Variability of chloroplast DNA and nuclear ribosomal DNA in cassava (Manihot esculenta Crantz) and its wild relatives.

PubMed

Fregene, M A; Vargas, J; Ikea, J; Angel, F; Tohme, J; Asiedu, R A; Akoroda, M O; Roca, W M

1994-11-01

Chloroplast DNA (cp) and nuclear ribosomal DNA (rDNA) variation was investigated in 45 accessions of cultivated and wild Manihot species. Ten independent mutations, 8 point mutations and 2 length mutations were identified, using eight restriction enzymes and 12 heterologous cpDNA probes from mungbean. Restriction fragment length polymorphism analysis defined nine distinct chloroplast types, three of which were found among the cultivated accessions and six among the wild species. Cladistic analysis of the cpDNA data using parsimony yielded a hypothetical phylogeny of lineages among the cpDNAs of cassava and its wild relatives that is congruent with morphological evolutionary differentiation in the genus. The results of our survey of cpDNA, together with rDNA restriction site change at the intergenic spacer region and rDNA repeat unit length variation (using rDNA cloned fragments from taro as probe), suggest that cassava might have arisen from the domestication of wild tuberous accessions of some Manihot species, followed by intensive selection. M. esculenta subspp flabellifolia is probably a wild progenitor. Introgressive hybridization with wild forms and pressures to adapt to the widely varying climates and topography in which cassava is found might have enhanced the crop's present day variability.

 Resistance-associated polymorphisms in Dutch hepatitis C genotype 1a patients with and without HIV infection.

PubMed

Lieveld, Faydra I; Swaans, Niels; Newsum, Astrid M; Ho, Cynthia K Y; Schinkel, Janke; Molenkamp, Richard; van der Meer, Jan T M; Arends, Joop E; Hoepelman, Andy I M; Wensing, Anne M J; Siersema, Peter D; van Erpecum, Karel J; Boland, Greet J

2016-01-01

 Background and aim. Resistance-associated variants (RAVs) on the NS3 region of the hepatitis C virus (HCV) may be relevant for antiviral therapy, but data in human immunodeficiency virus (HIV) coinfected patients are scarce. We assessed frequencies of NS3 RAVs in patients infected with HCV genotype 1a with or without HIV coinfection. HCV NS3 amino acids 1-181 were sequenced by the Sanger method and analyzed for RAVs. RAVs and their distribution between HCV genotype 1a clade I and II viruses were compared between HIV-infected versus HIV-uninfected patients. 148 samples were available (n = 68 HIV and n = 80 non-HIV). Relative frequency of clade I and clade II was significantly different between HIV (85% and 15%) and non-HIV groups (49% and 51%). Overall, HIV infected patients exhibited significantly lower prevalence of RAVs than HIV-uninfected patients (62% vs. 79%, p = 0.03). However, Q80K prevalence was significantly higher in HIV-infected subjects (50% vs. 24%, p = 0.001), whereas prevalence of S122D/G/N/S (2% vs. 16%, p = 0.002) and N174G/N/S (10% vs. 55%, p < 0.0001) polymorphisms were significantly lower. Q80K was found exclusively in clade I viruses. S122 (3% vs. 22%, p=0.001) and N174 (13% vs. 75%, p<0.0001) polymorphisms had significantly lower prevalence in clade I than clade II viruses. In the Netherlands, prevalence of clade I viruses and Q80K was significantly higher in HCV genotype 1a infected patients with HIV coinfection than in those without HIV coinfection. Prevalence of N174 and S122 polymorphisms was significantly higher in clade II than clade I viruses.

Prospects for genomic selection in cassava breeding

USDA-ARS?s Scientific Manuscript database

Cassava (Manihot esculenta Crantz) is a clonally propagated staple food crop in the tropics. Genomic selection (GS) has been implemented at three breeding institutions in Africa in order to reduce cycle times. Initial studies provided promising estimates of predictive abilities. Here, we expand on p...

Prevalence of multiple sclerosis in Verona, Italy: an epidemiological and genetic study.

PubMed

Gajofatto, A; Stefani, A; Turatti, M; Bianchi, M R; Lira, M G; Moretto, G; Salviati, A; Benedetti, M D

