; Guo, Dong-Chuan; Okhuysen, Pablo C.

2008-01-01

Up to 60% of U.S. visitors to Mexico develop traveler's diarrhea (TD), mostly due to enterotoxigenic Escherichia coli (ETEC) strains that produce heat-labile (LT) and/or heat-stable (ST) enterotoxins. Distinct single-nucleotide polymorphisms (SNPs) within the interleukin-10 (IL-10) promoter have been associated with high, intermediate, or low production of IL-10. We conducted a prospective study to investigate the association of SNPs in the IL-10 promoter and the occurrence of TD in ETEC LT-exposed travelers. Sera from U.S. travelers to Mexico collected on arrival and departure were studied for ETEC LT seroconversion by using cholera toxin as the antigen. Pyrosequencing was performed to genotype IL-10 SNPs. Stools from subjects who developed diarrhea were also studied for other enteropathogens. One hundred twenty-one of 569 (21.3%) travelers seroconverted to ETEC LT, and among them 75 (62%) developed diarrhea. Symptomatic seroconversion was more commonly seen in subjects who carried a genotype producing high levels of IL-10; it was seen in 83% of subjects with the GG genotype versus 54% of subjects with the AA genotype at IL-10 gene position −1082 (P, 0.02), in 71% of those with the CC genotype versus 33% of those with the TT genotype at position −819 (P, 0.005), and in 71% of those with the CC genotype versus 38% of those with the AA genotype at position −592 (P, 0.02). Travelers with the GCC haplotype were more likely to have symptomatic seroconversion than those with the ATA haplotype (71% versus 38%; P, 0.002). Travelers genetically predisposed to produce high levels of IL-10 were more likely to experience symptomatic ETEC TD. PMID:18579697

Maternal Folate Status and the BHMT c.716G>A Polymorphism Affect the Betaine Dimethylglycine Pathway during Pregnancy.

PubMed

Colomina, Jose M; Cavallé-Busquets, Pere; Fernàndez-Roig, Sílvia; Solé-Navais, Pol; Fernandez-Ballart, Joan D; Ballesteros, Mónica; Ueland, Per M; Meyer, Klaus; Murphy, Michelle M

2016-10-09

The effect of the betaine: homocysteine methyltransferase BHMT c.716G>A (G: guanosine; A: adenosine) single nucleotide polymorphism (SNP) on the BHMT pathway is unknown during pregnancy. We hypothesised that it impairs betaine to dimethylglycine conversion and that folate status modifies its effect. We studied 612 women from the Reus Tarragona Birth Cohort from ≤12 gestational weeks (GW) throughout pregnancy. The frequency of the variant BHMT c.716A allele was 30.8% (95% confidence interval (CI): 28.3, 33.5). In participants with normal-high plasma folate status (>13.4 nmol/L), least square geometric mean [95% CI] plasma dimethylglycine (pDMG, µmol/L) was lower in the GA (2.35 [2.23, 2.47]) versus GG (2.58 [2.46, 2.70]) genotype at ≤12 GW ( p < 0.05) and in the GA (2.08 [1.97, 2.19]) and AA (1.94 [1.75, 2.16]) versus GG (2.29 [2.18, 2.40]) genotypes at 15 GW ( p < 0.05). No differences in pDMG between genotypes were observed in participants with possible folate deficiency (≤13.4 nmol/L) ( p for interactions at ≤12 GW: 0.023 and 15 GW: 0.038). PDMG was lower in participants with the AA versus GG genotype at 34 GW (2.01 [1.79, 2.25] versus 2.44 [2.16, 2.76] and at labour, 2.51 [2.39, 2.64] versus 3.00 [2.84, 3.18], ( p < 0.01)). Possible deficiency compared to normal-high folate status was associated with higher pDMG in multiple linear regression analysis (β coefficients [SEM] ranging from 0.07 [0.04], p < 0.05 to 0.20 [0.04], p < 0.001 in models from early and mid-late pregnancy) and the AA compared to GG genotype was associated with lower pDMG (β coefficients [SEM] ranging from -0.11 [0.06], p = 0.055 to -0.23 [0.06], p < 0.001). During pregnancy, the BHMT pathway is affected by folate status and by the variant BHMT c.716A allele.

The interleukin-10-1082 'A' allele and abdominal aortic aneurysms.

PubMed

Bown, Matthew J; Lloyd, Geraint M; Sandford, Rebecca M; Thompson, John R; London, Nicholas J M; Samani, Nilesh J; Sayers, Robert D

2007-10-01

Abdominal aortic aneurysms (AAA) are caused by inflammatory processes in the wall of the aorta resulting in degradation of structural proteins. This inflammatory process is mediated, in part, by cytokines, and interleukin-10 (IL-10) is a predominantly anti-inflammatory cytokine. A single nucleotide polymorphism in the promoter region of the IL-10 gene that affects transcription has been associated with AAA in a small study. The aim of this study was to determine whether this polymorphism is associated with AAA and also examine its effect on the growth of small AAA. A case control study was performed. A total of 389 patients with AAA and 404 healthy controls were recruited. IL-10-1082 polymorphisms were determined by polymerase chain reaction-based methods. In the case of patients with small AAA (<5.5 cm), serial size measurements were recorded to determine mean growth rate. There was a statistically significant difference both in allele and genotype frequencies between the case and control groups with the IL-10-1082 'A' allele being more common in the AAA group (P = .006). In the AAA group, genotype frequencies were as follows: GG 84, GA 201, and AA 104. In the control group, the genotype frequencies were GG 118, GA 205, and AA 81. The odds ratio for the 'A' allele as a risk factor for AAA was 1.50 (95% confidence interval 1.09 to 2.07). Regression modeling revealed that the IL-10-1082 genotype was, however, not independently associated with AAA if age, tobacco use, hypertension, and history of coronary or peripheral artery disease was taken into account. There was a trend towards lower plasma IL-10 level in IL-10 AA carriers, but the IL-10 'A' allele did not have any discernible effect on the growth of small AAA. This study demonstrates that the IL-10-1082 'A' allele is associated with AAA, although this association is likely to be secondary to an association between IL-10-1082 genotype and other markers of cardiovascular disease rather than AAA per se.

Association with leptin gene C.-2548 G>A polymorphism, serum leptin levels, and body mass index in Turkish obese patients.

PubMed

Sahin, Deniz Say; Tumer, Cemil; Demir, Cemil; Celik, M Murat; Celik, Mustafa; Ucar, Edip; Gunesacar, Ramazan

2013-03-01

Leptin is a protein hormone which plays a critical role in the regulation of both body-weight through reducing food intake and stimulating energy expenditure. Several polymorphisms in leptin gene (LEP), which encodes for leptin, have been described. However, its association with obesity is still controversial. Therefore, in the present study, we aimed to investigate whether LEP c.-2548 G>A polymorphism was associated with serum leptin levels, lipid parameters, and body mass index in Turkish obese patients. Forty-seven obese patients and 48 healthy individuals were included in the study. Blood samples were collected for DNA extraction. LEP c.-2548 G>A polymorphism were detected using polymerase chain reaction-restriction fragment length polymorphism technique. Serum leptin levels and lipid parameters were measured by ELISA and enzyme colorimetric assay techniques, respectively. GA or AA genotypes and A allele carrier frequencies of the c.-2548 G>A polymorphism in the LEP were higher in obese (38.3, 34.0 and 72.3 %) when compared with controls (14.6, 12.5, and 27.1 %; p = 0.011, 0.016, and 0.002, respectively). On the other hand, AA or AG genotypes were also related to increased serum leptin levels (p < 0.001) and body mass index (p < 0.0001). All these consequences showed that LEP -2548 AA or AG genotypes are important predictors for increased levels of leptin and BMI in Turkish obese patients and it may be a useful marker for obesity risk in our population.

Association of Methylenetetrahydrofolate Reductase C677T and A1298C Gene Polymorphisms With Recurrent Pregnancy Loss in Syrian Women.

PubMed

Al-Achkar, Walid; Wafa, Abdulsamad; Ammar, Samer; Moassass, Faten; Jarjour, Rami A

2017-09-01

C677T polymorphism of the methylenetetrahydrofolate reductase ( MTHFR) gene was a risk factor for recurrent pregnancy loss (RPL), but few studies have confirmed a possible role of MTHFR A1298C polymorphism in RPL risk. This study was carried out to determine the influence of the MTHFR gene polymorphisms in RPL Syrian women. A case-control study was performed on 2 groups (106 healthy and 100 RPL women). The frequency of the MTHFR gene polymorphisms was determined by polymerase chain reaction based on restriction fragment length gene polymorphism. In the RPL group, the genotype frequencies of MTHFR C677T were CC (41%), CT (41%), and TT (18%), and in the control group, the frequencies were CC (62.2%), CT (36.7%), and TT (1%). Statistical analysis showed a homozygous TT genotype and T allele were significantly different in the RPL group ( P = .000003 and P = .000019, respectively). The genotype frequencies of MTHFR A1298C were AA (53%), AC (44%), and CC (8%) in the RPL group, whereas in the control group, these were AA (61.3%), AC (37.8%), and CC (1%). A significant difference in the CC genotype and C allelic frequencies in the RPL women was observed ( P = .014 and P = .064, respectively). The patients having compound heterozygous (677 CT/1298AC) were associated with an estimated 4.86-fold increase in risk of pregnancy loss compared to individuals with a wild type ( P = .012). Our findings indicate that RPL women with homozygous genotype for (C677T and A1298C) either alone or compound heterozygous genotypes have a high risk of pregnancy loss in Syrian women.

Association of ACE and FACTOR VII gene variability with the risk of coronary heart disease in north Indian population.

PubMed

Sobti, R C; Maithil, Nishi; Thakur, Hitender; Sharma, Yashpaul; Talwar, K K

2010-08-01

The angiotensin converting enzyme (ACE) is a key factor in the production of angiotensin II and in the degradation of bradykinin. Chronic exposure to high levels of circulating and tissue ACE predispose to vascular wall thickening and atherosclerosis. Factor VII (FACTOR VII) is the first enzyme in the extrinsic pathway of the blood coagulation system and plays a key role in hemostasis; it also contributes to the occurrence of thrombotic events. In this study, we have examined the association of ACE and FACTOR VII gene in coronary heart disease patients (n = 300) and their age-matched controls (n = 300). Genotyping was done by PCR-RFLP method. No significant difference was observed in the distribution of I/D genotypes of ACE between cases and controls. In case of FACTOR VII R353Q polymorphism, there was not much difference in the distribution of alleles. AA genotype had protective effect for CHD (OR 0.56, 95% CI 0.37-0.83, P = 0.001). In case of FACTOR VII VNTR, there was difference in the distribution of alleles, H6 (73.5) and H7 (25.5) in cases, and H6 (70.5) and H7 (30.5) in controls. H6H7 and H7H7 genotypes had a protective effect for CHD with OR 0.27, 95% CI 0.18-0.41, P < 0.001, and OR 0.18, 95% CI 0.09-0.36, P < 0.001. Our study showed D allele of ACE to be associated with marginal risk of CHD, AA genotype of FACTOR VII R353Q and H6H7 and H7H7 genotypes of FACTOR VII VNTR showed protective effect for CHD.

Association between angiotensin II type 1 receptor gene polymorphism and essential hypertension: the Ohasama Study.

PubMed

Sugimoto, Ken; Katsuya, Tomohiro; Ohkubo, Takayoshi; Hozawa, Atsushi; Yamamoto, Koichi; Matsuo, Akiko; Rakugi, Hiromi; Tsuji, Ichiro; Imai, Yutaka; Ogihara, Toshio

2004-08-01

Gene targeting approaches have suggested that the angiotensin II type 1 receptor (AT1R) is involved in blood pressure (BP) regulation and modulation of the effect of angiotensin II. The A1166C polymorphism of the AT1 receptor gene (AT1R/A1166C) is associated with hypertension in Caucasians, but not in Japanese. The goal of this study, the Ohasama Study, was to examine the association between AT1R/A1166C and hypertension, especially home BP, in the Japanese general population. The Ohasama Study was a cohort study based on Japanese rural residents of Ohasama Town in the northern part of Japan. Subjects who gave informed consent to the study protocol and genetic analysis were recruited. Home BP was measured twice in the morning within 1 h of waking up and in the evening just before going to bed. The TaqMan polimerase chain reaction (PCR) method clearly determined AT1R/A1166C genotypes (n =1,207). The genotype distribution of AT1R/A1166C was as follows: AA 84%; AC 15%; CC 1%. There was almost no difference in baseline characteristics among the AT1R genotypes (AA, AC, CC). In the subjects not receiving antihypertensive medication (n =817), both casual BP and home BP were not different among the AT1R genotypes after adjusting for confounding factors (age, sex, body mass index, current smoking habit and current alcohol consumption). The frequency of hypertension showed no difference among AT1R genotypes after adjusting for confounding factors, though the AC and CC genotypes were more frequent in hypertensives than in normotensives. Our data suggested that the AT1R/A1166C polymorphism is not a major genetic predisposing factor for hypertension in Japanese.

MMP3 and TIMP2 gene variants as predisposing factors for Achilles tendon pathologies: Attempted replication study in a British case-control cohort.

PubMed

El Khoury, Louis; Ribbans, William J; Raleigh, Stuart M

2016-09-01

Variants within the MMP3 (rs679620) and TIMP2 (rs4789932) genes have been associated with the risk of Achilles tendon pathology (ATP) in populations from South Africa and Australia. This study aimed to determine whether these variants were associated with the risk of ATP in British Caucasians. We recruited 118 cases with ATP, including a subset of 25 individuals with Achilles tendon rupture (RUP) and 131 controls. DNA samples were isolated from saliva and genotyped using qPCR. For the TIMP2 rs4789932 variant we found a significant (p = 0.038) difference in the genotype distribution frequency between males with ATP (CC, 39.4%; CT, 43.7%; TT, 16.9%) compared to male controls (CC, 20.7%; CT, 59.8%; TT, 19.5%). We also observed a difference in the TIMP2 rs4789932 genotype distribution between males with rupture compared to male controls (p = 0.038). The MMP3 rs679620 GG genotype was found to be overrepresented in the Achilles tendon rupture (RUP) group (AA, 24.0%; AG, 32.0%; GG, 44.0%) compared to controls (AA, 26.7%; AG, 54.2%; GG, 19.1%). In conclusion, the CT genotype of the TIMP2 rs4789932 variant was associated with lower risk of ATP in males. Furthermore, while we revealed differences for both variants in genotype distribution between the RUP and control groups, the sample size of the RUP group was small and confirmation would be required in additional cohorts. Finally, although both the TIMP2 rs4789932 and MMP3 rs679620 variants tentatively associated with ATP, there were differences in the direction of association compared to earlier work.

UCHL1 S18Y variant is a risk factor for Parkinson’s disease in Japan

PubMed Central

2012-01-01

Background A recent meta-analysis on the UCHL1 S18Y variant and Parkinson’s disease (PD) showed a significant inverse association between the Y allele and PD; the individual studies included in that meta-analysis, however, have produced conflicting results. We examined the relationship between UCHL1 S18Y single nucleotide polymorphism (SNP) and sporadic PD in Japan. Methods Included were 229 cases within 6 years of onset of PD, defined according to the UK PD Society Brain Bank clinical diagnostic criteria. Controls were 357 inpatients and outpatients without neurodegenerative disease. Adjustment was made for sex, age, region of residence, smoking, and caffeine intake. Results Compared with subjects with the CC or CA genotype of UCHL1 S18Y SNP, those with the AA genotype had a significantly increased risk of sporadic PD: the adjusted OR was 1.57 (95 % CI: 1.06 − 2.31). Compared with subjects with the CC or CA genotype of UCHL1 S18Y and the CC or CT genotype of SNCA SNP rs356220, those with the AA genotype of UCHL1 S18Y and the TT genotype of SNP rs356220 had a significantly increased risk of sporadic PD; the interaction, however, was not significant. Our previous investigation found significant inverse relationships between smoking and caffeine intake and PD in this population. There were no significant interactions between UCHL1 S18Y and smoking or caffeine intake affecting sporadic PD. Conclusions This study reveals that the UCHL1 S18Y variant is a risk factor for sporadic PD. We could not find evidence for interactions affecting sporadic PD between UCHL1 S18Y and SNCA SNP rs356220, smoking, or caffeine intake. PMID:22839974

Association of IL-13 gene polymorphisms with airway hyperresponsiveness in a Japanese adult asthmatic population.

PubMed

Utsumi, Yu; Sasaki, Nobuhito; Nagashima, Hiromi; Suzuki, Naomi; Nakamura, Yutaka; Yamashita, Masahiro; Kobayashi, Hitoshi; Yamauchi, Kohei

2013-09-01

A single nucleotide polymorphism (SNP; rs20541) in the IL-13 gene has been recognized as a risk factor for asthma. This SNP causes Arg to Gln (Q) substitution at position 110 in the mature IL-13 protein. We have recently showed that FEV1 in asthmatics with the Q110 variant of IL-13 declined faster, and progressive airway remodeling was observed in these subjects (Wynn, 2003 [1]). However, the effects of the IL-13 variant on airway hyperresponsiveness (AHR) remain to be elucidated. We analyzed the relationship between SNP rs20541 in IL-13 and AHR in asthmatics. We recruited 182 asthmatics who visited the asthma outpatient clinic at Iwate Medical University Hospital from 2006 to 2011. Subjects were genotyped for rs20541. Asthma severity, atopic status, age of asthma onset, serum IgE concentration, AHR, and pulmonary function were studied in these subjects. AHR was measured using the continuous methacholine inhalation method (Astograph; Chest; Tokyo, Japan). Genotyping of rs20541 revealed 26 A/A, 77 A/G, and 79 G/G patient genotypes. The D min (U) of the 3 genotypes was 1.17±0.300 in A/A, 1.99±0.35 in A/G, and 2.85±0.39 in G/G. The D min in the 3 genotypes was significantly different. Spirometric data revealed that % FEV1 and % FEF75 were significantly different among the 3 groups of IL-13 genotypes, whereas no significant differences were observed in therapeutic steps, atopic status, house dust mite sensitization, or serum IgE concentration. The SNP rs20541 in IL-13 was associated with AHR in Japanese adult asthmatics. Copyright © 2013 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

[Genetic polymorphisms of ARL15 and HLA-DMA are associated with rheumatoid arthritis in Han population from northwest China].