2013-04-01

Recent multiple sclerosis (MS) prevalence studies classify Italy as a high-risk area without intra-regional latitude effect. To determine MS prevalence in Verona, Italy, and frequency of myelin oligodendrocyte glycoprotein (MOG) gene G511C polymorphism and HLA-DRB1*15 locus in a sample of cases and healthy controls. The study area population on the prevalence date (31 December 2001) was 253208 (133508 women, 119700 men). Multiple case sources were examined. Patients fulfilling McDonald's criteria (2001) were included. Crude, age- and sex-specific prevalence rates were computed. MOG G511C polymorphism and HLA-DRB1*15 were determined by standard methods. We identified 270 cases of MS yielding a crude prevalence rate of 106.6/100000 (95% CI: 94-120). Prevalence was higher in women (140.8/100000) than in men (68.5/100000). The age-adjusted prevalence rate standardized to the European population was 96.0/100000. MOG G511C polymorphism did not differ between cases and controls. HLA-DRB1*15 frequency was 58/155 (37%) in cases and 24/157 (15%) in controls (P<0.001). There was no HLA-DRB1*15 influence on susceptibility to other autoimmune disorders. The high MS prevalence in Verona confirms Italy as a high-risk area with a homogenous distribution across the country. HLA-DRB1*15 is a relevant MS susceptibility locus in the Italian population, possibly with little influence on the occurrence of concomitant autoimmune disorders. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

PREVALENCE OF COMBINATORIAL CYP2C9 AND VKORC1 GENOTYPES IN PUERTO RICANS: IMPLICATIONS FOR WARFARIN MANAGEMENT IN HISPANICS

PubMed Central

Duconge, Jorge; Cadilla, Carmen L.; Windemuth, Andreas; Kocherla, Mohan; Gorowski, Krystyna; Seip, Richard L.; Bogaard, Kali; Renta, Jessica Y.; Piovanetti, Paola; D’Agostino, Darrin; Santiago-Borrero, Pedro J.; Ruaño, Gualberto

2010-01-01

Polymorphisms in the cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) genes significantly alter the effective warfarin dose. We determined the frequencies of alleles, single carriers, and double carriers of single nucleotide polymorphisms (SNPs) in the CYP2C9 and VKORC1 genes in a Puerto Rican cohort and gauged the impact of these polymorphisms on warfarin dosage using a published algorithm. A total of 92 DNA samples were genotyped using Luminex® x-MAP technology. The polymorphism frequencies were 6.52%, 5.43% and 28.8% for CYP2C9 *2, *3 and VKORC1-1639 G>A polymorphisms, respectively. The prevalence of combinatorial genotypes was 16% for carriers of both the CYP2C9 and VKORC1 polymorphisms, 9% for carriers of CYP2C9 polymorphisms, 35% for carriers of the VKORC1 polymorphism, and the remaining 40% were non-carriers for either gene. Based on a published warfarin dosing algorithm, single, double and triple carriers of functionally deficient polymorphisms predict reductions of 1.0–1.6, 2.0–2.9, and 2.9–3.7 mg/day, respectively, in warfarin dose. Overall, 60% of the population carried at least a single polymorphism predicting deficient warfarin metabolism or responsiveness and 13% were double carriers with polymorphisms in both genes studied. Combinatorial genotyping of CYP2C9 and VKORC1 can allow for individualized dosing of warfarin among patients with gene polymorphisms, potentially reducing the risk of stroke or bleeding. PMID:20073138

MTHFR polymorphisms in Puerto Rican children with isolated congenital heart disease and their mothers

PubMed Central

García-Fragoso, Lourdes; García-García, Inés; Leavitt, Gloria; Renta, Jessicca; Ayala, Miguel A.; Cadilla, Carmen L.

2010-01-01

Congenital heart defects (CHD) are among the most common birth defects. There is evidence suggesting that polymorphisms in folate metabolism could alter susceptibility to CHD. The MTHFR 677TT genotype has been associated with the development of structural congenital heart malformations. The objective of this study was to identify common polymorphisms in the MTHFR gene in children with isolated CHD and their mothers. The DNA analysis for the C677T and A1298C mutations was performed. The study group included 27 mothers, 27 children with CHD, and 220 controls. The prevalence of the TT polymorphism was higher in mothers (22%) than in controls (10%). Compound heterozygosity for both polymorphisms was 3.7 times more common in children with CHD than in the newborn controls. Mothers of children with CHD were more likely to be compound heterozygotes. The higher prevalence of C677T polymorphisms in mothers of children with CHD and of compound heterozygosity for both polymorphisms suggests the possible role of folic acid in the prevention of CHD. Due to the relation of this enzyme to folate metabolism, current folate recommendations for women in childbearing age in Puerto Rico to reduce neural tube defects may need to be extended to the prevention of CHD. PMID:20657745

MTHFR polymorphisms in Puerto Rican children with isolated congenital heart disease and their mothers.

PubMed

García-Fragoso, Lourdes; García-García, Inés; Leavitt, Gloria; Renta, Jessicca; Ayala, Miguel A; Cadilla, Carmen L

2010-03-01

Congenital heart defects (CHD) are among the most common birth defects. There is evidence suggesting that polymorphisms in folate metabolism could alter susceptibility to CHD. The MTHFR 677TT genotype has been associated with the development of structural congenital heart malformations. The objective of this study was to identify common polymorphisms in the MTHFR gene in children with isolated CHD and their mothers. The DNA analysis for the C677T and A1298C mutations was performed. The study group included 27 mothers, 27 children with CHD, and 220 controls. The prevalence of the TT polymorphism was higher in mothers (22%) than in controls (10%). Compound heterozygosity for both polymorphisms was 3.7 times more common in children with CHD than in the newborn controls. Mothers of children with CHD were more likely to be compound heterozygotes. The higher prevalence of C677T polymorphisms in mothers of children with CHD and of compound heterozygosity for both polymorphisms suggests the possible role of folic acid in the prevention of CHD. Due to the relation of this enzyme to folate metabolism, current folate recommendations for women in childbearing age in Puerto Rico to reduce neural tube defects may need to be extended to the prevention of CHD.

Association of Matrix Metalloproteinase-1 Polymorphisms with Risk of COPD and Lung Cancer and Survival in Lung Cancer

PubMed Central

ENEWOLD, LINDSEY; MECHANIC, LEAH E.; BOWMAN, ELISE D.; PLATZ, ELIZABETH A.; ALBERG, ANTHONY J.

2013-01-01

Background The primary risk factor for chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC) is cigarette smoking but shared susceptibility factors, such as variations in the matrix metalloproteinase-1 (MMP1) gene, may also underlie both diseases. Materials and Methods Cases with prevalent COPD (n=167), incident NSCLC (n=242), or prevalent COPD plus incident NSCLC (n=128) were compared to disease-free controls (n=338) to assess six MMP1 polymorphisms. The association between these polymorphisms and survival in NSCLC was also evaluated. Results Rs11292517 among African-Americans [odds ratio (OR)=5.48, 95% confidence interval (CI)=1.17–25.72] and rs2071230 among Caucasians (OR=2.51, 95% CI=1.09–5.77) appeared to be associated with NSCLC risk in the presence of COPD. Rs470558 appeared to be associated with survival in NSCLC among African-Americans (hazard ratio=3.94; 95%CI=1.14–13.63). No associations remained after adjusting for multiple comparisons. Conclusion Polymorphisms in MMP1 were not consistently associated with prevalent COPD or incident NSCLC nor with survival in NSCLC. PMID:22993337

Cassava tissue culture and long-term preservation

USDA-ARS?s Scientific Manuscript database

Cassava (Manihot esculenta Crantz) is cultivated mainly for its starchy roots as an important staple food for the tropics. M. esculenta is the only cultivated species in the genus Manihot, which contains 98 species, mostly native to Brazil. In recent years several research groups have reported metho...

Camelina sativa defatted seed meal contains both alkyl sulfinyl glucosinolates and quercetin that synergize bioactivity

USDA-ARS?s Scientific Manuscript database

Camelina sativa L. Crantz is under development as a novel oil-seed crop, yet bioefficacy of camelina phytochemicals is unknown. Defatted camelina seed meal contains two major aliphatic glucosinolates (GSL), glucoarabin (9-(methylsulfinyl)nonylglucosinolate; GSL 9) and glucocamelinin (10-(methylsulfi...

DNA polymorphism analysis of candidate genes for type 2 diabetes mellitus in a Mexican ethnic group.

PubMed

Flores-Martínez, S E; Islas-Andrade, S; Machorro-Lazo, M V; Revilla, M C; Juárez, R E; Mújica-López, K I; Morán-Moguel, M C; López-Cardona, M G; Sánchez-Corona, J

2004-01-01

Type 2 diabetes mellitus is a complex metabolic disorder resulting from the action and interaction of many genetic and environmental factors. It has been reported that polymorphisms in genes involved in the metabolism of glucose are associated with the susceptibility to develop type 2 diabetes mellitus. Although the risk of developing type 2 diabetes mellitus increases with age, as well as with obesity and hypertension, its prevalence and incidence are different among geographical regions and ethnic groups. In Mexico, a higher prevalence and incidence has been described in the south of the country, and differences between urban and rural communities have been observed. We studied 73 individuals from Santiago Jamiltepec, a small indigenous community from Oaxaca State, Mexico. This population has shown a high prevalence of type 2 diabetes mellitus, and the aim of this study was to analyze the relationship between the Pst I (insulin gene), Nsi I (insulin receptor gene) and Gly972Arg (insulin receptor substrate 1 gene) polymorphisms and type 2 diabetes mellitus, obesity and hypertension in this population. Clinical evaluation consisted of BMI and blood pressure measurements, and biochemical assays consisted of determination of fasting plasma insulin and glucose levels. PCR and restriction enzyme digestion analysis were applied to genomic DNA to identify the three polymorphisms. From statistical analysis carried out here, individually, the Pst I, Nsi I and Gly972Arg polymorphisms were not associated with the type 2 diabetes, obese or hypertensive phenotypes in this population. Nevertheless, there was an association between the Nsi I and Pst I polymorphisms and increased serum insulin levels.