PubMed

Wang, Jiao; Qi, Xiaoming; Zhang, Xiaozhen; Yan, Wen; You, Chongge

2017-12-01

Objective To establish the methods for detecting single nucleotide polymorphisms (SNPs) of ADP-ribosylation factor-like GTPase 15 (ARL15), major histocompatibility complex class II-DM alpha (HLA-DMA ) and nuclear factor kappa B subunit 2 (NFKB2) genes using high resolution melting (HRM) technology, and to explore the association of those SNPs with the susceptibility of rheumatoid arthritis (RA) in northwestern Han Chinese population. Methods The PCR-HRM detection system for four SNPs (rs255758, rs1063478, rs397514331 and rs397514332) was established for genotyping, and gene sequencing was performed to validate the genotyping ability of the system. 588 RA cases and 200 controls were enrolled in a case-control study to analyze the associations of ARL15 and HLA-DMA gene polymorphisms with RA risk. Results The direct sequencing validated that the established PCR-HRM detection system could be used for genotyping clinical samples correctly. The mutated genotype of rs397514331 and rs397514332 from NFKB2 gene are not found in this study. The genotype frequencies of rs255758 and rs1063478 had statistical difference between the cases and controls, but no statistical difference in allelic frequencies. Under the dominant model (AA vs AC/CC), the AA genotype of rs255758 decreases the RA risk (OR=0.666, 95%CI=0.478-0.927, P=0.016). Conclusion The method of PCR-HRM we established can be applied to the routine detection of rs255758, rs1063478, rs397514331 and rs397514332. The ARL15 and HLA-DMA gene polymorphisms are associated with RA risk in Northwestern Han Chinese population.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tokovinin, Andrei, E-mail: atokovinin@ctio.noao.edu

Seven spectroscopic orbits in nearby solar-type multiple stars are presented. The primary of the chromospherically active star HIP 9642 is a 4.8 day double-lined pair; the outer 420 year visual orbit is updated, but remains poorly constrained. HIP 12780 is a quadruple system consisting of the resolved 6.7 year pair FIN 379 Aa,Ab, for which the combined orbit, masses, and orbital parallax are determined here, and the single-lined binary Ba,Bb with a period of 27.8 days. HIP 28790 is a young quintuple system composed of two close binaries, Aa,Ab and Ba,Bb, with periods of 221 and 13 days, respectively, and a singlemore » distant component C. Its subsystem Ba,Bb is peculiar, having a spectroscopic mass ratio of 0.89 but a magnitude difference of ∼2.2 mag. HIP 64478 also contains five stars: the A-component is a 29 year visual pair with a previously known 4 day twin subsystem, while the B-component is a contact binary with a period of 5.8 hr, seen nearly pole-on.« less

Determination of the full-genome sequence of hepatitis E virus (HEV) SAAS-FX17 and use as a reference to identify putative HEV genotype 4 virulence determinants.

PubMed

Zhu, Yumin; Yu, Xiaoming; Huang, Fenfen; Yu, Ruisong; Dong, Shijuan; Si, Fusheng; Zhang, Yuanshu; Li, Zhen

2012-11-08

Four major genotypes of hepatitis E virus (HEV), the causative agent of hepatitis E, have so far been recognized. While genotypes 3 and 4 are both zoonotic, the disease symptoms caused by the latter tend to be more severe. To examine if specific nucleotide/amino acid variations between genotypes 3 and 4 play a role in determining the severity of hepatitis E disease, the complete genome of one swine HEV genotype 4 isolate, SAAS-FX17, was determined and compared with other genotype 4 and genotype 3 genomes to identify putative HEV genotype 4 virulence determinants. A total of 42 conformable nt/aa variations between genotype 3 and 4 HEVs were detected, of which 19 were proposed to be potential disease severity determinants for genotype 4 strains. One potential determinant was located in each of the 5'-UTR and 3'-UTR, 3 and 12 within ORF1 and ORF2 respectively, and 2 in the junction region.

Phenome-Wide Association Study (PheWAS) for Detection of Pleiotropy within the Population Architecture using Genomics and Epidemiology (PAGE) Network

PubMed Central

Pendergrass, Sarah A.; Brown-Gentry, Kristin; Dudek, Scott; Frase, Alex; Torstenson, Eric S.; Goodloe, Robert; Ambite, Jose Luis; Avery, Christy L.; Buyske, Steve; Bůžková, Petra; Deelman, Ewa; Fesinmeyer, Megan D.; Haiman, Christopher A.; Heiss, Gerardo; Hindorff, Lucia A.; Hsu, Chu-Nan; Jackson, Rebecca D.; Kooperberg, Charles; Le Marchand, Loic; Lin, Yi; Matise, Tara C.; Monroe, Kristine R.; Moreland, Larry; Park, Sungshim L.; Reiner, Alex; Wallace, Robert; Wilkens, Lynn R.; Crawford, Dana C.; Ritchie, Marylyn D.

2013-01-01

Using a phenome-wide association study (PheWAS) approach, we comprehensively tested genetic variants for association with phenotypes available for 70,061 study participants in the Population Architecture using Genomics and Epidemiology (PAGE) network. Our aim was to better characterize the genetic architecture of complex traits and identify novel pleiotropic relationships. This PheWAS drew on five population-based studies representing four major racial/ethnic groups (European Americans (EA), African Americans (AA), Hispanics/Mexican-Americans, and Asian/Pacific Islanders) in PAGE, each site with measurements for multiple traits, associated laboratory measures, and intermediate biomarkers. A total of 83 single nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) were genotyped across two or more PAGE study sites. Comprehensive tests of association, stratified by race/ethnicity, were performed, encompassing 4,706 phenotypes mapped to 105 phenotype-classes, and association results were compared across study sites. A total of 111 PheWAS results had significant associations for two or more PAGE study sites with consistent direction of effect with a significance threshold of p<0.01 for the same racial/ethnic group, SNP, and phenotype-class. Among results identified for SNPs previously associated with phenotypes such as lipid traits, type 2 diabetes, and body mass index, 52 replicated previously published genotype–phenotype associations, 26 represented phenotypes closely related to previously known genotype–phenotype associations, and 33 represented potentially novel genotype–phenotype associations with pleiotropic effects. The majority of the potentially novel results were for single PheWAS phenotype-classes, for example, for CDKN2A/B rs1333049 (previously associated with type 2 diabetes in EA) a PheWAS association was identified for hemoglobin levels in AA. Of note, however, GALNT2 rs2144300 (previously associated with high-density lipoprotein cholesterol levels in EA) had multiple potentially novel PheWAS associations, with hypertension related phenotypes in AA and with serum calcium levels and coronary artery disease phenotypes in EA. PheWAS identifies associations for hypothesis generation and exploration of the genetic architecture of complex traits. PMID:23382687

VizieR Online Data Catalog: Solar neighborhood. XXXVII. RVs for M dwarfs (Benedict+, 2016)

NASA Astrophysics Data System (ADS)

Benedict, G. F.; Henry, T. J.; Franz, O. G.; McArthur, B. E.; Wasserman, L. H.; Jao, W.-C.; Cargile, P. A.; Dieterich, S. B.; Bradley, A. J.; Nelan, E. P.; Whipple, A. L.

2017-05-01

During this project we observed with two Fine Guidance Sensor (FGS) units: FGS 3 from 1992 to 2000, and FGS 1r from 2000 to 2009. FGS 1r replaced the original FGS 1 during Hubble Space Telescope (HST) Servicing Mission 3A in late 1999. We included visual, photographic, and CCD observations of separations and position angles from Geyer et al. 1988AJ.....95.1841G for our analysis of GJ 65 AB. We include a single observation of G 193-027 AB from Beuzit et al. 2004A&A...425..997B, who used the Adaptive Optics Bonnette system on the Canada-France-Hawaii Telescope (CFHT). For GJ 65 AB we include five Very Large Telescope/NAos-COnica (VLT/NACO) measures of position angle and separation (Kervella et al. 2016A&A...593A.127K). For our analysis of GJ 623 AB, we included astrometric observations (Martinache et al. 2007ApJ...661..496M) performed with the Palomar High Angular Resolution Observer (PHARO) instrument on the Palomar 200in (5m) telescope and with the Near InfraRed Camera 2 (NIRC2) instrument on the Keck II telescope. Separations have typical errors of 2mas. Position angle errors average 0.5°. Measurements are included for GJ 22 AC from McCarthy et al. 1991AJ....101..214M and for GJ 473 AB from Henry et al. 1992AJ....103.1369H and Torres et al. 1999AJ....117..562T, who used a two-dimensional infrared speckle camera containing a 58*62 pixel InSb array on the Steward Observatory 90in telescope. We also include infrared speckle observations by Woitas et al. 2003A&A...406..293W, who obtained fourteen separation and position angle measurements for GJ 22 AC with the near-infrared cameras MAGIC and OMEGA Cass at the 3.5m telescope on Calar Alto. We also include a few speckle observations at optical wavelengths from the Special Astrophysical Observatory 6m Bolshoi Azimuth Telescope (BTA) and 1m Zeiss (Balega et al. 1994, Cat. J/A+AS/105/503), from the CFHT (Blazit et al. 1987) and from the Differential Speckle Survey Instrument (DSSI) on the Wisconsin, Indiana, Yale, National optical astronomy observatory (WIYN) 3.5m (Horch et al. 2012, Cat. J/AJ/143/10). Where available, we use astrometric observations from HST instruments other than the FGSs, including the Faint Object Camera (FOC; Barbieri et al. 1996A&A...315..418B), the Faint Object Spectrograph (FOS; Schultz et al. 1998PASP..110...31S), the Near-Infrared Camera and Multi-Object Spectrometer (NICMOS; Golimowski et al. 2004AJ....128.1733G), and the Wide-Field Planetary Camera 2 (WFPC2; Schroeder et al. 2000AJ....119..906S; Dieterich et al. 2012, Cat. J/AJ/144/64). Our radial velocity measurements, listed in table3, are from two sources. We obtained most radial velocity data with the McDonald 2.1m Struve telescope and the Sandiford Cassegrain Echelle spectrograph, hereafter CE. The CE delivers a dispersion equivalent to 2.5km/s/pix (R=λ/Δλ=60000) with a wavelength range of 5500{<=}λ{<=}6700Å spread across 26 orders (apertures). The McDonald data were collected during 33 observing runs from 1995 to 2009. Some GJ 623 AB velocities came from the Hobby-Eberly Telescope (HET) using the Tull Spectrograph. (3 data files).

Changes of seed weight, fatty acid composition, oil and protein contents from different peanut FAD2 genotypes at different seed developmental and maturation stages

USDA-ARS?s Scientific Manuscript database

The level of oleic acid in peanut seed is one of the most important factors in determining seed quality and is controlled by two pairs of homeologous genes Fatty Acid Desaturase 2A and 2B (FAD2A and FAD2B). The genotypes of eight F8 breeding lines were determined as AABB, aaBB, AAbb, and aabb by rea...

Cytokine gene polymorphisms in Italian preterm infants: association between interleukin-10 -1082 G/A polymorphism and respiratory distress syndrome.

PubMed

Capasso, Mario; Avvisati, Rosa Anna; Piscopo, Carmelo; Laforgia, Nicola; Raimondi, Francesco; de Angelis, Filomena; Iolascon, Achille

2007-03-01

In this study, we determined the genotype frequencies of polymorphisms of cytokine genes and investigated their association with the risk of respiratory distress syndrome (RDS) in preterm infants. Genetic polymorphisms in the cytokines interleukin (IL)-10, IL-8, and tumor necrosis factor (TNF) alpha, were studied in 342 white Italian newborns (112 without RDS, 66 prematurely born with RDS, and 164 infants born at term who were included as healthy controls). The polymorphisms were analyzed by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP). The IL-10 mRNA levels were analyzed according to genotype by quantitative real-time PCR (QRT-PCR) in Epstein-Barr virus-transformed lymphoblastoid cell lines (EBV-LCLs) of 42 full-term healthy infants. Logistic regression analysis demonstrated the risk of RDS to be significantly lower in preterm infants with an IL-10 -1082 GG/GA genotype than in those with an AA genotype [odds ratio (OR) = 0.48, 95% confidence interval (CI): 0.24-0.95, p = 0.03]. QRT-PCR analyses showed that the IL-10 mRNA levels were significantly higher in 27 IL-10 -1082 GG/GA carriers compared with 15 IL-10 -1082 AA carriers (p = 0.03). We conclude that the IL-10 -1082 GG/GA polymorphism may have a role in RDS development in premature infants.

Association between XRCC1 polymorphisms and laryngeal cancer susceptibility in a Chinese sample population.

PubMed

Wu, W Q; Zhang, L S; Liao, S P; Lin, X L; Zeng, J; Du, D

2016-10-05

Laryngeal cancer is the major malignant tumor affecting the upper respiratory tract. Previous studies have reported on the association between XRCC1 genetic polymorphisms and risk of laryngeal cancer, but with conflicting results. In this study, we attempted to assess the association between XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphisms and risk of laryngeal cancer in a Chinese population. A total of 126 laryngeal cancer patients and 254 control subjects were recruited to this study from the Second Medical College of Jinan University between December 2013 and May 2015. The XRCC1 Arg194Trp, Arg280His, and Arg399Gln polymorphic sites were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Our results revealed a significant association between the AA genotype of XRCC1 Arg280His [odds ratio (OR) = 2.51, 95% confidence interval (CI) = 1.29-4.87, P = 0.01] and an increased risk of laryngeal cancer susceptibility compared to the GG genotype. Moreover, the A allele showed a higher risk of laryngeal cancer susceptibility compared to the G allele (OR = 1.63, 95%CI = 1.19-2.50, P = 0.002). In conclusion, the results of our study suggest that the AA genotype and A allele of the XRCC1 Arg280His polymorphism are associated with an increased laryngeal cancer risk in a Chinese population.

Relationship between Fas and Fas Ligand gene polymorphisms and pre-eclampsia.

PubMed

Masoumi, Elham; Tavakkol-Afshari, Jalil; Nikpoor, Amin Reza; Ghaffari-Nazari, Haniyeh; Tahaghoghi-Hajghorbani, Sahar; Jalali, Seyed Amir

2016-10-01

In normal pregnancy, the Th1 subtype, responsible for the production of inflammatory cytokines, is reduced, and the Th2 subtype is increased to prohibit inflammation. In pre-eclampsia, the Th1 cell population is increased; thus, subsequent inflammation and trophoblast destruction occur. Polymorphisms in the Fas and Fas Ligand (FasL) promoter regions can influence Fas and FasL expression and accused to increase of Th1 subtype. DNA samples from 153 pregnant women with pre-eclampsia and 140 controls were genotyped through polymerase chain reaction-restriction fragment length polymorphism. A Fisher's exact test was used to compare the distribution of individual polymorphisms. Fas-1377 AA, AG and GG genotypes were observed in 2.61%, 18.30% and 79.08% in the pre-eclampsia group opposed to 0%, 27.14% and 72.85% in the control group (P = 0.037), respectively. Fas-670 AA, AG and GG genotypes were observed in 37.9%, 41.8% and 20.3% of pre-eclampsia patients compared with 33.6%, 50.7% and 15.7% in healthy pregnant women (P = 0.291), respectively. No statically significant differences in the FasL-844 genotype were observed between the groups (P = 0.69). The Fas-1377G > A polymorphism is associated with a higher risk of pre-eclampsia. © 2016 Japan Society of Obstetrics and Gynecology.

Diagnostic potential of monoclonal antibodies developed against C-terminal polypeptide of P. falciparum Histidine Rich Protein2 (PfHRP2) in malaria infected patients from India.

PubMed

Verma, Reena; Chandy, Sara; Jayaprakash, N S; Manoharan, Anand; Vijayalakshmi, M A; Venkataraman, Krishnan

2017-09-01

Malaria, caused by Plasmodium falciparum has become a major health burden in most tropical and developing countries. P. falciparum Histidine Rich Protein2 (PfHRP2), which exhibits polymorphism, is being widely used as a diagnostic marker. Recently, we reported the development of monoclonal antibodies against conserved C-terminal 105 amino acids of PfHRP2 for malaria diagnosis. Now, in this study, the diagnostic performance of two anti-C-terminal PfHRP2 mAbs (b10c1 and Aa3c10) were evaluated with 100 blood samples from clinically identified malaria patients from seven different geographical centers in India. Sandwich ELISA, polymerase chain reaction (PCR) and statistical tools were used for the evaluation of the performance of the anti-C-terminal PfHRP2 mAb. These mAbs detected P. falciparum (mean OD value 1.525 ± 0.56) malaria with great accuracy with no cross reactivity with P. Plasmodium vivax (mean OD value 0.285 ± 0.051) and normal healthy control samples (mean OD value 0.185 ± 0.06) in Sandwich ELISA assay. The samples which were RDT negative for P. falciparum were also reactive in Sandwich ELISA with mean OD value of (1.303 ± 0.532). The amount of PfHRP2 antigen in the patients' blood sample was quantified and categorized into three distinct groups having the HRP2 antigen in high, intermediate and low amounts. The presence of Pfhrp2 gene was also confirmed by PCR analysis. The sensitivity and specificity of the mAb were found to be 95 and 96% respectively. These data strongly suggest that the anti-C-terminal PfHRP2 mAbs b10c1 and Aa3c10 have merits for improvising the existing malarial diagnostics.

Association of eNOS and ACE gene polymorphisms and plasma nitric oxide with risk of non-small cell lung cancer in South India.

PubMed

Peddireddy, Vidyullatha; Badabagni, Siva Prasad; Gundimeda, Sandhya Devi; Mundluru, Hema Prasad

2018-01-01

The role of ACE and eNOS gene polymorphisms and their association with various cancers were reported. However, their role in the lung cancer is unclear. In this study, we analyzed eNOS and ACE gene polymorphisms and the risk of non-small cell lung cancer (NSCLC) in South Indian population. For the eNOS gene, the homozygous "AA" genotypic frequency was significantly associated with NSCLC with an overall risk of 3.6-fold (P = 0.006, odds ratio = 3.58, 95% confidence interval = 1.66, 7.723). The heterozygous "I/D" genotypic frequency of ACE gene was significantly higher in NSCLC patients when compared to the controls with a 2.29-fold risk for NSCLC. Multiple regression analyses indicated that gender, smoking status, and polymorphisms in eNOS and ACE genes as the strongest predicting factors for an increased susceptibility to NSCLC. We report for the first time that polymorphisms in the eNOS "A/A" (homozygous mutant) and ACE "I/D" genotypes might contribute to the increased risk of NSCLC in the South Indian population. © 2016 John Wiley & Sons Ltd.

Low-density lipoprotein receptor genetic polymorphism in chronic hepatitis C virus Egyptian patients affects treatment response

PubMed Central

Naga, Mazen; Amin, Mona; Algendy, Dina; Elbadry, Ahmed; Fawzi, May; Foda, Ayman; Esmat, Serag; Sabry, Dina; Rashed, Laila; Gabal, Samia; Kamal, Manal

2015-01-01

AIM: To correlate a genetic polymorphism of the low-density lipoprotein (LDL) receptor with antiviral responses in Egyptian chronic hepatitis C virus (HCV) patients. METHODS: Our study included 657 HCV-infected patients with genotype 4 who received interferon-based combination therapy. Patients were divided into two groups based on their response to therapy: 356 were responders, and 301 were non-responders. Patients were compared to 160 healthy controls. All patients and controls underwent a thorough physical examination, measurement of body mass index (BMI) and the following laboratory tests: serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, albumin, total bilirubin, direct bilirubin, prothrombin time, prothrombin concentration, INR, complete blood count, serum creatinine, fasting blood sugar, HCV antibody, and hepatitis B surface antigen. All HCV patients were further subjected to the following laboratory tests: HCV-RNA using quantitative polymerase chain reaction (PCR), antinuclear antibodies, thyroid-stimulating hormone, an LDL receptor (LDLR) genotype study of LDLR exon8c.1171G>A and exon10c.1413G>A using real-time PCR-based assays, abdominal ultrasonography, ultrasonographic-guided liver biopsy, and histopathological examination of liver biopsies. Correlations of LDL receptor polymorphisms with HAI, METAVIR score, presence of steatosis, and BMI were performed in all cases. RESULTS: There were no statistically significant differences in response rates between the different types of interferon used or LDLR exon10c.1413G>A. However, there was a significant difference in the frequency of the LDL receptor exon8c.1171G>A genotype between cases (AA: 25.9%, GA: 22.2%, GG: 51.9%) and controls (AA: 3.8%, GA: 53.1% and GG: 43.1%) (P < 0.001). There was a statistically significant difference in the frequency of the LDLR exon 8C:1171 G>A polymorphism between responders (AA: 3.6%, GA: 15.2%, GG: 81.2%) and non-responders (AA: 52.2%, GA: 30.6%, GG: 17.2%) (P < 0.001). The G allele of LDL receptor exon8c.1171G>A predominated in cases and controls over the A allele, and a statistically significant association with response to interferon was observed. The frequency of the LDLR exon8c.1171G>A allele in non-responders was: A: 67.4% and G: 32.6 vs A: 11.2% and G: 88.8% in responders (P < 0.001). Therefore, carriers of the A allele exhibited a 16.4 times greater risk for non-response. There was a significant association between LDL receptors exon8 c.1171G>A and HAI (P < 0.011). There was a significant association between LDL receptors exon8c.1171G>A and BMI. The mean BMI level was highest in patients carrying the AA genotype (28.7 ± 4.7 kg/m2) followed by the GA genotype (28.1 ± 4.8 kg/m2). The lowest BMI was the GG genotype (26.6 ± 4.3 kg/m2) (P < 0.001). The only significant associations were found between LDL receptors exon8 c.1171G>A and METAVIR score or steatosis (P < 0.001). CONCLUSION: LDL receptor gene polymorphisms play a role in the treatment response of HCV and the modulation of disease progression in Egyptians infected with chronic HCV. PMID:26494968

Low-density lipoprotein receptor genetic polymorphism in chronic hepatitis C virus Egyptian patients affects treatment response.

PubMed

Naga, Mazen; Amin, Mona; Algendy, Dina; Elbadry, Ahmed; Fawzi, May; Foda, Ayman; Esmat, Serag; Sabry, Dina; Rashed, Laila; Gabal, Samia; Kamal, Manal

2015-10-21

To correlate a genetic polymorphism of the low-density lipoprotein (LDL) receptor with antiviral responses in Egyptian chronic hepatitis C virus (HCV) patients. Our study included 657 HCV-infected patients with genotype 4 who received interferon-based combination therapy. Patients were divided into two groups based on their response to therapy: 356 were responders, and 301 were non-responders. Patients were compared to 160 healthy controls. All patients and controls underwent a thorough physical examination, measurement of body mass index (BMI) and the following laboratory tests: serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, albumin, total bilirubin, direct bilirubin, prothrombin time, prothrombin concentration, INR, complete blood count, serum creatinine, fasting blood sugar, HCV antibody, and hepatitis B surface antigen. All HCV patients were further subjected to the following laboratory tests: HCV-RNA using quantitative polymerase chain reaction (PCR), antinuclear antibodies, thyroid-stimulating hormone, an LDL receptor (LDLR) genotype study of LDLR exon8c.1171G>A and exon10c.1413G>A using real-time PCR-based assays, abdominal ultrasonography, ultrasonographic-guided liver biopsy, and histopathological examination of liver biopsies. Correlations of LDL receptor polymorphisms with HAI, METAVIR score, presence of steatosis, and BMI were performed in all cases. There were no statistically significant differences in response rates between the different types of interferon used or LDLR exon10c.1413G>A. However, there was a significant difference in the frequency of the LDL receptor exon8c.1171G>A genotype between cases (AA: 25.9%, GA: 22.2%, GG: 51.9%) and controls (AA: 3.8%, GA: 53.1% and GG: 43.1%) (P < 0.001). There was a statistically significant difference in the frequency of the LDLR exon 8C:1171 G>A polymorphism between responders (AA: 3.6%, GA: 15.2%, GG: 81.2%) and non-responders (AA: 52.2%, GA: 30.6%, GG: 17.2%) (P < 0.001). The G allele of LDL receptor exon8c.1171G>A predominated in cases and controls over the A allele, and a statistically significant association with response to interferon was observed. The frequency of the LDLR exon8c.1171G>A allele in non-responders was: A: 67.4% and G: 32.6 vs A: 11.2% and G: 88.8% in responders (P < 0.001). Therefore, carriers of the A allele exhibited a 16.4 times greater risk for non-response. There was a significant association between LDL receptors exon8 c.1171G>A and HAI (P < 0.011). There was a significant association between LDL receptors exon8c.1171G>A and BMI. The mean BMI level was highest in patients carrying the AA genotype (28.7 ± 4.7 kg/m(2)) followed by the GA genotype (28.1 ± 4.8 kg/m(2)). The lowest BMI was the GG genotype (26.6 ± 4.3 kg/m(2)) (P < 0.001). The only significant associations were found between LDL receptors exon8 c.1171G>A and METAVIR score or steatosis (P < 0.001). LDL receptor gene polymorphisms play a role in the treatment response of HCV and the modulation of disease progression in Egyptians infected with chronic HCV.

Antigenic characterisation of yeast-expressed lyssavirus nucleoproteins.

PubMed

Kucinskaite, Indre; Juozapaitis, Mindaugas; Serva, Andrius; Zvirbliene, Aurelija; Johnson, Nicholas; Staniulis, Juozas; Fooks, Anthony R; Müller, Thomas; Sasnauskas, Kestutis; Ulrich, Rainer G

2007-12-01

In Europe, three genotypes of the genus Lyssavirus, family Rhabdoviridae, are present, classical rabies virus (RABV, genotype 1), European bat lyssavirus type 1 (EBLV-1, genotype 5) and European bat lyssavirus type 2 (EBLV-2, genotype 6). The entire authentic nucleoprotein (N protein) encoding sequences of RABV (challenge virus standard, CVS, strain), EBLV-1 and EBLV-2 were expressed in yeast Saccharomyces cerevisiae at high level. Purification of recombinant N proteins by caesium chloride gradient centrifugation resulted in yields between 14-17, 25-29 and 18-20 mg/l of induced yeast culture for RABV-CVS, EBLV-1 and EBLV-2, respectively. The purified N proteins were evaluated by negative staining electron microscopy, which revealed the formation of nucleocapsid-like structures. The antigenic conformation of the N proteins was investigated for their reactivity with monoclonal antibodies (mAbs) directed against different lyssaviruses. The reactivity pattern of each mAb was virtually identical between immunofluorescence assay with virus-infected cells, and ELISA and dot blot assay using the corresponding recombinant N proteins. These observations lead us to conclude that yeast-expressed lyssavirus N proteins share antigenic properties with naturally expressed virus protein. These recombinant proteins have the potential for use as components of serological assays for lyssaviruses.

[Comparative studies of serological typing and HLA-A, B antigen genotyping with PCR using sequence-specific primers].

PubMed

Wu, Da-lin; Ling, Han-xin; Tang, Hao

2004-11-01

To evaluate the accuracy of PCR with sequence-specific primers (PCR-SSP) for HLA-I genotyping and analyze the causes of the errors occurring in the genotyping. DNA samples and were obtained from 34 clinical patients, and serological typing with monoclonal antibody (mAb) and HLA-A and, B antigen genotyping with PCR-SSP were performed. HLA-A and, B alleles were successfully typed in 34 clinical samples by mAb and PCR-SSP. No false positive or false negative results were found, and the erroneous and missed diagnosis rates were obviously higher in serological detection, being 23.5% for HLA-A and 26.5% for HLA-B. Error or confusion was more likely to occur in the antigens of A2 and A68, A32 and A33, B5, B60 and B61. DNA typing for HLA-I class (A, B antigens) by PCR-SSP has high resolution, high specificity, and good reproducibility, which is more suitable for clinical application than serological typing. PCR-SSP may accurately detect the alleles that are easily missed or mistaken in serological typing.

Prehospital endotracheal intubation and chest tubing does not prolong the overall resuscitation time of severely injured patients: a retrospective, multicentre study of the Trauma Registry of the German Society of Trauma Surgery.

PubMed

Kulla, Martin; Helm, Matthias; Lefering, Rolf; Walcher, Felix

2012-06-01

The aim of this study was to determine whether prehospital endotracheal intubation (ETI) and chest tube placement is unnecessarily time consuming in severely injured patients. A retrospective, multicentre study including all adult patients (ISS ≥9; 2002-7) of the Trauma Registry of the German Society of Trauma Surgery who were not secondarily transferred to a trauma centre and received a definitive airway and a chest tube. Creating four groups: AA (n=963) receiving ETI and chest tube on scene, AB (n=1547) ETI performed in the prehospital setting but chest tubing later in the emergency department (ED) and BB (n=640) receiving both procedures in the ED. The BA collective (ETI performed in the ED, but chest tubing on scene) was excluded from the study because of the small sample size (n=41). The trauma resuscitation time (TRT), demographic data, injuries, treatment and outcome of the remaining three collectives were compared. The prehospital TRT of the AA collective was longer than the AB and BB subgroups (80±37 min vs 77±44 min 65±46 min; p<0.01). Although the AA and AB subgroups were more severely injured (ISS 35±15 vs 38±15 vs 31±12; p<0.01) and showed poorer vital parameters on scene, the overall TRT (accident until end of ED treatment) were equal for all three groups (152±59 min vs 151±62 min vs 148±68 min; p=0.07). The TRISS adjusted mortality was also equal in all three groups. In a physician-based emergency medical service, prehospital ETI and chest tube placement do not prolong the total TRT of severely injured patients.

Exploration of polyamide structure-property relationships by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

PubMed

Barrère, Caroline; Rejaibi, Majed; Curat, Aurélien; Hubert-Roux, Marie; Lavanant, Hélène; Afonso, Carlos; Kebir, Nasreddine; Desilles, Nicolas; Lecamp, Laurence; Burel, Fabrice; Loutelier-Bourhis, Corinne

2014-08-15

Polyamides (PA) are among the most used classes of polymers because of their attractive properties. Depending on the nature and proportion of the co-monomers used for their synthesis, they can exhibit a very large range of melting temperatures (Tm ). This study aims at the correlation of data from mass spectrometry (MS) with differential scanning calorimetry (DSC) and X-ray diffraction analyses to relate molecular structure to physical properties such as melting temperature, enthalpy change and crystallinity rate. Six different PA copolymers with molecular weights around 3500 g mol(-1) were synthesized with varying proportions of different co-monomers (amino-acid AB/di-amine AA/di-acid BB). Their melting temperature, enthalpy change and crystallinity rate were measured by DSC and X-ray diffraction. Their structural characterization was carried out by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Because of the poor solubility of PA, a solvent-free sample preparation strategy was used with 2,5-dihydroxybenzoic acid (2,5-DHB) as the matrix and sodium iodide as the cationizing agent. The different proportions of the repeating unit types led to the formation of PA with melting temperatures ranging from 115°C to 185°C. The structural characterization of these samples by MALDI-TOF-MS revealed a collection of different ion distributions with different sequences of repeating units (AA, BB; AB/AA, BB and AB) in different proportions according to the mixture of monomers used in the synthesis. The relative intensities of these ion distributions were related to sample complexity and structure. They were correlated to DSC and X-ray results, to explain the observed physical properties. The structural information obtained by MALDI-TOF-MS provided a better understanding of the variation of the PA melting temperature and established a structure-properties relationship. This work will allow future PA designs to be monitored. Copyright © 2014 John Wiley & Sons, Ltd.

Analysis for genotyping Duffy blood group in inhabitants of Sudan, the Fourth Cataract of the Nile

PubMed Central

2012-01-01

Background Genetic polymophisms of the Duffy antigen receptor for the chemokines (DARC) gene successfully protected against blood stage infection by Plasmodium vivax infection. The Fy (a-, b-) phenotype is predominant among African populations, particularly those originating from West Africa, and it is rare among non-African populations. The aim of this study was to analyse the frequency of four Duffy blood groups based on SNPs (T-33C, G125A, G298A and C5411T) in two local tribes of Sudanese Arabs, the Shagia and Manasir, which are both from the region of the Fourth Nile cataract in Sudan. Methods An analysis of polymorphisms was performed on 217 individuals (126 representatives of the Shagia tribe and 91 of the Manasir). Real-time PCR and TaqMan Genotyping Assays were used to study the prevalence of alleles and genotypes. Results The analysis of allelic and genotype frequency in the T-33C polymorphisms demonstrated a significant dominance of the C allele and CC genotype (OR = 0.53 [0.32-0.88]; p = 0.02) in both tribes. The G125A polymorphism is associated with phenotype Fy(a-, b-) and was identified in 83% of Shagia and 77% of Manasir. With regard to G298A polymorphisms, the genotype frequencies were different between the tribes (p = 0,002) and no single AA homozygote was found. Based on four SNPs examined, 20 combinations of genotypes for the Shagia and Manasir tribes were determined. The genotype CC/AA/GG/CT occurred most often in Shagia tribe (45.9%) but was rare in the Manasir tribe (6.6%) (p < 0.001 Shagia versus Manasir). The FY*AES allele was identified in both analysed tribes. The presence of individuals with the FY*A/FY*A genotype was demonstrated only in the Shagia tribe. Conclusion This is probably the first report showing genotypically Duffy-negative people who carry both FY*BES and FY*AES. The identification of the FY*AES allele in both tribes may be due to admixture of the non-African genetic background. Taken as a whole, allele and genotype frequencies between the Shagia and the Manasir were statistically different. However, the presence of individuals with the FY*A/FY*A genotype was demonstrated only in the Shagia tribe. PMID:22510366

Occurrence of Diverse AbGRI1-Type Genomic Islands in Acinetobacter baumannii Global Clone 2 Isolates from South Korea.