Frequency of CYP450 enzyme gene polymorphisms in the Greek population: review of the literature, original findings and clinical significance.

PubMed

Ragia, Georgia; Giannakopoulou, Efstathia; Karaglani, Makrina; Karantza, Ioanna-Maria; Tavridou, Anna; Manolopoulos, Vangelis G

2014-01-01

The cytochrome P450 (CYP450) enzyme family is involved in the oxidative metabolism of many therapeutic drugs and various endogenous substrates. These enzymes are highly polymorphic. Prevalence of CYP450 enzyme gene polymorphisms vary among different populations and substantial inter- and intra-ethnic variability in frequency of CYP450 enzyme gene polymorphisms has been reported. This paper provides an overview and investigation of CYP450 genotypic and phenotypic reports published in the Greek population.

Cassava haplotype map highlights fixation of deleterious mutations during clonal propagation

USDA-ARS?s Scientific Manuscript database

Cassava (Manihot esculenta Crantz) is an important staple food crop in Africa and South America whose fitness may be severely reduced by ubiquitous deleterious variation. To evaluate these deleterious mutations in cassava genome, we constructed a cassava haplotype map by deep sequencing of 241 diver...

Storage root of cassava: Morphological types, anatomy, formation, growth, development and harvest time

USDA-ARS?s Scientific Manuscript database

Cassava (Manihot esculenta, Crantz) is considered a starchy root crop that provides staple food for millions of people in tropical and subtropical regions of the world. Research efforts are directed towards genetic breeding and cultivation of cassava to improve cassava storage root starch production...

Intensifying production in the northern Corn Belt by incorporating cash cover crops

USDA-ARS?s Scientific Manuscript database

Relay cropping soybean with winter camelina (Camelina sativa L. Crantz) and pennycress (Thlaspi arvense L.) in corn and soybean rotations in the northern Corn Belt, USA provides ecosystem services and is economically viable. However, questions remain regarding the optimum time to interseed these cov...

Winter camelina: Crop growth, seed yield and quality response to genotype and sowing rate

USDA-ARS?s Scientific Manuscript database

Winter camelina [Camelina sativa (L.) Crantz] is a freeze-hardy, early maturing, winter annual crop that allows potential for dual cropping options in short-season temperate environments. However, little is known about genotypic variation of winter camelina or best management for its production. Tra...

Angiotensin-converting enzyme activity in Cavalier King Charles Spaniels with an ACE gene polymorphism and myxomatous mitral valve disease.

PubMed

Meurs, Kathryn M; Olsen, Lisbeth H; Reimann, Maria J; Keene, Bruce W; Atkins, Clarke E; Adin, Darcy; Aona, Brent; Condit, Julia; DeFrancesco, Teresa; Reina-Doreste, Yamir; Stern, Joshua A; Tou, Sandra; Ward, Jessica; Woodruff, Kathleen

2018-02-01

Myxomatous mitral valve disease (MMVD) is the most common heart disease in the dog. It is particularly common in the Cavalier King Charles Spaniel (CKCS) breed and affected dogs are frequently managed with angiotensin-converting enzyme inhibitors (ACE-I). We have previously identified a canine ACE gene polymorphism associated with a decrease in angiotensin-converting enzyme (ACE) activity. The aim of this study was to evaluate for the prevalence of the ACE polymorphism in CKCS with mitral valve disease and to determine whether the presence of the polymorphism is associated with alterations in ACE activity at different stages of cardiac disease. Seventy-three dogs with a diagnosis of mitral valve disease were evaluated and a blood sample was drawn for ACE polymorphism genotyping and ACE activity measurement. Forty-three dogs were homozygous for the ACE polymorphism; five were heterozygous and 25 were homozygous wild type. The mean age and the median severity of disease were not different for dogs with the polymorphism and dogs with the wild-type sequence. The median baseline ACE activity was significantly lower for the ACE polymorphism (27.0 U/l) than the wild-type sequence dogs (31.0 U/l) (P=0.02). Dogs with more severe disease and the ACE polymorphism had significantly lower levels of ACE activity than dogs with the wild-type sequence (P=0.03). The CKCS appears to have a high prevalence of the ACE variant. Dogs with the ACE variant had lower levels of ACE activity even in more advanced mitral valve disease than dogs without the variant. The clinical significance of this finding and its impact on the need for ACE-I in dogs with the polymorphism and heart disease deserves further study.

Frequency of LCT -13910C>T single nucleotide polymorphism associated with adult-type hypolactasia/lactase persistence among Brazilians of different ethnic groups.

PubMed

Mattar, Rejane; Monteiro, Maria S; Villares, Cibele A; Santos, Aníbal F; Silva, Joyce M K; Carrilho, Flair J

2009-10-02

Adult-type hypolactasia, the physiological decline of lactase some time after weaning, was previously associated with the LCT -13910C>T polymorphism worldwide except in Africa. Lactase non-persistence is the most common phenotype in humans, except in northwestern Europe with its long history of pastoralism and milking. We had previously shown association of LCT -13910C>T polymorphism with adult-type hypolactasia in Brazilians; thus, we assessed its frequency among different Brazilian ethnic groups. We investigated the ethnicity-related frequency of this polymorphism in 567 Brazilians [mean age, 42.1 +/- 16.8 years; 157 (27.7%) men]; 399 (70.4%) White, 50 (8.8%) Black, 65 (11.5%) Brown, and 53 (9.3%) Japanese-Brazilian. DNA was extracted from leukocytes; LCT -13910C>T polymorphism was analyzed by PCR-restriction fragment length polymorphism. Prevalence of the CC genotype associated with hypolactasia was similar (57%) among White and Brown groups; however, prevalence was higher among Blacks (80%) and those of Japanese descent (100%). Only 2 (4%) Blacks had TT genotype, and 8 (16%) had the CT genotype. Assuming an association between CC genotype and hypolactasia, and CT and TT genotypes with lactase persistence, 356 (62.8%) individuals had hypolactasia and 211 (37.2%) had lactase persistence. The White and Brown groups had the same hypolactasia prevalence (approximately 57%); nevertheless, was 80% among Black individuals and 100% among Japanese-Brazilians (P < 0.01). The lactase persistence allele, LCT -13910T, was found in about 43% of both White and Brown and 20% of the Black Brazilians, but was absent among all Japanese Brazilians studied.

Status of vitamin B-12 and B-6 but not of folate, homocysteine and the methylenetetrahydrofolate reductase C677T polymorphism are associated with impaired cognition and depression in adults

USDA-ARS?s Scientific Manuscript database

The C677T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene differs in frequency in different ethnic groups which have differing prevalence of age-related cognitive impairments. We used a battery of neuropsychological tests to examine association of the MTHFR C677T polymorphism w...

UV-visible scanning spectrophotometry and chemometric analysis as tools for carotenoids analysis in cassava genotypes (Manihot esculenta Crantz).

PubMed

Moresco, Rodolfo; Uarrota, Virgílio Gavicho; Pereira, Aline; Tomazzoli, Maíra Maciel; Nunes, Eduardo da C; Peruch, Luiz Augusto Martins; Gazzola, Jussara; Costa, Christopher; Rocha, Miguel; Maraschin, Marcelo

2015-10-21

In this study, the metabolomics characterization focusing on the carotenoid composition of ten cassava (Manihot esculenta) genotypes cultivated in southern Brazil by UV-visible scanning spectrophotometry and reverse phase-high performance liquid chromatography was performed. Cassava roots rich in β-carotene are an important staple food for populations with risk of vitamin A deficiency. Cassava genotypes with high pro-vitamin A activity have been identified as a strategy to reduce the prevalence of deficiency of this vitamin. The data set was used for the construction of a descriptive model by chemometric analysis. The genotypes of yellow-fleshed roots were clustered by the higher concentrations of cis-β-carotene and lutein. Inversely, cream-fleshed roots genotypes were grouped precisely due to their lower concentrations of these pigments, as samples rich in lycopene (red-fleshed) differed among the studied genotypes. The analytical approach (UV-Vis, HPLC, and chemometrics) used showed to be efficient for understanding the chemodiversity of cassava genotypes, allowing to classify them according to important features for human health and nutrition.

UV-visible scanning spectrophotometry and chemometric analysis as tools for carotenoids analysis in cassava genotypes (Manihot esculenta Crantz).

PubMed

Moresco, Rodolfo; Uarrota, Virgílio G; Pereira, Aline; Tomazzoli, Maíra; Nunes, Eduardo da C; Martins Peruch, Luiz Augusto; Gazzola, Jussara; Costa, Christopher; Rocha, Miguel; Maraschin, Marcelo

2015-12-01

In this study, the metabolomics characterization focusing on the carotenoid composition of ten cassava (Manihot esculenta) genotypes cultivated in southern Brazil by UV-visible scanning spectrophotometry and reverse phase-high performance liquid chromatography was performed. Cassava roots rich in β-carotene are an important staple food for populations with risk of vitamin A deficiency. Cassava genotypes with high pro-vitamin A activity have been identified as a strategy to reduce the prevalence of deficiency of this vitamin. The data set was used for the construction of a descriptive model by chemometric analysis. The genotypes of yellow-fleshed roots were clustered by the higher concentrations of cis- β-carotene and lutein. Inversely, cream-fleshed roots genotypes were grouped precisely due to their lower concentrations of these pigments, as samples rich in lycopene (redfleshed) differed among the studied genotypes. The analytical approach (UV-Vis, HPLC, and chemometrics) used showed to be efficient for understanding the chemodiversity of cassava genotypes, allowing to classify them according to important features for human health and nutrition.