PubMed

Kim, Dae Hun; Jung, Sook-In; Kwon, Ki Tae; Ko, Kwan Soo

2017-02-01

In this study, we analyzed the frequency of the AbGRI1-type genomic island (GI) and its association with genotypes. We obtained 130 Acinetobacter baumannii isolates causing bloodstream infections from patients in South Korea. Antimicrobial susceptibility testing and multilocus sequence typing were performed. The presence of AbGRI1-type GIs and their structures were determined by sequential PCR and sequencing. Ninety-eight isolates (75.3%) representing 14 sequence types (STs) belonged to clonal complex 208 (CC208), corresponding to global clone 2 (GC2). AbGRI1-type GIs interrupted the comM gene in 107 isolates (82.4%). Four types of GIs were identified: Tn6022 (50 isolates; 46.7%), AbaR4 (23 isolates; 21.5%), Tn6166 (10 isolates; 9.3%), and Tn6166/Tn2006 (24 isolates; 22.4%). In the 50 isolates with Tn6022, Tn2006 or Tn2008B, both containing ISAba1-bla OXA-23 , was present in sites other than GIs in 3 or 28 isolates, respectively. In the 10 isolates with Tn6166, Tn2008B was identified in one isolate. AbGRI1-type GIs were identified nearly exclusively in CC208 isolates, with the exception of nine non-CC208 isolates (AbaR4 in eight ST229 isolates and Tn6022 in one ST1244 isolate). Within CC208 isolates, there was evidence of frequent recombination events, in both housekeeping genes and AbGRI1-type GIs, contributing to genotype diversification and the emergence of carbapenem resistance. Copyright © 2017 American Society for Microbiology.

Identification of a conserved B-cell epitope on duck hepatitis A type 1 virus VP1 protein.

PubMed

Wu, Xiaoying; Li, Xiaojun; Zhang, Qingshan; Wulin, Shaozhou; Bai, Xiaofei; Zhang, Tingting; Wang, Yue; Liu, Ming; Zhang, Yun

2015-01-01

The VP1 protein of duck hepatitis A virus (DHAV) is a major structural protein that induces neutralizing antibodies in ducks; however, B-cell epitopes on the VP1 protein of duck hepatitis A genotype 1 virus (DHAV-1) have not been characterized. To characterize B-cell epitopes on VP1, we used the monoclonal antibody (mAb) 2D10 against Escherichia coli-expressed VP1 of DHAV-1. In vitro, mAb 2D10 neutralized DHAV-1 virus. By using an array of overlapping 12-mer peptides, we found that mAb 2D10 recognized phages displaying peptides with the consensus motif LPAPTS. Sequence alignment showed that the epitope 173LPAPTS178 is highly conserved among the DHAV-1 genotypes. Moreover, the six amino acid peptide LPAPTS was proven to be the minimal unit of the epitope with maximal binding activity to mAb 2D10. DHAV-1-positive duck serum reacted with the epitope in dot blotting assay, revealing the importance of the six amino acids of the epitope for antibody-epitope binding. Competitive inhibition assays of mAb 2D10 binding to synthetic LPAPTS peptides and truncated VP1 protein fragments, detected by Western blotting, also verify that LPAPTS was the VP1 epitope. We identified LPAPTS as a VP1-specific linear B-cell epitope recognized by the neutralizing mAb 2D10. Our findings have potential applications in the development of diagnostic techniques and epitope-based marker vaccines against DHAV-1.

Novel genetic markers of the carbonic anhydrase II gene associated with egg production and reproduction traits in Tsaiya ducks.

PubMed

Chang, M-T; Cheng, Y-S; Huang, M-C

2013-02-01

In our previous cDNA microarray study, we found that the carbonic anhydrase II (CA2) gene is one of the differentially expressed transcripts in the duck isthmus epithelium during egg formation period. The aim of this study was to identify the single-nucleotide polymorphisms (SNPs) in the CA2 gene of Tsaiya ducks. The relationship of SNP genotype with egg production and reproduction traits was also investigated. A total of 317 ducks from two lines, a control line with no selection and a selected line, were employed for testing. Three SNPs (C37T, A62G and A65G) in the 3'-untranslated region of the CA2 gene were found. SNP-trait association analysis showed that SNP C37T and A62G were associated with duck egg weight besides fertility. The ducks with the CT and AG genotypes had a 1.46 and 1.62 g/egg lower egg weight as compared with ducks with the CC and AA genotypes, respectively (p < 0.05). But the ducks with CT and AG genotypes had 5.20% and 4.22% higher fertility than those with CC and AA genotypes, respectively (p < 0.05). Diplotype constructed on these three SNPs was associated with duck fertility, and the diplotype H1H4 was dominant for duck fertility. These findings might provide the basis for balanced selection and may be used in marker-assisted selection to improve egg weight and fertility simultaneously in the Tsaiya ducks. © 2012 Blackwell Verlag GmbH.

Interferon-gamma +874 T/A and interleukin-10 -1082 A/G single nucleotide polymorphism in Egyptian children with tuberculosis.

PubMed

Mosaad, Y M; Soliman, O E; Tawhid, Z E; Sherif, D M

2010-10-01

The aim was to investigate the association of interferon-gamma (IFN-γ) +874 T/A and interleukin-10 (IL-10)-1082 A/G single nucleotide polymorphisms with tuberculous infection and post-BCG lymphadenitis in Egyptian children. IFN-γ +874 T/A and IL-10 -1082 A/G polymorphism detection by amplification refractory mutation system technique was carried out for 110 patients with TB, 40 patients with post-BCG lymphadenitis and 118 healthy controls. IFN-γ +874 A allele was higher in TB and post-BCG patients than those in healthy controls (Pc=0.006 and 0.002, respectively). IFN-γ +874 genotype AA was significantly higher in patients with TB than that in control (Pc=0.015), in extrapulmonary than patients with pulmonary TB (PTB) (Pc=0.009), and young children with TB below 5 years (Pc=0.024). No statistically significant differences were observed between patients with TB and controls for the frequency of IL-10(-1082) alleles or genotypes (P>0.05); however, a statistically significant difference in the frequency of IL-10 (-1082) GG genotype was found between patients with pulmonary and extrapulmonary TB (Pc=0.003). Low producer IFN-γ +874 A/A genotype is associated with post-BCG lymphadenitis and TB disease especially in younger children below 5 years. IL-10-1082 G/G genotype did not exhibit significant association except for increased GG frequency in PTB. Both cytokine polymorphisms have no relation to tuberculin reaction in patients with TB. © 2010 The Authors. Scandinavian Journal of Immunology © 2010 Blackwell Publishing Ltd.

Do Biochemical Markers and Apa I Polymorphism in IGF-II Gene Play a Role in the Association of Birth Weight and Later BMI?

PubMed

Wu, Junqing; Ren, Jingchao; Li, Yuyan; Wu, Yinjie; Gao, Ersheng

2013-01-01

The aim of the study was to explore the mechanisms underlying the association of birth weight with later body mass index (BMI) from the biochemical markers related to metabolism and the Apa I polymorphism in IGF-II gene. A total of 300 children were selected randomly from the Macrosomia Birth Cohort in Wuxi, China. The height and weight were measured and blood samples were collected. Plasma concentrations of 8 biochemical markers were detected. Apa I polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Biochemical markers were detected for 296 subjects and 271 subjects were genotyped for the Apa I polymorphism. No association was found between birth weight and 8 biochemical markers. In boys, the BMIs of AA, AG and GG genotypes were 16.10 ± 2.24 kg/m(2), 17.40 ± 3.20 kg/m(2), 17.65 ± 2.66 kg/m(2). And there was statistical difference among the three genotypes. But in girls, there was no statistical difference. The birth weights of AA, AG and GG genotypes were 3751.13 ± 492.43 g, 3734.00 ± 456.88 g, 3782.00 ± 461.78 g. And there was no statistical difference among the three genotypes. Biochemical markers are not associated with birth weight. Apa I polymorphism may be related to childhood BMI, but it may be not associated with birth weight. Therefore, biochemical markers and Apa I polymorphism might not play a role in the association of birth weight and BMI.

A critical functional missense mutation (H173R) in the bovine PROP1 gene significantly affects growth traits in cattle.

PubMed

Pan, Chuanying; Wu, Chongyang; Jia, Wenchao; Xu, Yao; Lei, Chuzhao; Hu, Shenrong; Lan, Xianyong; Chen, Hong

2013-12-01

The PROP1 protein, encoded by the prophet of Pit-1 (PROP1) gene, exhibits both DNA-binding and transcriptional activation abilities. Its expression leads to the ontogenesis of growth hormone (GH), prolactin (PRL), thyroid-stimulating hormone (TSH), and pituitary hormone. The missense mutation H173R in PROP1 may result in deficiencies of GH, PRL, TSH, and Pit-1, thereby affecting growth traits. The objective of this study was to characterize the H173R mutation within the PROP1 gene and examine its associations with growth traits in cattle. Accordingly, the H173R mutation was genotyped in 1207 cows belonging to five Chinese native breeds. Three genotypes were identified among the specimens, with genotype AA being the major one. Consequently, the "G" allele was the minor allele. Association testing revealed that the H173R mutation was significantly associated with body weight, average daily weight gain and physical parameters in the analyzed breeds. Interestingly, the cows with genotype AG and/or AA had superior growth traits compared with those expressing the GG genotype, in all tested breeds. These findings revealed that the "A" allele had positive effects on growth traits, which was consistent with the increasing binding ability and enhanced activation capacity associated with the bovine isoform PROP1-173H, representing the "A" allele. Therefore, the H173R mutation can be considered as a DNA marker for selecting individuals with superior growth traits, thereby contributing to research on breeding and genetics in the beef industry. © 2013.

GC Gene Polymorphisms and Vitamin D-Binding Protein Levels Are Related to the Risk of Generalized Aggressive Periodontitis

PubMed Central

Song, Wenli; Wang, Xian'e; Tian, Yu; Zhang, Xin; Lu, Ruifang

2016-01-01

Objective. To explore whether GC (group-specific component) rs17467825, rs4588, and rs7041 polymorphisms are associated with generalized aggressive periodontitis. Methods. This case-control study recruited 372 patients with generalized aggressive periodontitis (group AgP) and 133 periodontal healthy subjects (group HP). GC rs17467825, rs4588, and rs7041 genotypes and plasmatic vitamin D-binding protein (DBP) were measured. Analysis of single SNP and multiple SNPs was performed and relevance between plasmatic DBP and haplotypes was analyzed. Results. GC rs17467825 GG genotype was statistically associated with lower risk for generalized aggressive periodontitis under the recessive model (OR = 0.52, 95% CI: 0.30–0.92, p = 0.028). GC rs17467825 and rs4588 had strong linkage disequilibrium with r 2 ≥ 0.8 and D′ ≥ 0.8. Haplotype (GC rs17467825, rs4588) GC was associated with the less risk for generalized aggressive periodontitis (OR = 0.29, 95% CI: 0.09–0.96, p = 0.043). In group AgP, individuals with combined genotype (GC rs17467825, rs4588) AG+CA had significantly lower plasmatic DBP level than those with the other two combined genotypes (AG+CA versus AA+CC p = 0.007; AG+CA versus GG+AA p = 0.026). Conclusions. GC rs17467825 genotype GG and haplotype (GC rs17467825, rs4588) GC are associated with generalized aggressive periodontitis. The association may be acquired through regulating DBP levels. The functions of GC gene and DBP in inflammatory disease need to be further studied. PMID:28018430

Association of TNF-α 308 G/A Polymorphism With Type 2 Diabetes: A Case–Control Study in the Iranian Kurdish Ethnic Group

PubMed Central

Golshani, Hasan; Haghani, Karimeh; Dousti, Majid; Bakhtiyari, Salar

2015-01-01

Objectives Tumor necrosis factor-α (TNF-α) plays roles in the development of obesity, insulin resistance, and possibility of Type 2 diabetes mellitus (T2DM). The objective of the current study was to evaluate the association of TNF-α promoter−308 G/A polymorphism with T2DM. Methods In all, 1038 patients with T2DM and 1023 normoglycemic controls were included in this study. All participants were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. Genotypic and allelic frequencies were then analyzed in each group. Serum lipids, fasting glucose, fasting serum insulin, homeostatic model assessment of insulin resistance, and hemoglogin A1c levels were determined by conventional methods. Results The allelic frequency of the A allele was significantly different between case and control participants (p = 0.006). Genotypes GA and AA were found to be significantly associated with 2.24- and 3.18-fold increased risk for T2DM, respectively. Similarly, the dominant model of -308 G/A polymorphism was found to have a higher risk for T2DM (odds ratio = 2.34, p = 0.001). Individuals with T2DM carrying the GA + AA genotypes of -308 G/A variation had significantly lower fasting plasma insulin than those carrying GG genotype. Conclusion Our findings revealed that there is an association between the TNF-α promoter -308 G/A polymorphism and T2DM in this population. PMID:25938018

Association of TNF-α 308 G/A Polymorphism With Type 2 Diabetes: A Case-Control Study in the Iranian Kurdish Ethnic Group.

PubMed

Golshani, Hasan; Haghani, Karimeh; Dousti, Majid; Bakhtiyari, Salar

2015-04-01

Tumor necrosis factor-α (TNF-α) plays roles in the development of obesity, insulin resistance, and possibility of Type 2 diabetes mellitus (T2DM). The objective of the current study was to evaluate the association of TNF-α promoter-308 G/A polymorphism with T2DM. In all, 1038 patients with T2DM and 1023 normoglycemic controls were included in this study. All participants were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. Genotypic and allelic frequencies were then analyzed in each group. Serum lipids, fasting glucose, fasting serum insulin, homeostatic model assessment of insulin resistance, and hemoglogin A1c levels were determined by conventional methods. The allelic frequency of the A allele was significantly different between case and control participants (p = 0.006). Genotypes GA and AA were found to be significantly associated with 2.24- and 3.18-fold increased risk for T2DM, respectively. Similarly, the dominant model of -308 G/A polymorphism was found to have a higher risk for T2DM (odds ratio = 2.34, p = 0.001). Individuals with T2DM carrying the GA + AA genotypes of -308 G/A variation had significantly lower fasting plasma insulin than those carrying GG genotype. Our findings revealed that there is an association between the TNF-α promoter -308 G/A polymorphism and T2DM in this population.

Evaluation of PCSK9 levels and its genetic polymorphisms in women with polycystic ovary syndrome.

PubMed

Xavier, Luana B; Sóter, Mirelle O; Sales, Mariana F; Oliveira, Daisy K; Reis, Helton J; Candido, Ana L; Reis, Fernando M; Silva, Ieda O; Gomes, Karina B; Ferreira, Cláudia N

2018-02-20

Dyslipidemia is one of the common metabolic disorders in Polycystic Ovary Syndrome (PCOS). Proprotein convertase subtilisin kexin type 9 (PCSK9) is a new component of lipid metabolism and correlated to the development of dyslipidemia and atherosclerosis. This protein acts by preventing the recycling of LDL receptors (LDL-r) back to the cell surface and thus generates higher levels of LDLc. The objective of this study was to evaluate the PCSK9 polymorphisms rs505151 (c.2009A>G), rs562556 (c.1420A>G) and rs11206510 (T>C) and plasma PCSK9 levels in PCOS. A group of women with PCOS (n=97), and a group of healthy women (control, n=99) were selected. Biochemical parameters were determined by using Vitros system and polymorphisms were assessed by TaqMan SNP Genotyping Assays. Plasma PCSK9 levels or PCSK9 polymorphisms were not associated with PCOS. The genotype rs11206510TT was associated with higher levels of PCSK9 in both groups. The population investigated (PCOS+control groups) with the rs505151AA genotype presented higher HDLc levels. The GG genotype regarding rs562556 polymorphism was associated with higher HDLc in PCOS group, while the AA genotype carriers had higher plasma testosterone levels when evaluated all women in a same group. The results were the same by comparing recessive and dominant model despite PCOS or both groups altogether. Our results suggest that PCSK9 is not altered specifically in PCOS, but it could be associated with in lipid and androgen metabolism in Brazilian women. Copyright © 2017 Elsevier B.V. All rights reserved.

Hepatitis B virus sero-profiles and genotypes in HIV-1 infected and uninfected injection and Non-injection drug users from coastal Kenya.

PubMed

Webale, Mark K; Kilongosi, Mark W; Budambula, Valentine; Lihana, Raphael; Musumba, Francis O; Nyamache, Anthony K; Budambula, Nancy L M; Ahmed, Aabid A; Ouma, Collins; Were, Tom

2015-07-30

Information about HBV sero-markers, infection stages and genotypes in HIV-1 infected and uninfected injection and non-injection drug users (IDUs) in Kenya remains elusive. A cross-sectional study examining HBV sero-marker, infection stages and genotypes was conducted among HIV-1 infected and uninfected, respectively, IDUs (n = 157 and n = 214) and non-IDUs (n = 139 and n = 48), and HIV-1 uninfected non-drug using controls (n = 194) from coastal, Kenya. HBV sero-marker and infection stages were based on HBV 5-panel rapid test plasma sero-reactivity. DNA was extracted from acute and chronic plasma samples and genotypes established by nested-PCR and direct sequencing. HBsAg positivity was higher in HIV-1 infected IDUs (9.6%) relative to HIV-1 uninfected IDUs (2.3%), HIV-1 infected non-IDUs (3.6%), HIV-1 uninfected non-IDUs (0.0%) and non-drug users (2.6%; P = 0.002). Contrastingly, HBsAb positivity was higher in HIV-1 uninfected IDUs (14.6%) and non-IDUs (16.8) in comparison to HIV-1 infected IDUs (8.3%), and non-IDUs (8.6%), and non-drug users (8.2%; P = 0.023). HBcAb positivity was higher in HIV-1 infected IDUs (10.2%) compared to HIV-1 uninfected IDUs (3.3%), HIV-1 infected non-IDUs (6.5%), HIV-1 uninfected non-IDUs (2.1%) and non-drug users (4.6%; P = 0.038). Acute (5.7%, 1.4%, 0.0%, 0.0% and 1.5%) and chronic (5.1%, 0.9%, 3.6%, 0.0% and 1.5%) stages were higher in HIV-1 infected IDUs, compared to HIV-1 uninfected IDUs, HIV-1 infected and uninfected non-IDUs and non-drug users, respectively. However, vaccine type response stage was higher in HIV-1 uninfected IDUs (15.4%) relative to HIV-1 infected IDUs (6.4%), and HIV-1 infected (6.5%), and uninfected (10.4%) non-IDUs, and non-drug users (5.7%; P = 0.003). Higher resolved infection rates were also recorded in HIV-1 uninfected IDUs (11.2%) compared to HIV-1 infected IDUs (8.3%), and HIV-1 infected (7.2%), uninfected (6.3%) non-IDUs, and non-drug users (6.7%; P = 0.479), respectively. Only A1 genotype showing minimal diversity was detected among the study participants. HBV sero-markers and infection staging are valuable in diagnosis and genotyping of HBV infections. Among IDUs, higher HBsAg and HBcAb positivity in HIV-1 infected and higher HBsAb positivity in HIV-1 negative IDUs suggests frequent exposure. Additionally, HBV genotype A is the dominant circulating genotype in both high and low risk populations of Kenya.