Environmental impact assessment of double- and relay-cropping with winter camelina in the northern Great Plains, USA

USDA-ARS?s Scientific Manuscript database

Recent findings indicate that double- or relay-cropping winter camelina (Camelina sativa L. Crantz.) with feed or food crops can increase yield per area, improve energy balance, and provide several ecosystem services. Double-cropping can help balance food and energy production. The objective of this...

Regional heritability mapping provides insights into dry matter (DM) content in African white and yellow cassava populations

USDA-ARS?s Scientific Manuscript database

The HarvestPlus program for cassava (Manihot esculenta Crantz) fortifies cassava with beta-carotene by breeding for carotene-rich tubers (yellow cassava). However, a negative correlation between yellowness and dry matter (DM) content has been identified. Here, we investigated the genetic control of ...

Integrating winter camelina into maize and soybean cropping systems

USDA-ARS?s Scientific Manuscript database

Camelina [Camelina sativa (L.) Crantz.] is an industrial oilseed crop in the Brassicaceae family with multiple uses. Currently, camelina is not used as a cover crop, but it has the potential to be used as such in maize (Zea mays L.)-soybean [Glycine max (L.) Merr.] systems. The objectives of this st...

Cultivar and planting date selection for relay-cropping soybean with winter oilseeds

USDA-ARS?s Scientific Manuscript database

Double- and relay-cropping soybean with winter camelina (Camelina sativa L. Crantz) and pennycress (Thlaspi arvense L.) have been shown to be viable cropping systems for the Upper Midwest. Relaying soybean with these winter oilseeds can result in greater total seed yield (i.e., both combined) and ec...

Some Nutritional Characteristics of Enzymatically Resistant Maltodextrin from Cassava (Manihot esculenta Crantz) Starch.

PubMed

Toraya-Avilés, Rocío; Segura-Campos, Maira; Chel-Guerrero, Luis; Betancur-Ancona, David

2017-06-01

Cassava (Manihot esculenta Crantz) native starch was treated with pyroconversion and enzymatic hydrolysis to produce a pyrodextrin and an enzyme-resistant maltodextrin. Some nutritional characteristics were quantified for both compounds. Pyroconversion was done using a 160:1 (p/v) starch:HCl ratio, 90 °C temperature and 3 h reaction time. The resulting pyrodextrin contained 46.21% indigestible starch and 78.86% dietary fiber. Thermostable α-amylase (0.01%) was used to hydrolyze the pyrodextrin at 95 °C for 5 min. The resulting resistant maltodextrin contained 24.45% dextrose equivalents, 56.06% indigestible starch and 86.62% dietary fiber. Compared to the cassava native starch, the pyrodextrin exhibited 56% solubility at room temperature and the resistant maltodextrin 100%. The glycemic index value for the resistant maltodextrin was 59% in healthy persons. Its high indigestible starch and dietary fiber contents, as well as its complete solubility, make the resistant maltodextrin a promising ingredient for raising dietary fiber content in a wide range of foods, especially in drinks, dairy products, creams and soups.

In vitro assessment of the genotoxic and cytotoxic effects of boiled juice (tucupi) from Manihot esculenta Crantz roots.

PubMed

Cunha, L A; Mota, T C; Cardoso, P C S; Alcântara, D D F Á; Burbano, R M R; Guimarães, A C; Khayat, A S; Rocha, C A M; Bahia, M O

2016-10-05

The population of Pará (a state in Brazil) has a very characteristic food culture, as a majority of the carbohydrates consumed are obtained from cassava (Manihot esculenta Crantz) derivatives. Tucupi is the boiled juice of cassava roots that plays a major role in the culinary footprint of Pará. Before boiling, this juice is known as manipueira and contains linamarin, a toxic glycoside that can decompose to hydrogen cyanide. In this study, the cytotoxic and genotoxic effects of tucupi on cultured human lymphocytes were assessed using the comet assay and detection of apoptosis and necrosis by differential fluorescent staining with acridine orange-ethidium bromide. Tucupi concentrations (v/v) were determined using the methylthiazole tetrazolium biochemical test. Concentrations of tucupi that presented no genotoxic effects (2, 4, 8, and 16%) were used in our experiments. The results showed that under our study conditions, tucupi exerted no genotoxic effects; however, cytotoxic effects were observed with cell death mainly induced by necrosis. These effects may be related to the presence of hydrogen cyanide in the juice.

Household utilization of Manioc (Manihot esculenta Crantz) in Northern Mozambique.

PubMed

Muoki, Penina N; Maziya-Dixon, Bussie

2010-01-01

Mozambique is ranked ninth of top manioc (Manihot esculenta Crantz) producing countries in the world. Manioc roots are a staple to people living in the northern part of the country. Despite this, information on production, utilization, postharvest handling, and marketing is scarce. The purpose of this baseline study was to document selected information on manioc, from the production to marketing stage. To gather this information, 70 focus groups consisting of 1,724 participants purposely sampled from 10 districts were engaged in discussions using a questionnaire. The results show that manioc is the most important crop in terms of contribution to household food security and income in the region. Both men and women participate in the delivery of manioc production chain. Typically, 5 to 15 varieties identified by local language can be found on most farms in the study area. Manioc leaves and roots are the parts of the plant used as human food. Sun dried manioc roots are principally marketed within the locality of production by individual farmers. This baseline study suggests the need for location-targeted interventions as the farmers reported varied challenges along the manioc production chain.

Apolipoprotein E polymorphism in elderly Japanese-Brazilian immigrants does not explain the reduced cardiovascular risk factor incidence.

PubMed

Terra, N; Moriguchi, Y; Bittencourt, L; Trois, R S; Piccoli, J E C; Cruz, I B M

2011-09-09

Study of immigrant populations may contribute to a better understanding of the epidemiology of diseases associated with the aging process. We examined the prevalence of cardiovascular risk factors, including apolipoprotein E (ApoE) polymorphism, in elderly subjects who were born in Japan, migrated to South Brazil and have lived in that region for over 40 years, versus a group of elderly, locally born Brazilians living in the same region. These Japanese subjects came to Brazil after World War II (1950-1960) from several Japanese cities, mainly Nagasaki, Kumamoto and Hokkaido. Among 1007 subjects genotyped for ApoE polymorphism, we selected 540 elderly subjects (>60 years old), consisting of 270 Japanese-Brazilians and 270 Brazilians of European ancestry from Rio Grande do Sul State (Gaucha population). The Japanese-Brazilian group had significantly lower prevalences of obesity, type 2 diabetes mellitus, dyslipidemia, and metabolic syndrome than did the Gaucho population group. ApoE polymorphism frequencies were similar in the two groups. The differences in cardiovascular risk factors observed in the two populations cannot be explained by ApoE polymorphism; they could be related to conservation of Japanese lifestyle habits, such as diet.

H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism: clinical and pathologic features in wild-type and E211K cattle following intracranial inoculation

USDA-ARS?s Scientific Manuscript database

In 2006 an H-type bovine spongiform encephalopathy (BSE) case was reported in an animal with an unusual polymorphism (E211K) in the prion protein gene. Although the prevalence of this polymorphism is low, cattle carrying the K211 allele are predisposed to rapid onset of H-type BSE when exposed. The ...

Meta-analysis of factor V Leiden and prothrombin G20210A polymorphism in migraine.

PubMed

Lippi, Giuseppe; Mattiuzzi, Camilla; Cervellin, Gianfranco

2015-01-01

Migraine is a frequent and disabling condition, which exhibits a substantial genetic background and is frequently associated with abnormalities of primary and secondary hemostasis. We performed a systematic literature search and a meta-analysis of available data about the potential associations between migraine and factor V (FV) Leiden or prothrombin (FII) G20210A gene polymorphism. The final number of studies included was 15 (all cross-sectional) about migraine and FV Leiden, and 12 (all cross-sectional) about migraine and FII G20210A polymorphism, with broad inter-study heterogeneity (I², 82 and 85%). The cumulative prevalence of the FV 1691A allele was found to be similar between cases (n = 1450; 4.9%) and controls (n = 3468; 4.7%; P = 0.74). The cumulative prevalence of the FII 20210A allele was also found to be similar between cases (n = 1226; 4.2%) and controls (n = 3144; 4.5%; P = 0.59). Nevertheless, sub-analysis of studies in adults and children revealed that both polymorphisms were not associated with migraine in adults, but FV Leiden and the FII 20210A allele were approximately two-fold more prevalent in children with migraine than in those without. In conclusion, despite migraine exhibits a clear neurovascular origin and is frequently associated with thrombotic disorders, isolate thrombophilic mutations seem to play a negligible pathogenetic role in this condition in adults, whereas the increased prevalence of FV Leiden and the FII 20210A allele in children with migraine deserves further scrutiny.

Associations of recurrent miscarriages with chromosomal abnormalities, thrombophilia allelic polymorphisms and/or consanguinity in Saudi Arabia.