Two zebrafish G2A homologs activate multiple intracellular signaling pathways in acidic environment.

PubMed

Ichijo, Yuta; Mochimaru, Yuta; Azuma, Morio; Satou, Kazuhiro; Negishi, Jun; Nakakura, Takashi; Oshima, Natsuki; Mogi, Chihiro; Sato, Koichi; Matsuda, Kouhei; Okajima, Fumikazu; Tomura, Hideaki

2016-01-01

Human G2A is activated by various stimuli such as lysophosphatidylcholine (LPC), 9-hydroxyoctadecadienoic acid (9-HODE), and protons. The receptor is coupled to multiple intracellular signaling pathways, including the Gs-protein/cAMP/CRE, G12/13-protein/Rho/SRE, and Gq-protein/phospholipase C/NFAT pathways. In the present study, we examined whether zebrafish G2A homologs (zG2A-a and zG2A-b) could respond to these stimuli and activate multiple intracellular signaling pathways. We also examined whether histidine residue and basic amino acid residue in the N-terminus of the homologs also play roles similar to those played by human G2A residues if the homologs sense protons. We found that the zG2A-a showed the high CRE, SRE, and NFAT activities, however, zG2A-b showed only the high SRE activity under a pH of 8.0. Extracellular acidification from pH 7.4 to 6.3 ameliorated these activities in zG2A-a-expressing cells. On the other hand, acidification ameliorated the SRE activity but not the CRE and NFAT activities in zG2A-b-expressing cells. LPC or 9-HODE did not modify any activity of either homolog. The substitution of histidine residue at the 174(th) position from the N-terminus of zG2A-a to asparagine residue attenuated proton-induced CRE and NFAT activities but not SRE activity. The substitution of arginine residue at the 32nd position from the N-terminus of zG2A-a to the alanine residue also attenuated its high and the proton-induced CRE and NFAT activities. On the contrary, the substitution did not attenuate SRE activity. The substitution of the arginine residue at the 10th position from the N-terminus of zG2A-b to the alanine residue also did not attenuate its high or the proton-induced SRE activity. These results indicate that zebrafish G2A homologs were activated by protons but not by LPC and 9-HODE, and the activation mechanisms of the homologs were similar to those of human G2A. Copyright © 2015 Elsevier Inc. All rights reserved.

Electron Detachment Dissociation (EDD) of Fluorescently Labeled Sialylated Oligosaccharides

PubMed Central

Zhou, Wen; Håkansson, Kristina

2012-01-01

We explored the application of electron detachment dissociation (EDD) and infrared multiphoton dissociation (IRMPD) tandem mass spectrometry to fluorescently labeled sialylated oligosaccharides. Standard sialylated oligosaccharides and a sialylated N-linked glycan released from human transferrin were investigated. EDD yielded extensive glycosidic cleavages and cross-ring cleavages in all cases studied, consistently providing complementary structural information compared to IRMPD. Neutral losses and satellite ions such as C – 2H ions were also observed following EDD. In addition, we examined the influence of different fluorescent labels. The acidic label 2-aminobenzoic acid (2-AA) enhanced signal abundance in negative-ion mode. However, few cross-ring fragments were observed for 2-AA labeled oligosaccharides. The neutral label 2-aminobenzamide (2-AB) resulted in more cross-ring cleavages compared to 2-AA labeled species, but not as extensive fragmentation as for native oligosaccharides, likely resulting from altered negative charge locations from introduction of the fluorescent tag. PMID:22120881

Testicular size at weaning in tropically-adapted beef bulls as influenced by breed of sire and dam.

PubMed

Browning, R; Warrington, B G; Holloway, J W; Randel, R D

1997-07-15

This study was conducted to evaluate testicular size at weaning for bulls representing diverse tropically-adapted genotypes. Calves from 2 locations were weighed and castrated at weaning. In one herd, calves were born to Brahman dams and Angus, Tuli, and Brahman sires. Body weights and paired testes weights were heavier (P < 0.01) for Angus x Brahman (AB) genotype than for Tuli x Brahman (TB) and purebred Brahman (BB) genotype calves. The testes:body weight ratio was greater (P < 0.01) for AB than for TB and BB calves. In a second herd, calves were born to Angus cows and Brahman, Tuli, and Senepol sires. Means were similar between Brahman- (BA), Tuli-(TA), and Senepol-sired (SA) calves for body weight and testes:body weight ratio. Paired testes weight was heavier (P < 0.05) for SA than BA calves. Across locations, paired testes weights were heavier (P < 0.01) for TA than TB calves but their body weights were similar. Within-herd deviations were greater (P < 0.01) for AB than BA calves for paired testes weight and testes:body weight ratio. The correlation between the proportion of Bos indicus genetic contribution and testes:body weight ratio was significantly negative. Tropically-adapted calves differed in testicular size at weaning due to breed of sire and dam effects.

WatAA: Atlas of Protein Hydration. Exploring synergies between data mining and ab initio calculations.

PubMed

Černý, Jiří; Schneider, Bohdan; Biedermannová, Lada

2017-07-14

Water molecules represent an integral part of proteins and a key determinant of protein structure, dynamics and function. WatAA is a newly developed, web-based atlas of amino-acid hydration in proteins. The atlas provides information about the ordered first hydration shell of the most populated amino-acid conformers in proteins. The data presented in the atlas are drawn from two sources: experimental data and ab initio quantum-mechanics calculations. The experimental part is based on a data-mining study of a large set of high-resolution protein crystal structures. The crystal-derived data include 3D maps of water distribution around amino-acids and probability of occurrence of each of the identified hydration sites. The quantum mechanics calculations validate and extend this primary description by optimizing the water position for each hydration site, by providing hydrogen atom positions and by quantifying the interaction energy that stabilizes the water molecule at the particular hydration site position. The calculations show that the majority of experimentally derived hydration sites are positioned near local energy minima for water, and the calculated interaction energies help to assess the preference of water for the individual hydration sites. We propose that the atlas can be used to validate water placement in electron density maps in crystallographic refinement, to locate water molecules mediating protein-ligand interactions in drug design, and to prepare and evaluate molecular dynamics simulations. WatAA: Atlas of Protein Hydration is freely available without login at .

[Interleukin-10-1082 promoter polymorphism and the risk of gastric cancer].

PubMed

Yin, Yi-qiong; Liu, Chun-juan; Zhang, Ming-ming; Zhou, Yong

2012-05-01

To investigate the association between Interleukin-10 (IL-10) promoter polymorphism and the gastric cancer risk in Chinese Han patients. DNA was extracted from blood samples of gastric cancer patients (n = 75) and controls (n = 75). IL-10 -1082 promoter polymorphism in both patient and control group (three genotypes distribution: AA, AG and GG) was identified by PCR-RFLP and its relationship with gastric cancer risk, clinic and pathologic features was also analyzed. Patients with gastric cancer had a significantly lower frequency of AA (OR = 0.43, 95% CI = 0.20, 0.92; P = 0.03) than controls. Patients with proximal gastric cancer had a significantly higher frequency of GG (OR = 3.06, 95% CI = 1.12, 8.36; P = 0.03) than those with distant gastric cancer. Patients with advanced (stage II/IV) gastric cancer had a significantly higher frequency of AA (OR = 5.09, 95% CI = 1.05, 24.70; P = 0.04) than those with early (stage I /IV) gastric cancer. When stratified by the Lauren's classification, histological differentiation of gastric cancer, no statistically significant results was observed. This study suggests that the IL-1 1082 promoter polymorphism may be associated with gastric cancer in Chinese Han patients, and the difference in genotype distribution may be associated with the location and stage of gastric cancer.

Phenolic composition and free radical scavenging activity of different apple varieties in relation to the cultivar, tissue type and storage.

PubMed

Carbone, K; Giannini, B; Picchi, V; Lo Scalzo, R; Cecchini, F

2011-07-15

The aim of this research was to evaluate the influence of genotype, tissue type and cold storage on the bioactive compounds content and on the antiradical activity (AA) of different apple cultivars (Golden cl. B, Fuji cl. Kiku8, Braeburn cl. Hillwell). The content of analysed phyto-compounds depended on the clone, on the part of fruit, and to a minor extent, on the storage. For EC(50) data, the cultivar represented the main source of variation and the interaction with the type of tissue, was significant. The AA of apples, measured by means of the DPPH test, was highly correlated to the flavan-3-ols content, which represents a good predictor of the apple antiradical power. The new Braeburn's clone, the Hillwell, had the worst AA related to a minor phyto-chemical content. Also, its phenolic content was dramatically reduced after cold storage (flesh: -50%; peels: -20%; p<0.05). Obtained results underlined the key role of the genotype on the content of the nutraceutical power of apples, which is important to improve their quality and consumption benefits, suggesting to the breeders to pay more attention to the potential healthy compounds in the development of new hybrids. Copyright © 2011 Elsevier Ltd. All rights reserved.

Impact of interleukin-10 polymorphisms (-1082 and -3575) on the survival of patients with lymphoid neoplasms.

PubMed

Domingo-Domènech, Eva; Benavente, Yolanda; González-Barca, Eva; Montalban, Carlos; Gumà, Josep; Bosch, Ramón; Wang, Sophia S; Lan, Qing; Whitby, Denise; Fernández de Sevilla, Alberto; Rothman, Nathaniel; de Sanjosé, Sílvia

2007-11-01

Single-nucleotide polymorphisms (SNP) in interleukin-10 (IL-10) genes can influence immune responses, which may affect the outcome of patients with lymphoid neoplasms. The aim of this study was to explore the association between polymorphisms of IL-10-(1082A>G) and IL-10-(3575T>A) with the overall survival in patients with lymphoid neoplasms. We analyzed two IL-10 SNP (-1082 and -3575) in 472 consecutive cases with lymphoid neoplasms. Genotypes were tested for association with overall survival and classical prognostic factors by multivariate analysis. Haplotype analysis was carried out using the haplostats package implemented in R software. The implications for survival of patients with lymphoma were evaluated using multivariate analysis. Lymphoma patients with the IL-10-(3575T>A) genotype had a better overall survival (p= 0.002), as did the subgroup with non-Hodgkin's lymphoma (NHL) (p=0.05). Patients with the IL10(-1082GG) genotype had a better median overall survival (p=0.05). When both genotypes were included in a multivariate analysis, IL-10(-3575AA) genotype was the only independent prognostic factor for survival (HR=0.20, 95%CI 0.05-0.92). Patients with the IL-10(-1082) and (-3575) G-A/G-A diplotype had a longer overall survival (p=0.003) and this combination appeared to be an independent prognostic factor for survival (HR:0.26; 95%CI 0.08-0.83). The IL-10(-3575A/A) genotype was identified as a marker of favorable survival. Because the IL-10(-1082) and (-3575) G-A/G-A diplotype was also identified as an indicator of longer survival, we cannot exclude the potential additive role of the IL-10(-1082GG) genotype. These results need to be replicated in larger series and examined in different NHL subtypes.

Variation in the ACE, PPARGC1A and PPARA genes in Lithuanian football players.

PubMed

Gineviciene, Valentina; Jakaitiene, Audrone; Tubelis, Linas; Kucinskas, Vaidutis

2014-01-01

The aim of this study was to determine the impact of ACE (I/D), PPARGC1A (G/A) and PPARA (G/C) polymorphisms on footballers performance among 199 Lithuanian professional footballers and 167 sedentary, healthy men (controls). Genotyping was performed using polymerase chain reaction and restriction fragment length polymorphism methods on DNA from leucocytes. Results revealed that the angiotensin-1-coverting enzyme gene (ACE) genotype distribution was significantly different between total football players group (II 23.6%, ID 46.7% and DD 29.6%) and the controls (II 24.6%, ID 29.9% and DD 45.5%; P=0.002). Although investigating PPARGC1A (G/A) and PPARA (G/C) polymorphisms no significant results were obtained in the total football players group, however, significant differences were determined between forwards and controls [PPARGC1A: GG 54.6%, GA 29.5%, AA 15.9% vs. GG 49.7%, GA 44.3% and AA 6.0% (P = 0.044); PPARA: GG 52.3%, GC 40.9%, CC 6.8% vs. GG 72.4%, GC 24.6% and CC 3.0% (P = 0.034)]. In the whole cohort, the odds ratio of the genotype [ACE ID + PPARA GG] being a footballer was 1.69 (95% CI 1.04-2.74), and of [ACE ID + PPARGC1A GG] 1.93 (95% CI 1.10-3.37) and of [ACE II + PPARA GC] 2.83 (95% CI 1.02-7.91) compared to controls. It was revealed that ACE ID genotype together with PPARA GG and PPARGC1A GG as well as ACE II genotype with PPARA GC is probably the 'preferable genotype' for footballers. Summing up, the present study suggests that the ACE, PPARGC1A and PPARA polymorphisms genotypes are associated, separately and in combination, with Lithuanian footballers' performance.

G Allele of the IGF2 ApaI Polymorphism Is Associated With Judo Status.

PubMed

Itaka, Toshio; Agemizu, Kenichiro; Aruga, Seiji; Machida, Shuichi

2016-07-01

Itaka, T, Agemizu, K, Aruga, S, and Machida, S. G allele of the IGF2 ApaI polymorphism is associated with judo status. J Strength Cond Res 30(7): 2043-2048, 2016-Previous studies have reported that the insulin-like growth factor 2 (IGF2) ApaI polymorphism is associated with body mass index, fat mass, and grip strength. Competitive judo requires high levels of strength and power. The purpose of this study was to investigate the association between the IGF2 ApaI and ACTN3 R577X polymorphisms and judo status. The subjects were 156 male judo athletes from a top-level university in Japan. They were divided into 3 groups based on their competitive history: international-level athletes, national-level athletes, and others. Genomic DNA was extracted from the saliva of each athlete, and the maximal isometric strength of the trunk muscles and handgrip strength were measured. Genotyping by polymerase chain reaction-restriction fragment length polymorphism was used to detect IGF2 (rs680) and α-actinin-3 (ACTN3) (rs1815739) gene polymorphisms. The genotype frequencies of the 2 gene polymorphisms were compared among the 3 groups of judo athletes and controls. International-level judo athletes showed a higher frequency of the GG + GA genotype of the IGF2 gene than that of the national-level athletes and others. There was an inverse linear correlation between the frequency of the IGF2 AA genotype and level of judo performance (p = 0.041). Back muscle strength relative to height and weight was higher in subjects with the GG + GA genotype than in those with the AA genotype. Conversely, the ACTN3 R577X polymorphism was not associated with judo status. Additionally, no differences were found in back muscle or handgrip strength among the ACTN3 genotypes. In conclusion, the results indicate that the IGF2 gene polymorphism may be associated with judo status.

Influence of TS (rs34743033) and RUNX1 (rs2014300) gene polymorphisms on survival outcomes of fluorouracil-based chemotherapy in Chinese advanced gastric cancer patients.

PubMed

Han, Rongbo; Wei, Jingsun; Zhang, Honghong; Su, Xinyu; Chu, Xia; Chen, Yuetong; Gong, Yang; Wang, Xiujuan; Shi, Junfeng; Chen, Jinfei

2018-01-01

This study aimed to explore the clinical correlation of single-nucleotide polymorphisms of thymidylate synthase (TS) and runt-related transcription factor 1 (RUNX1) in patients with postoperative stage II and III gastric cancer (GC). Samples were obtained from 661 patients with postoperative stage II and III GC. TS (rs34743033) and RUNX1 (rs2014300) were genotyped in 261 patients who received postoperative basic platinum and fluorouracil chemotherapy regimens and 400 patients who did not accept chemotherapy. TS (rs34743033) variant genotypes significantly prolonged the median overall survival (OS) time compared to the patients who only received adjuvant chemotherapy (HR 1.604, 95% CI 1.068-2.410, p =0.021). Moreover, 3R/3R variant genotypes were demonstrated to have a positive effect on the OS of patients who received chemotherapy based on cisplatin (HR 1.754, 95% CI 1.041-2.954, p =0.031) compared to oxaliplatin. A stratification analysis indicated that 2R/3R and 2R/2R variant genotypes were associated with inferior survival in GC patients with intestinal-type tumors, tumor less than 5 cm in size, and poorly differentiated tumors ( p <0.05). However, RUNX1 (rs2014300) AA genotypes markedly increased the risk of death in GC patients compared with the GG/GA genotypes ( p =0.007), but no significant difference was observed between chemotherapy based on platinum. The stratification analysis showed that the GA/AA genotype was significantly associated with inferior survival in well to moderately differentiated tumors (HR 2.001, 95% CI 1.082-3.703, p =0.023). These preliminary results indicated that the two polymorphisms had a significant effect on postoperative adjuvant chemotherapy. TS (rs34743033) and RUNX1 (rs2014300) may be used as biomarkers to predict prognosis and select chemotherapy regimens in GC patients.

78 FR 44265 - Unified Agenda of Federal Regulatory and Deregulatory Actions

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-23

... . RIN: 1625-AB27 184. Marine Vapor Control Systems Legal Authority: 33 U.S.C. 1225; 42 U.S.C. 7511b(f)(2... facility and vessel vapor control systems (VCSs). The proposed changes would make VCS requirements more... Requirements for 1625-AA99 Notices of Arrival and Departure, and Automatic Identification System. 182...

75 FR 3615 - Airworthiness Directives; Agusta S.p.A. (Agusta) Model AB139 and AW139 Helicopters

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-22

...; Directorate Identifier 2009-SW-50-AD; Amendment 39-16129; AD 2009-19-51] RIN 2120-AA64 Airworthiness... document publishes in the Federal Register an amendment adopting Airworthiness Directive (AD) 2009-19-51... debonding area exceeds a certain limit, repairing the tailboom. This AD results from a mandatory continuing...

Torrejon AB, Spain. Revised Uniform Summary of Surface Weather Observations. Parts A-F.

DTIC Science & Technology

1987-08-13

OF SURFACE WEATHER OBSERVATIONS Q IORREJON AB SPAIN MSC 082270 N 40 29 W 003 27 ELEV 1994 FT LETO PARTS A F HOURS SUMMARIZED 0000 - 2300 LST PERIOD OF...8217I ..5 .8? .11 ..1 I14*! .0? .fl .0. .00 TgvC( TRACE .30 1.3 • . I *=I" i.1?i . o’, . 35 .tIU .’ uC .,0 .0O0 .qurl...MAC TA TION NUMPLR: OP227:) STATION NAME: TORREJON AR SPAIN PERIOD OF RLCORD: 7A-A? MONT-: FES 6OUQS(LSTI: 1’. UC -I1UO I WIND SPEED IN KNOTS

Is Increased Susceptibility to Balkan Endemic Nephropathy in Carriers of Common GSTA1 (*A/*B) Polymorphism Linked with the Catalytic Role of GSTA1 in Ochratoxin A Biotransformation? Serbian Case Control Study and In Silico Analysis

PubMed Central

Reljic, Zorica; Zlatovic, Mario; Savic-Radojevic, Ana; Pekmezovic, Tatjana; Djukanovic, Ljubica; Matic, Marija; Pljesa-Ercegovac, Marija; Mimic-Oka, Jasmina; Opsenica, Dejan; Simic, Tatjana

2014-01-01

Although recent data suggest aristolochic acid as a putative cause of Balkan endemic nephropathy (BEN), evidence also exists in favor of ochratoxin A (OTA) exposure as risk factor for the disease. The potential role of xenobiotic metabolizing enzymes, such as the glutathione transferases (GSTs), in OTA biotransformation is based on OTA glutathione adducts (OTHQ-SG and OTB-SG) in blood and urine of BEN patients. We aimed to analyze the association between common GSTA1, GSTM1, GSTT1, and GSTP1 polymorphisms and BEN susceptibility, and thereafter performed an in silico simulation of particular GST enzymes potentially involved in OTA transformations. GSTA1, GSTM1, GSTT1 and GSTP1 genotypes were determined in 207 BEN patients and 138 non-BEN healthy individuals from endemic regions by polymerase chain reaction (PCR). Molecular modeling in silico was performed for GSTA1 protein. Among the GST polymorphisms tested, only GSTA1 was significantly associated with a higher risk of BEN. Namely, carriers of the GSTA1*B gene variant, associated with lower transcriptional activation, were at a 1.6-fold higher BEN risk than those carrying the homozygous GSTA1*A/*A genotype (OR = 1.6; p = 0.037). In in silico modeling, we found four structures, two OTB-SG and two OTHQ-SG, bound in a GSTA1 monomer. We found that GSTA1 polymorphism was associated with increased risk of BEN, and suggested, according to the in silico simulation, that GSTA1-1 might be involved in catalyzing the formation of OTHQ-SG and OTB-SG conjugates. PMID:25111321

Two cases of maternal alloimmunization against human neutrophil alloantigen-4b, one causing severe alloimmune neonatal neutropenia.

PubMed

Curtis, Brian R; Roman, Ashley S; Sullivan, Mia J; Raven, Cindy S; Larison, Judy; Weitekamp, Lee Ann

2016-01-01

Human neutrophil antigen (HNA)-4a/4bw is encoded by 230G>A in ITGAM, which results in an Arg61His substitution of the αM chain (CD11b) of complement receptor 3 (CR3; CD11b/18 or Mac-1). HNA-4a antibodies have been detected in the sera of female blood donors and in maternal sera that caused alloimmune neonatal neutropenia (ANN), in which maternal immunoglobulin (Ig)G antibodies against a paternally inherited HNA cross the placenta and destroy fetal and neonatal neutrophils. However, to date, antibodies specific for HNA-4b have not been reported. Here, we report the first two examples of HNA-4b antibodies. The two sera studied were both from previously pregnant females, one a multiparous female blood donor implicated in two separate transfusion reactions and the second a mother whose first pregnancy resulted in the birth of a severely neutropenic (0 × 10(6) neutrophils/L) infant affected with ANN. Serum neutrophil antibody testing was by flow cytometry and CD11b/18 monoclonal antibody immobilization of granulocyte antigens assay, and HNA genotyping was performed by polymerase chain reaction with sequence-specific priming and allele-specific 5' exonuclease assays. Sera from both women contained IgG antibodies reactive only with HNA-4b+ neutrophils and both typed HNA-4a/a. Both were immunized through pregnancy since their husbands and children all typed HNA-4a/b. The serologic results, together with the genotype results, confirm that these are the first reported cases of neutrophil antibodies specific for HNA-4b. © 2015 AABB.

HHEX_23 AA Genotype Exacerbates Effect of Diabetes on Dementia and Alzheimer Disease: A Population-Based Longitudinal Study

PubMed Central

Xu, Wei-Li; Pedersen, Nancy L.; Keller, Lina; Kalpouzos, Grégoria; Wang, Hui-Xin; Graff, Caroline; Winblad, Bengt; Bäckman, Lars; Fratiglioni, Laura

2015-01-01

Background Research has suggested that variations within the IDE/HHEX gene region may underlie the association of type 2 diabetes with Alzheimer disease (AD). We sought to explore whether IDE genes play a role in the association of diabetes with dementia, AD, and structural brain changes using data from two community-based cohorts of older adults and a subsample with structural MRI. Methods and Findings The first cohort, which included dementia-free adults aged ≥75 y (n = 970) at baseline, was followed for 9 y to detect incident dementia (n = 358) and AD (n = 271) cases. The second cohort (for replication), which included 2,060 dementia-free participants aged ≥60 y at baseline, was followed for 6 y to identify incident dementia (n = 166) and AD (n = 121) cases. A subsample (n = 338) of dementia-free participants from the second cohort underwent MRI. HHEX_23 and IDE_9 were genotyped, and diabetes (here including type 2 diabetes and prediabetes) was assessed. In the first cohort, diabetes led to an adjusted hazard ratio (HR) of 1.73 (95% CI 1.19–2.32) and 1.66 (95% CI 1.06–2.40) for dementia and AD, respectively, among all participants. Compared to people carrying the GG genotype without diabetes, AA genotype carriers with diabetes had an adjusted HR of 5.54 (95% CI 2.40–7.18) and 4.81 (95% CI 1.88–8.50) for dementia and AD, respectively. There was a significant interaction between HHEX_23-AA and diabetes on dementia (HR 4.79, 95% CI 1.63–8.90, p = 0.013) and AD (HR 3.55, 95% CI 1.45–9.91, p = 0.025) compared to the GG genotype without diabetes. In the second cohort, the HRs were 1.68 (95% CI 1.04–2.99) and 1.64 (1.02–2.33) for the diabetes–AD and dementia–AD associations, respectively, and 4.06 (95% CI 1.06–7.58, p = 0.039) and 3.29 (95% CI 1.02–8.33, p = 0.044) for the interactions, respectively. MRI data showed that HHEX_23-AA carriers with diabetes had significant structural brain changes compared to HHEX_23-GG carriers without diabetes. No joint effects of IDE_9 and diabetes on dementia were shown. As a limitation, the sample sizes were small for certain subgroups. Conclusions A variant in the HHEX_23 gene interacts with diabetes to be associated with a substantially increased risk of dementia and AD, and with structural brain changes among dementia-free elderly people. PMID:26173052

In Vivo and In Vitro Binding of Vip3Aa to Spodoptera frugiperda Midgut and Characterization of Binding Sites by 125I Radiolabeling

PubMed Central

Chakroun, Maissa

2014-01-01

Bacillus thuringiensis vegetative insecticidal proteins (Vip3A) have been recently introduced in important crops as a strategy to delay the emerging resistance to the existing Cry toxins. The mode of action of Vip3A proteins has been studied in Spodoptera frugiperda with the aim of characterizing their binding to the insect midgut. Immunofluorescence histological localization of Vip3Aa in the midgut of intoxicated larvae showed that Vip3Aa bound to the brush border membrane along the entire apical surface. The presence of fluorescence in the cytoplasm of epithelial cells seems to suggest internalization of Vip3Aa or a fragment of it. Successful radiolabeling and optimization of the binding protocol for the 125I-Vip3Aa to S. frugiperda brush border membrane vesicles (BBMV) allowed the determination of binding parameters of Vip3A proteins for the first time. Heterologous competition using Vip3Ad, Vip3Ae, and Vip3Af as competitor proteins showed that they share the same binding site with Vip3Aa. In contrast, when using Cry1Ab and Cry1Ac as competitors, no competitive binding was observed, which makes them appropriate candidates to be used in combination with Vip3A proteins in transgenic crops. PMID:25002420

Ab initio and DFT study of hydrogen bond interactions between ascorbic acid and dimethylsulfoxide based on FT-IR and FT-Raman spectra

NASA Astrophysics Data System (ADS)

Niazazari, Naser; Zatikyan, Ashkhen L.; Markarian, Shiraz A.

2013-06-01

The hydrogen bonding of 1:1 complexes formed between L-ascorbic acid (LAA) and dimethylsulfoxide (DMSO) has been studied by means of ab initio and density functional theory (DFT) calculations. Solutions of L-ascorbic acid (AA) in dimethylsulfoxide (DMSO) have been studied by means of both FT-IR (4000-220 cm-1) and FT-Raman spectroscopy. Ab initio Hartree-Fock (HF) and DFT methods have been used to determine the structure and energies of stable conformers of various types of L-AA/DMSO complexes in gas phase and solution. The basis sets 6-31++G∗∗ and 6-311+G∗ were used to describe the structure, energy, charges and vibrational frequencies of interacting complexes in the gas phase. The optimized geometric parameters and interaction energies for various complexes at different theories have been estimated. Binding energies have been corrected for basis set superposition error (BSSE) and harmonic vibrational frequencies of the structures have been calculated to obtain the stable forms of the complexes. The self-consistent reaction field (SCRF) has been used to calculate the effect of DMSO as the solvent on the geometry, energy and charges of complexes. The solvent effect has been studied using the Onsager models. It is shown that the polarity of the solvent plays an important role on the structures and relative stabilities of different complexes. The results obtained show that there is a satisfactory correlation between experimental and theoretical predictions.

Interaction between Na-K-ATPase and Bcl-2 proteins BclXL and Bak.

PubMed

Lauf, Peter K; Alqahtani, Tariq; Flues, Karin; Meller, Jaroslaw; Adragna, Norma C

2015-01-01

In silico analysis predicts interaction between Na-K-ATPase (NKA) and Bcl-2 protein canonical BH3- and BH1-like motifs, consistent with NKA inhibition by the benzo-phenanthridine alkaloid chelerythrine, a BH3 mimetic, in fetal human lens epithelial cells (FHLCs) (Lauf PK, Heiny J, Meller J, Lepera MA, Koikov L, Alter GM, Brown TL, Adragna NC. Cell Physiol Biochem 31: 257-276, 2013). This report establishes proof of concept: coimmunoprecipitation and immunocolocalization showed unequivocal and direct physical interaction between NKA and Bcl-2 proteins. Specifically, NKA antibodies (ABs) coimmunoprecipitated BclXL (B-cell lymphoma extra large) and BAK (Bcl-2 antagonist killer) proteins in FHLCs and A549 lung cancer cells. In contrast, both anti-Bcl-2 ABs failed to pull down NKA. Notably, the molecular mass of BAK1 proteins pulled down by NKA and BclXL ABs appeared to be some 4-kDa larger than found in input monomers. In silico analysis predicts these higher molecular mass BAK1 proteins as alternative splicing variants, encoding 42 amino acid (aa) larger proteins than the known 211-aa long canonical BAK1 protein. These BAK1 variants may constitute a pool separate from that forming mitochondrial pores by specifically interacting with NKA and BclXL proteins. We propose a NKA-Bcl-2 protein ternary complex supporting our hypothesis for a special sensor role of NKA in Bcl-2 protein control of cell survival and apoptosis. Copyright © 2015 the American Physiological Society.

Interactions between genetic polymorphisms of glucose metabolizing genes and smoking and alcohol consumption in the risk of type 2 diabetes mellitus.

PubMed

Gao, Kaiping; Ren, Yongcheng; Wang, Jinjin; Liu, Zichen; Li, Jianna; Li, Linlin; Wang, Bingyuan; Li, Hong; Wang, Yaxi; Cao, Yunkai; Ohno, Kinji; Zhai, Rihong; Liang, Zhen

2017-12-01

The impact of gene-environment interaction on diabetes remains largely unknown. We aimed to investigate if interaction between glucose metabolizing genes and lifestyle factors is associated with type 2 diabetes mellitus (T2DM). Interactions between genotypes of 4 glucose metabolizing genes (MTNR1B, KCNQ1, KLF14, and GCKR) and lifestyle factors were estimated in 722 T2DM patients and 759 controls, using multiple logistic regression. No significant associations with T2DM were detected for the single nucleotide polymorphisms of MTNR1B, KLF14 and GCKR. However, rs151290 (KCNQ1) polymorphisms were found to be associated with risk of T2DM. Compared with AA, the odds ratios (ORs) of AC or CC genotypes for developing T2DM were 1.545 (P = 0.0489) and 1.603 (P = 0.0383), respectively. In stratified analyses, the associations were stronger in smokers with CC than smokers with AA (OR = 3.668, P = 0.013); drinkers with AC (OR = 5.518, P = 0.036), CC (OR = 8.691, P = 0.0095), and AC+CC (OR = 6.764, P = 0.016) than drinkers with AA. Compared with nondrinkers with AA, drinkers who carry AC and CC had 12.072-fold (P = 0.0007) and 8.147-fold (P = 0.0052) higher risk of developing T2DM. In conclusions, rs151290 (KCNQ1) polymorphisms are associated with increased risk of T2DM, alone and especially in interaction with smoking and alcohol.

The association of DLG5 polymorphisms with inflammatory bowel disease: a meta-analysis of 25 studies.

PubMed

Dai, Y-E; Guan, R; Song, Y-T

2016-06-01

The aim of this study was to explore the association of polymorphisms in DLG5 gene (G113A, C4136A and e26) with inflammatory bowel disease (IBD) risk. A total of 25 studies involved 26583 subjects were pooled for analysis. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to pool the effect size. For G113A variant, a significant association was observed with CD risk in children (A vs. G: OR = 0.745, 95% CI = 0.569-0.977) and high quality studies (A vs. G: OR = 0.913, 95% CI = 0.850-0.981). Additionally, the results of genotype-phenotype analysis suggested G113A variant was associated with colonic involvement in CD. However, in overall population, the results indicated G113A variant was not associated with CD or UC. We also provided evidence that C4136A polymorphism had different effects on CD risk between Europeans (AA vs. CC: OR = 3.239, 95% CI = 1.149-9.136) and Asians (AA vs. CC: OR = 0.511, 95% CI = 0.299-0.873). For UC, patients with AA genotype of C4136A variant had a significantly increased UC risk (AA vs. CC: OR = 3.877, 95% CI = 1.168-12.867). Finally, no association was detected with G113A or e26 polymorphism in CD or UC patients. This meta-analysis indicated G113A variant may be significantly associated with CD risk in children and colonic involvement.

Interleukin-10 -1082 promoter polymorphism associated with gastric cancer among Asians.

PubMed

Zhou, Yong; Li, Ni; Zhuang, Wen; Liu, Guan-Jian; Wu, Tai-Xiang; Yao, Xun; Du, Liang; Wei, Mao-Ling; Wu, Xiao-Ting

2008-11-01

Studies investigating the association between interleukin-10 (IL-10) -1082 promoter polymorphism and gastric cancer risk report conflicting results. The objective of this study was to quantitatively summarise the evidence for such a relationship. Two investigators independently searched the Medline and Embase databases. This meta-analysis included 13 case-control studies, which included 2227 gastric cancer cases and 3538 controls. The combined results based on all studies showed that there was no significant difference in genotype distribution [AA odds ratio (OR)=0.92, 95% confidence interval (CI)=0.73, 1.14; AG (OR=1.09, 95% CI=0.87, 1.36); GG (OR=1.03, 95% CI=0.85, 1.25)] between gastric cancer and noncancer patients. When stratifying for race, results were similar except that patients with gastric cancer had a significantly lower frequency of AA (OR=0.71, 95% CI=0.52, 0.97) and higher frequency AG (OR=1.53, 95% CI=1.15, 2.03) than noncancer patients among Asians. When stratifying by the location of gastric cancer, we found that patients with cardia gastric cancer had a significantly lower frequency of AA (OR=0.53, 95% CI=0.34, 0.83) and higher frequency AG (OR=1.50, 95% CI=1.06, 2.11) than those with noncardia gastric cancer among Caucasians. When stratifying by the Lauren's classification of gastric cancer, we observed no statistically significant differences in genotype distribution. This meta-analysis suggests that the IL-10 -1082 promoter polymorphism may be associated with gastric cancer among Asians, and that differences in genotype distribution may be associated with the location of gastric cancer.

APOE Modulates the Correlation Between Triglycerides, Cholesterol, and CHD Through Pleiotropy, and Gene-by-Gene Interactions

PubMed Central

Maxwell, Taylor J.; Ballantyne, Christie M.; Cheverud, James M.; Guild, Cameron S.; Ndumele, Chiadi E.; Boerwinkle, Eric

2013-01-01

Relationship loci (rQTL) exist when the correlation between multiple traits varies by genotype. rQTL often occur due to gene-by-gene (G × G) or gene-by-environmental interactions, making them a powerful tool for detecting G × G. Here we present an empirical analysis of apolipoprotein E (APOE) with respect to lipid traits and incident CHD leading to the discovery of loci that interact with APOE to affect these traits. We found that the relationship between total cholesterol (TC) and triglycerides (ln TG) varies by APOE isoform genotype in African-American (AA) and European-American (EA) populations. The e2 allele is associated with strong correlation between ln TG and TC while the e4 allele leads to little or no correlation. This led to a priori hypotheses that APOE genotypes affect the relationship of TC and/or ln TG with incident CHD. We found that APOE*TC was significant (P = 0.016) for AA but not EA while APOE*ln TG was significant for EA (P = 0.027) but not AA. In both cases, e2e2 and e2e3 had strong relationships between TC and ln TG with CHD while e2e4 and e4e4 results in little or no relationship between TC and ln TG with CHD. Using ARIC GWAS data, scans for loci that significantly interact with APOE produced four loci for African Americans (one CHD, one TC, and two HDL). These interactions contribute to the rQTL pattern. rQTL are a powerful tool to identify loci that modify the relationship between risk factors and disease and substantially increase statistical power for detecting G × G. PMID:24097412

Single-Nucleotide Polymorphisms of FAS and FASL Genes and Risk of Idiopathic Aplastic Anemia.

PubMed

Rehman, Sadia; Saba, Nusrat; Naz, Madiha; Ahmed, Parvez; Munir, Saeeda; Sajjad, Sumaira; Tabassum, Sobia; Naseem, Lubna

2018-04-03

FAS/FASL signaling system plays a vital role in the regulation of apoptosis, envisaged as a death process required for immune surveillance to prevent autoimmunity and tumorigenesis along with several other biological activities. Several single-nucleotide polymorphisms (SNPs) of FAS/FASL system can result in aberrant apoptosis, which can cause different cancers and autoimmune diseases. Aplastic anemia (AA) is an autoimmune dysfunction characterized by peripheral blood pancytopenia associated with hypoplasia of bone marrow. The aim of this study was to screen Pakistani AA patients and controls for two Fas SNPs rs2234767 and rs1800682 and two FASLG SNPs rs763110 and rs5030772. Genotyping of 392 DNA samples was done by Tetra-ARMS polymerase chain reaction. Genotypic frequencies of Fas rs1800682 and FASLG rs5030772 showed significance difference in their distribution in both controls and patients, while Fas rs2234767 and FASLG rs763110 SNPs had no such difference. Carriers of rs1800682 AG+GG had a very odd ratio of 4.63, with 95% confidence interval (CI) of 3.01-7.11, while individuals with FASLG rs5030772 AG+GG were more common in controls than patients with OR 0.53 and 95% CI of 0.34-0.83. Cumulative effects of these SNPs were analyzed, and they showed almost similar trends; however, Fas rs2234767 and FASLG rs763110 genotypes in combination with Fas rs1800682 and FASLG rs5030772 demonstrated significant association. This study provided information that endorsed the involvement of FAS/FASL system SNPs in the pathogenesis of AA; further studies should be designed to understand the exact role of SNPs that can help in early diagnosis and treatment.

Association of PCK1 with Body Mass Index and Other Metabolic Features in Patients With Psychotropic Treatments.

PubMed

Saigi-Morgui, Núria; Vandenberghe, Frederik; Delacrétaz, Aurélie; Quteineh, Lina; Choong, Eva; Gholamrezaee, Mehdi; Magistretti, Pierre; Aubry, Jean-Michel; von Gunten, Armin; Preisig, Martin; Castelao, Enrique; Vollenweider, Peter; Waeber, Gerard; Kutalik, Zoltán; Conus, Philippe; Eap, Chin B

2015-10-01

Weight gain is a major health problem among psychiatric populations. It implicates several receptors and hormones involved in energy balance and metabolism. Phosphoenolpyruvate carboxykinase 1 is a rate-controlling enzyme involved in gluconeogenesis, glyceroneogenesis and cataplerosis and has been related to obesity and diabetes phenotypes in animals and humans. The aim of this study was to investigate the association of phosphoenolpyruvate carboxykinase 1 polymorphisms with metabolic traits in psychiatric patients treated with psychotropic drugs inducing weight gain and in general population samples. One polymorphism (rs11552145G > A) significantly associated with body mass index in the psychiatric discovery sample (n = 478) was replicated in 2 other psychiatric samples (n1 = 168, n2 = 188), with AA-genotype carriers having lower body mass index as compared to G-allele carriers. Stronger associations were found among women younger than 45 years carrying AA-genotype as compared to G-allele carriers (-2.25 kg/m, n = 151, P = 0.009) and in the discovery sample (-2.20 kg/m, n = 423, P = 0.0004). In the discovery sample for which metabolic parameters were available, AA-genotype showed lower waist circumference (-6.86 cm, P = 0.008) and triglycerides levels (-5.58 mg/100 mL, P < 0.002) when compared to G-allele carriers. Finally, waist-to-hip ratio was associated with rs6070157 (proxy of rs11552145, r = 0.99) in a population-based sample (N = 123,865, P = 0.022). Our results suggest an association of rs11552145G > A polymorphism with metabolic-related traits, especially in psychiatric populations and in women younger than 45 years.

Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure.

PubMed

Speakman, John R; Rance, Kellie A; Johnstone, Alexandra M

2008-08-01

The FTO gene has significant polymorphic variation associated with obesity, but its function is unknown. We screened a population of 150 whites (103F/47M) resident in NE Scotland, United Kingdom, for variants of the FTO gene and linked these to phenotypic variation in their energy expenditure (basal metabolic rate (BMR) and maximal oxygen consumption VO(2)max) and energy intake. There was no significant association between the FTO genotype and BMR or VO(2)max. The FTO genotype was significantly associated (P = 0.024) with variation in energy intake, with average daily intake being 9.0 MJ for the wild-type TT genotype and 10.2 and 9.5 MJ for the "at risk" AT and AA genotypes, respectively. Adjusting intake for BMR did not remove the significance (P = 0.043). FTO genotype probably affects obesity via effects on food intake rather than energy expenditure.

Vitamin-D receptor (VDR) gene polymorphisms (Taq-I & Apa-I) in Syrian healthy population.

PubMed

Haddad, Shaden

2014-12-01

The vitamin D endocrine system regulates bone metabolism and calcium homeostasis as well as cellular proliferation and differentiation. Vitamin D receptor (VDR) mediates Vit-D activity, thus VDR gene polymorphisms may correlate with different diseases. This study aimed to determine the distribution of VDR gene (Taq-I and Apa-I) polymorphisms using a RFLP in unrelated normal healthy individuals of Syrian population. Allelic frequencies were 65% vs 35% and 66% vs 34% for T vs t and A vs a alleles, respectively. Genotype distribution was 36%, 58% and 6% for TT, Tt and tt and 42%, 47% and 10% for AA, Aa and aa, respectively. These results demonstrate that the frequency and distribution of the VDR polymorphisms in Syrian population are different from other populations worldwide.

Genotyping of occult hepatitis B virus infection in Egyptian hemodialysis patients without hepatitis C virus infection.

PubMed

Esmail, Mona A; Mahdi, Wafaa K M; Khairy, Rasha M; Abdalla, Nilly H

2016-01-01

Occult hepatitis B viral infection is the presence of hepatitis B viral nucleic acids in the serum and/or liver in the absence of hepatitis B surface antigen. The study aimed to determine the prevalence of occult hepatitis B virus infection among hepatitis C virus-negative hemodialysis patients and to identify their genotypes. of 144 patients on maintenance hemodialysis, 50 hepatitis B surface antigen and hepatitis C virus nucleic acid-negative patients were selected according to strict inclusion criteria to avoid the effect of confounding variables. The following investigations were done: serum AST and ALT; HBsAg; HBcAb; HCV-Ab; HCV-RNA; and HBV-DNA. Positive hepatitis B viral nucleic acid was confirmed in 12/144 (8.3%) hemodialysis patients and 12/50 (24%) in our study group (occult infection). Mean hemodialysis periods for negative patients and occult hepatitis B virus patients were 27.3±18.8 and 38.4±8.14 months, respectively, and this difference was significant (p-value=0.02). Mean alanine transaminase levels were 20.27±5.5IU/L and 25.3±9.6 in negative patients and occult infection patients, respectively. This difference was non-significant. Aspartate transaminase levels were 21.4±10.2IU/L and 27.3±4.6IU/L, respectively, in negative patients and infected patients; this difference was significant (p-value=0.03). Half (6/12) of the positive samples belonged to genotype 'B', 33.3% (4/12) to 'C', and 16.6% (2/12) to genotype 'D'. OBI is likely among hemodialysis patients even without HCV coinfection (24%). Genotype D cannot be the only genotype distributed in Upper Egypt, as the current study reported relatively new results that 50% of the patients with occult B carry genotype B, 33.3% carry genotype C and only 16.6% carry genotype D. Copyright © 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Correlation between methyltetrahydrofolate reductase (MTHFR) polymorphisms and isolated patent ductus arteriosus in Taiwan.

PubMed

Chao, Chia-Sheng; Wei, Jeng; Huang, Hurng-Wern; Yang, Shyh-Chyun

2014-07-01

Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C gene polymorphisms are associated with the risk of patent ductus arteriosus (PDA) congenital heart defects. This study aimed to determine the association of these polymorphisms in patients with isolated PDA and in non-PDA patients group without congenital heart disease. This retrospective case-controlled study was undertaken in 17 patients with isolated PDA and a control non-PDA group consisting of 34 subjects without congenital heart disease. MTHFR gene polymorphisms were analysed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In addition, the genotype distribution of the MTHFR gene was compared among different ethnicities using the HapMap database. In contrast to the MTHFR C677T polymorphism, differences in the MTHFR A1298C genotype were observed between the two groups (P=0.002); a greater proportion of the PDA patients had the MTHFR 1298CC and 1298AA genotypes as compared to the non-PDA control group. After merging the data obtained from the Taiwanese participants with that from the HapMap database, genetic diversity of the MTHFR 1298AA genotype was observed. Thus, the MTHFR A1298C polymorphism is associated with isolated PDA in Taiwan. Larger studies are necessary to evaluate the prognostic value of determining MTHFR polymorphism in PDA. Copyright © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Polymorphisms of Glutathione S-transferases Omega-1 among ethnic populations in China

PubMed Central

Fu, Songbo; Wu, Jie; Chen, Feng; Sun, Dianjun; Fu, Songbin

2008-01-01

Background Glutathione S-transferases (GSTs) is a genetic factor for many diseases and exhibits great diversities among various populations. We assessed association of the genotypes of Glutathione S-transferases Omega-1 (GSTO1) A140D with ethnicity in China. Results Peripheral blood samples were obtained from 1314 individuals from 14 ethnic groups. Polymorphisms of GSTO1 A140D were measured using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Logistic regression was employed to adjustment for regional factor. The frequency of GSTO1 140A allele was 15.49% in the total 14 ethnic populations. Compared to Han ethnic group, two ethnic populations were more likely to have AA or CA genotype [odds ratio (OR): 1.77, 95% confidence interval (95% CI): 1.05–2.98 for Uygur and OR: 1.78, 95% CI: 1.18–2.69 for Hui]. However, there were no statistically significant differences across 14 ethnic groups when region factor was adjusted. In Han ethnicity, region was significantly associated with AA or CA genotype. Han individuals who resided in North-west of China were more likely to have these genotypes than those in South of China (OR: 1.63, 95% CI: 1.21–2.20). Conclusion The prevalence of the GSTO1 140A varied significantly among different regional populations in China, which showed that geography played a more important role in the population differentiation for this allele than the ethnicity/race. PMID:18400112

CK-MM and ACE genotypes and physiological prediction of the creatine kinase response to exercise.

PubMed

Heled, Yuval; Bloom, Michael S; Wu, T John; Stephens, Quiona; Deuster, Patricia A

2007-08-01

Exertional rhabdomyolysis (ERB) is a syndrome of severe skeletal muscle breakdown. Blood levels of creatine kinase (CK) are widely used as a marker to reflect muscle breakdown. Some individuals exhibit extreme increases in blood CK after exercise and have been characterized as high responders (HR), but no clinical definition of HR exists and reasons for the HR phenomenon are not understood. This study investigated possible associations between the magnitude of the CK response to exercise and polymorphisms of two genes: muscle-specific creatine kinase (CK-MM) NcoI and angiotensin-converting enzyme (ACE) I/D. An exercise test for defining HR was also investigated. Participants (n = 88) underwent an exercise test that included stepping up and down two stairs for 5 min followed by 15 squats while wearing a backpack weighted at 30% of their body weight. CK levels were measured before, immediately after, and 48 and 72 h after the test. Nine participants (10.2%) were defined as HR. Participants with the CK-MM NcoI AA genotype had a sixfold higher risk of being HR compared with GG and AG genotypes (P = 0.031). No significant differences were found for the ACE I/D polymorphism. Percent body fat was an independent predictor of being a HR. We conclude that the CK-MM AA genotype and percent body fat may be part of the constellation of mechanisms that explain susceptibility to ERB. A physiological test that may assist in predicting ERB is also presented.

Smoking attenuated the association between IκBα rs696 polymorphism and defective spermatogenesis in humans.

PubMed

Yu, B; Ding, Q; Zheng, T; Jiang, L; Li, Q; Sun, X; Bai, C; Huang, Z

2015-11-01

Defective spermatogenesis is prevalent in infertile men, but the molecular mechanisms underlying its aetiology are largely unknown. In this study, a proposed association between IκBα SNPs, smoking-related ROS and sperm quality was investigated. Two polymorphisms in the IκBα gene, rs2233406 and rs696 were genotyped in 342 controls and 338 patients with defective spermatogenesis from a southern Chinese population. The results showed the rs696 AA genotype to be significantly more common (21.60% versus 14.33%, P = 0.013) and the rs696 GG genotype to be significantly rarer (28.99% versus 37.13%, P = 0.024) in the cases than in the controls. After subjects were stratified into smokers and nonsmokers, these differences were only observed in nonsmokers. Further analysis showed the rs696 AA genotype to be significantly closely associated with defective spermatogenesis in all subjects (P = 0.014, OR = 1.647) and in nonsmokers (P = 0.036, OR = 1.889). In a TM3 cell model, exposure to cigarette smoke condensate was found to activate NF-κB luciferase activity and altered transcriptional level of NF-κB pathway genes. In conclusion, this study demonstrates an association between functional polymorphisms of the IκBα rs696 and cigarette smoking with the risk of defective spermatogenesis, suggesting some interaction between the NF-κB signalling pathway and smoking-related ROS in human spermatogenesis. © 2014 Blackwell Verlag GmbH.

Characterization of monoclonal antibodies that specifically recognize the palm subdomain of hepatitis C virus nonstructural protein 5B polymerase.

PubMed

Ingravallo, P; Lahser, F; Xia, E; Sodowich, B; Lai, V C; Hong, Z; Zhong, W

2001-06-01

The nonstructural protein 5B (NS5B) of hepatitis C virus (HCV) is an RNA-dependent RNA polymerase (RdRp) which plays an essential role in viral RNA replication. Antibodies that specifically recognize NS5B will have utilities in monitoring NS5B production and subcellular localization, as well as in structure-function studies. In this report, three mouse monoclonal antibodies (mAbs), 16A9C9, 16D9A4 and 20A12C7, against a recombinant NS5B protein (genotype 1a, H-77 strain) were produced. These mAbs specifically recognize HCV NS5B, but not RdRps of polivirus (PV), bovine viral diarrhea virus (BVDV) or GB virus B (GBV-B). The mAbs can readily detect NS5B in cellular lysates of human osteosarcoma Saos2 cells constitutively expressing the nonstructural region of HCV (NS3-NS4A-NS4B-NS5A-NS5B). NS5B proteins of different HCV genotypes/subtypes (1a, 1b, 2a, 2c, 5a) showed varied affinity for these mAbs. Interestingly, the epitopes for the mAbs were mapped to the palm subdomain (amino acid 188-370) of the HCV RdRp as determined by immunoblotting analysis of a panel of HCV/GBV-B chimeric NS5B proteins. The binding site was mapped between amino acid 231 and 267 of NS5B for 16A9C9, and between 282 and 372 for 16D9A4 and 20A12C7. Furthermore, these mAbs showed no inhibitory effect on the NS5B polymerase activity in vitro.

Isolation of midgut escape mutants of two American genotype dengue 2 viruses from Aedes aegypti

PubMed Central

2013-01-01

Background Several studies have shown that American genotype dengue 2 viruses (DENV2) have reduced viral fitness in the mosquito vector, Aedes aegypti, compared to other DENV2 genotypes. Diminished replication efficiency or inability to efficiently traverse membrane barriers encompassing organs such as the midgut or salivary glands are considered major factors negatively impacting viral fitness in the mosquito. Results We analyzed the vector competence of Ae. aegypti for two American DENV2 strains, QR94 and PR159 originating from Mexico and Puerto-Rico, respectively. Both strains infected mosquito midguts following acquisition of infectious bloodmeals. However, DENV2-QR94 and DENV2-PR159 poorly disseminated from the midgut at 7 or 14 days post-bloodmeal (pbm). We detected one virus isolate, EM33, among 31 DENV2-QR94 infected mosquitoes, and one isolate, EM41, among 121 DENV2-PR159 infected mosquitoes, generating high virus titers in mosquito carcasses at 7 days pbm. In oral challenge experiments, EM33 and EM41 showed midgut dissemination rates of 40-50%. Replication efficiency of EM41 in secondary mosquito tissue was similar to that of a dissemination-competent control strain, whereas the replication efficiency of EM33 was significantly lower than that of the control virus. The genome sequence of DENV2-QR94 encoded seven unique amino acids (aa), which were not found in 100 of the most closely related DENV2 strains. EM33 had one additional aa change, E202K, in the E protein. DENV2-PR159 encoded four unique aa residues, one of them E202K, whereas EM41 had two additional aa substitutions, Q77E in the E protein and E93D in NS3. Conclusions Our results indicate that the midgut of Ae. aegypti acts as a selective sieve for DENV2 in which genetically distinct, dissemination-competent virus variants are rapidly selected from the viral quasispecies to be transmitted to vertebrates. PMID:23937713

Genetic variation in FADS genes is associated with maternal long-chain PUFA status but not with cognitive development of infants in a high fish-eating observational study.

PubMed

Yeates, Alison J; Love, Tanzy M; Engström, Karin; Mulhern, Maria S; McSorley, Emeir M; Grzesik, Katherine; Alhamdow, Ayman; Wahlberg, Karin; Thurston, Sally W; Davidson, Philip W; van Wijngaarden, Edwin; Watson, Gene E; Shamlaye, Conrad F; Myers, G J; Strain, J J; Broberg, Karin

2015-12-01

Long-chain n-6 and n-3 PUFA (LC-PUFA), arachidonic acid (AA) (20:4n-6) and DHA (22:6n-3), are critical for optimal brain development. These fatty acids can be consumed directly from the diet, or synthesized endogenously from precursor PUFA by Δ-5 (encoded by FADS1) and Δ-6 desaturases (encoded by FADS2). The aim of this study was to determine the potential importance of maternal genetic variability in FADS1 and FADS2 genes to maternal LC-PUFA status and infant neurodevelopment in populations with high fish intakes. The Nutrition Cohorts 1 (NC1) and 2 (NC2) are longitudinal observational mother-child cohorts in the Republic of Seychelles. Maternal serum LC-PUFA was measured at 28 weeks gestation and genotyping for rs174537 (FADS1), rs174561 (FADS1), rs3834458 (FADS1-FADS2) and rs174575 (FADS2) was performed in both cohorts. The children completed the Bayley Scales of Infant Development II (BSID-II) at 30 months in NC1 and at 20 months in NC2. Complete data were available for 221 and 1310 mothers from NC1 and NC2 respectively. With increasing number of rs3834458 minor alleles, maternal concentrations of AA were significantly decreased (NC1 p=0.004; NC2 p<0.001) and precursor:product ratios for linoleic acid (LA) (18:2n-6)-to-AA (NC1 p<0.001; NC2 p<0.001) and α-linolenic acid (ALA) (18:3n-3)-to-DHA were increased (NC2 p=0.028). There were no significant associations between maternal FADS genotype and BSID-II scores in either cohort. A trend for improved PDI was found among infants born to mothers with the minor rs3834458 allele.In these high fish-eating cohorts, genetic variability in FADS genes was associated with maternal AA status measured in serum and a subtle association of the FADS genotype was found with neurodevelopment. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Case-control study of eczema associated with IL13 genetic polymorphisms in Japanese children.

PubMed

Miyake, Yoshihiro; Kiyohara, Chikako; Koyanagi, Midori; Fujimoto, Takahiro; Shirasawa, Senji; Tanaka, Keiko; Sasaki, Satoshi; Hirota, Yoshio

2011-01-01

Several association studies have investigated the relationships between single nucleotide polymorphisms (SNPs) in the IL13 gene and eczema, with inconsistent results. We conducted a case-control study of the relationship between the polymorphisms of rs1800925 and rs20541 and the risk of eczema in Japanese children aged 3 years. Included were the 209 cases identified based on criteria of the International Study of Asthma and Allergies in Childhood (ISAAC). Controls were 451 children without eczema based on ISAAC questions who had not been diagnosed by a physician as having asthma or atopic eczema. The minor TT genotype of the rs1800925 SNP and the minor AA genotype of the rs20541 SNP were significantly related to an increased risk of eczema: adjusted odds ratio for the TT genotype was 2.78 (95% confidence interval 1.22-6.30) and that for the AA genotype was 2.38 (95% confidence interval 1.35-4.18). Haplotype analyses showed a protective association between the CG haplotype and eczema, whereas the TA haplotype was positively related to the risk of eczema. Perinatal smoking exposure did not interact with genotypes of the IL13 gene in the etiology of eczema. The significant association of the rs20541 SNP with eczema essentially disappeared after additional adjustment for the rs1800925 SNP, whereas a relationship with the rs1800925 SNP remained significant. A common genetic variation in the IL13 gene at the levels of both single SNPs and haplotypes was associated with eczema. However, the significant association with the rs20541 SNP might be ascribed to the rs1800925 SNP. Copyright © 2010 S. Karger AG, Basel.

Inverse correlation between HPSE gene single nucleotide polymorphisms and heparanase expression: possibility of multiple levels of heparanase regulation

PubMed Central

Ostrovsky, Olga; Korostishevsky, Michael; Shafat, Itay; Mayorov, Margarita; Ilan, Neta; Vlodavsky, Israel; Nagler, Arnon

2009-01-01

Heparanase is an endo-β-glucuronidase that specifically cleaves the saccharide chains of heparan sulfate proteoglycans. Heparanase plays important roles in processes such as angiogenesis, tumor metastasis, tissue repair and remodeling, inflammation and autoimmunity. Genetic variations of the heparanase gene (HPSE) have been associated with heparanase transcription level. The present study was undertaken to identify haplotype or single nucleotide polymorphisms (SNPs) genotype combinations that correlate with heparanase expression both at the mRNA and protein levels. For this purpose, 11 HPSE gene SNPs were genotyped among 108 healthy individuals. Five out of the eleven polymorphisms revealed an association between the SNPs and heparanase expression. SNP rs4693608 exhibited a strong evidence of association. Analysis of haplotypes distribution revealed that the combination of two SNPs (rs4693608 and rs4364254) disclosed the most significant result. This approach allowed segregation of possible genotype combinations to three groups that correlate with low (LR: GG-CC, GG-CT, GG-TT, GA-CC), intermediate (MR: GA-CT, GA-TT) and high (HR: AA-TT, AA-CT) heparanase expression. Unexpectedly, LR genotype combinations were associated with low mRNA expressions level and high heparanase concentration in plasma, while HR genotype combinations were associated with high expression of mRNA and low plasma protein level. Because the main site of activity of secreted active heparanase is the extracellular matrix and cell surface, the origin and functional significance of plasma heparanase remain to be investigated. The current study indicates that rs4693608 and rs4364254 SNPs are involved in the regulation of heparanase expression and provides the basis for further studies on the association between HPSE gene SNPs and disease outcome. PMID:19406828

A genome-wide association and gene-environment interaction study for serum triglycerides levels in a healthy Chinese male population.

PubMed

Tan, Aihua; Sun, Jielin; Xia, Ning; Qin, Xue; Hu, Yanling; Zhang, Shijun; Tao, Sha; Gao, Yong; Yang, Xiaobo; Zhang, Haiying; Kim, Seong-Tae; Peng, Tao; Lin, Xiaoling; Li, Li; Mo, Linjian; Liang, Zhengjia; Shi, Deyi; Huang, Zhang; Huang, Xianghua; Liu, Ming; Ding, Qiang; Trent, Jeffrey M; Zheng, S Lilly; Mo, Zengnan; Xu, Jianfeng

2012-04-01

Triglyceride (TG) is a complex phenotype influenced by both genetic and environmental factors. Recent genome-wide association studies (GWAS) have identified genes or loci affecting lipid levels; however, such studies in Chinese populations are limited. A two-stage GWAS were conducted to identify genetic variants that were associated with TG in a Chinese population of 3495 men. Gene-environment interactions on serum TG levels were further investigated for the seven single nucleotide polymorphisms (SNPs) that were studied in both stages. Two previously reported SNPs (rs651821 in APOA5, rs328 in LPL) were replicated in the second stage, and the combined P-values were 9.19 × 10(-26) and 1.41 × 10(-9) for rs651821 and rs328, respectively. More importantly, a significant interaction between aldehyde dehydrogenase 2 (ALDH2) rs671 and alcohol consumption on serum TG levels were observed (P = 3.34 × 10(-5)). Rs671 was significantly associated with serum TG levels in drinkers (P = 1.90 × 10(-10)), while no association was observed in non-drinkers (P > 0.05). For drinkers, men carrying the AA/AG genotype have significantly lower serum TG levels, compared with men carrying the GG genotype. For men with the GG genotype, the serum TG levels increased with the quantity of alcohol intake (P = 1.28 × 10(-8) for trend test). We identified a novel, significant interaction effect between alcohol consumption and the ALDH2 rs671 polymorphism on TG levels, which suggests that the effect of alcohol intake on TG occurs in a two-faceted manner. Just one drink can increase TG level in susceptible individuals who carry the GG genotype, while individuals carrying AA/AG genotypes may actually benefit from moderate drinking.

Associations of MMP1, MMP2 and MMP3 Genes Polymorphism with Coal Workers’ Pneumoconiosis in Chinese Han Population

PubMed Central

Ji, Xiaoming; Wang, Lijuan; Wu, Baiqun; Han, Ruhui; Han, Lei; Wang, Ting; Yang, Jingjin; Ni, Chunhui

2015-01-01

Coal workers’ pneumoconiosis (CWP) has been associated with abnormalities in the extracellular matrix remodeling, as well as aberrant matrix metalloproteinases (MMPs) in lung tissues. We investigated the association of three functional polymorphisms in MMP gene promoters (MMP1 rs1799750, MMP2 rs2285053 and MMP3 rs522616) with the risk of CWP. A total of 693 CWP cases and 690 controls were included in a case-control study. Genotype analysis was performed by the TaqMan method. Statistically significant differences were found in distributions of MMP3 rs522616 under a recessive model (p = 0.047) between CWP cases and controls. In the stratification analysis, individuals with MMP3 rs522616 GG genotype decreased the risk of CWP (adjusted OR = 0.72, 95% CI = 0.52–0.99) compared to those with AA/AG genotype obviously, particularly among subgroups of no smokers (adjusted OR = 0.64, 95% CI = 0.41–1.00). Furthermore, serum MMP3 protein levels measured with enzyme-linked immune-sorbent assay in the control group was significantly lower than that in the CWP groups (p = 0.02). Extremely lower MMP3 among subjects with the rs522616 GG or AG genotype compared with the AA genotype carriers (p < 0.05, p < 0.01 respectively) in the normal serum. These findings indicate that the MMP3 rs522616 polymorphism may contribute to the etiology of CWP in the Chinese population and MMP3 might be a potential diagnostic biomarker for CWP, additional independent studies are warranted to validate our findings in different populations as well as in a larger series. PMID:26528997

Associations of ICOS and PD.1 Gene Variants with Colon Cancer Risk in The Iranian Population

PubMed

Shamsdin, Seyedeh Azra; Karimi, Mohammad Hossein; Hosseini, Seyed Vahid; Geramizadeh, Bita; Fattahi, Mohamad Reza; Mehrabani, Davood; Moravej, Ali

2018-03-27

Background: Positive and negative co-stimulatory molecules are important factors determining the outcome of immune responses to the presence of tumors. Since co-stimulatory molecule expression may be affected by gene polymorphisms, we aimed to investigate associations between variants of PD.1 and ICOS and susceptibility to colon cancer. Material and methods: ICOS (-693A/G), ICOS (+1720C/T) and PD.1 (-538G/A) gene polymorphisms were evaluated by the PCR-RFLP method in 76 colon cancer patients and 73 healthy controls. Results: The frequencies of the GG genotype and the G allele at position -693 of the ICOS gene were significantly higher in the patient group (P=0.014 and p=0.0002), while the AA genotype was significantly more common in controls (P=0.0016). At position -538 of PD.1, GG genotype and G allele frequencies were higher in the patient group (P<0.0001and P<0.0001). Again, AA and also AG genotypes significantly predominated in controls (P<0.0001 and P=0.012). Regarding genotypes and alleles of ICOS at position +1720. Frequencies of GCG and GTG haplotypes were higher in patients compared to those of controls (P=0.016 and P<0.0001), while, frequencies of GTA, ATA and ATG haplotypes were higher in controls (P=0.0017, P<0.0001 and P=0.015). GTG/GTG and GTG/GCG double haplotypes were more frequent in patients compared to controls (P=0.0147 and P=0.0071). Conclusion: Our study clarified that PD.1 (-538G/A) and ICOS (-693A/G) gene polymorphisms can be considered as genetic risk factors for the development of colon cancer among Iranian patients. Creative Commons Attribution License

Frequency of rs731236 (Taql), rs2228570 (Fok1) of Vitamin-D Receptor (VDR) gene in Emirati healthy population

PubMed Central

Osman, Enas; Al Anouti, Fatme; El ghazali, Gehad; Haq, Afrozul; Mirgani, Rajaa; Al Safar, Habiba

2015-01-01

Vitamin D is getting more attention everyday due to its importance in maintaining bone and calcium homeostasis, cellular proliferation, differentiation and immune response. Vitamin D is derived from diet or elicited in the skin by the activation of 7-dehydrocholesterol, which is an inert molecule that must be activated by ultraviolet light to form pre-vitamin D3. Recent studies connected the gene encoding for vitamin D (VDR) to the genetic control of bone mass and other diseases. As VDR SNPs have been associated with several disorders and diseases, it's important to investigate the allelic and genotypic distribution among populations. The aim of this study is to determine the frequency of rs731236 (Taq1) and rs2228570 (Fok1) variants in healthy Emirati individuals and compare their genotype and allele distribution with other populations. In this study 282 (female, 187; male, 95) unrelated healthy UAE nationals were involved. Two hundreds and eight two DNA samples been collected to genotype rs731236 (Taq1) and rs2228570 (Fok1) VDR SNPs. Our results indicate that the distribution of the alleles and genotypes of rs731236 (Taq1) and rs2228570 (Fok1) vary considerably in different populations. In the Emirati population the distribution of rs731236 (Taq1) and rs2228570 (Fok1) were AA 38%, AG 42%, GG 20% and AA 27%, AG 42%, GG 31% respectively. The Emirati population genotype and allele distribution of rs731236 (Taq1) and rs2228570 (Fok1) had no difference with Caucasians from USA and France. However, there was significant difference with Asian populations. PMID:26504744

Novel SNPs of WNK1 and AKR1C3 are associated with preeclampsia.

PubMed

Sun, Cheng-Juan; Li, Lin; Li, Xueyan; Zhang, Wei-Yuan; Liu, Xiao-Wei

2018-08-20

Preeclampsia is a hypertensive disorder of pregnancy and is one of the most common causes of poor perinatal outcomes. Preeclampsia increases the risk of hypertension in the future. Variants of WNK1 (lysine deficient protein kinase 1), ADRB2 (β2 adrenergic receptor), NEDD4L (ubiquitin-protein ligase NEDD4-like), KLK1 (kallikrein 1) contribute to hypertension, and AKR1C3 (aldo-keto reductase family1 member C3), is associated with preeclampsia. The association of single nucleotide polymorphisms (SNPs) in these five candidate preeclampsia susceptibility genes and the related traits in Chinese individuals were investigated. In this study, 13 SNPs of the five genes were genotyped in 276 preeclampsia patients and 229 age- and area-matched normal pregnancies in women of Chinese Northern Han origin. The 95% confidence interval (CI) and odds ratio (OR) were estimated by binary logistic regression. No obvious linkage disequilibrium or haplotypes were observed among these SNPs. Those with GG genotype and allele G of AKR1C3 (rs10508293) had a decreased risk of preeclampsia (adjusted OR = 3.011, 95% CI = 1.758-5.159, and adjusted OR = 1.745, 95% CI = 1.349-2.257, respectively). The AA genotype and allele A of WNK1 (rs1468326) were significantly associated with an increased risk in preeclampsia (adjusted OR = 2.307, 95% CI = 1.206-3.443, and adjusted OR = 1.663, 95% CI = 1.283-2.157, respectively). The findings indicate that the GG genotype of AKR1C3 rs10508293 is associated with decreased risk for preeclampsia and the AA genotype of WNK1 rs1468326 are related with an increased risk for preeclampsia. Copyright © 2018 Elsevier B.V. All rights reserved.