PubMed

Turki, Rola F; Assidi, Mourad; Banni, Huda A; Zahed, Hanan A; Karim, Sajjad; Schulten, Hans-Juergen; Abu-Elmagd, Muhammad; Rouzi, Abdulrahim A; Bajouh, Osama; Jamal, Hassan S; Al-Qahtani, Mohammed H; Abuzenadah, Adel M

2016-10-10

Recurrent pregnancy loss (RPL) or recurrent spontaneous abortion is an obstetric complication that affects couples at reproductive age. Previous reports documented a clear relationship between parents with chromosomal abnormalities and both recurrent miscarriages and infertility. However, limited data is available from the Arabian Peninsula which is known by higher rates of consanguineous marriages. The main goal of this study was to determine the prevalence of chromosomal abnormalities and thrombophilic polymorphisms, and to correlate them with RPL and consanguinity in Saudi Arabia. Cytogenetic analysis of 171 consent patients with RPL was performed by the standard method of 72-h lymphocyte culture and GTG banding. Allelic polymorphisms of three thrombophilic genes (Factor V Leiden, Prothrombin A20210G, MTHFR C677T) were performed using PCR-RFLP (restriction fragment length polymorphism) and gel electrophoresis. Data analysis revealed that 7.6 % of patients were carrier of numerical or structural chromosomal abnormalities. A high rate of translocations (46 %) was associated to increased incidence of RPL. A significant correlation between consanguineous RPL patients and chromosomal abnormalities (P < 0.05) was found. Both Factor V Leiden and Prothrombin A20210G allelic polymorphisms were significantly associated with a higher prevalence of RPL. This study demonstrated a strong association between RPL and the prevalence of chromosomal abnormalities and inherited thrombophilia. Given the high rate of consanguineous marriages in the Saudi population, these results underline the importance of systematic cytogenetic investigation and genetic counseling preferably at the premarital stage or at least during early pregnancy phase through preimplantation genetic diagnosis (PGD).

Associations of fractalkine receptor (CX3CR1) and CCR5 gene variants with hypertension, diabetes and atherosclerosis in chronic renal failure patients undergoing hemodialysis.

PubMed

Bagci, Binnur; Bagci, Gokhan; Huzmeli, Can; Sezgin, Ilhan; Ozdemir, Ozturk

2016-07-01

We aimed to investigate the associations of fractalkine receptor (CX3CR1) V249I, T280M and CCR5-59029 A/G gene polymorphisms in chronic renal failure (CRF) subjects undergoing hemodialysis and to evaluate possible associations of these polymorphisms with hypertension (HT), diabetes mellitus (DM) and atherosclerosis (AS). A total of 225 CRF subjects undergoing hemodialysis and 201 healthy controls were enrolled in the study. CRF subjects were divided into three major subgroups according to comorbidities including HT (n = 127), DM (n = 65) and AS (n = 33). Genotyping was done using polymerase chain reaction-restriction fragment length polymorphism method. The II genotype and I allele frequencies of CX3CR1 V249I polymorphism were found significantly more frequent in CRF subjects, CRF subjects with DM and CRF subjects with AS compared with controls (p < 0.05 for all comparisons). G allele frequency of CCR5 polymorphism was found significantly more prevalent in CRF subjects with DM than that of controls. Further, GG genotype and G allele frequencies of CCR5 polymorphism were significantly more prevalent in CRF subjects with AS compared with controls (p < 0.05). We also explored these polymorphisms among CRF subjects with and without following comorbidities: HT, DM, AS. We found significant association between CRF subjects with HT and without HT in terms of genotype and allele frequencies of V249I polymorphism (p < 0.05). CX3CR1 T280M polymorphism was not found significantly different in none of the comparisons. These data demonstrate possible associations between CX3CR1 V249I and CCR5-59029 A/G polymorphisms and/or HT, DM and AS in CRF subjects.

Genetic Risk Conferred from Single Nucleotide Polymorphisms Towards Type II Diabetes Mellitus

DTIC Science & Technology

2013-02-14

prediabetes ” 4 . Among MHS beneficiaries ages 40 – 49, the prevalence of obesity (e.g., body mass index > 30kg/m 3 ) has been recently reported to...polymorphisms in WFS1 on prediabetic phenotypes in a population-based sample of middle-aged people with normal and abnormal glucose regulation

Development of gene polymorphisms in meditators of nonalcoholic fatty liver disease

PubMed Central

Wang, Chun; Gong, Jianping; Wu, Hao

2017-01-01

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, the morbidity of which closely correlates with diversity of ethnicity, minority, family and location. Its histology spans from simple steatosis, to nonalcoholic steatohepatitis, which ultimately results in fibrosis, cirrhosis and hepatocellular carcinoma. The accelerating prevalence of NAFLD is due to an incremental incidence of metabolic syndrome that is distinguished by dyslipidemia, glucose impairment, obesity, excessive oxidative stress and adipocytokine impairment. Additionally, the pathogenesis of NAFLD is thought to be a multifactorial and complicated disease associated with lifestyle habits, nutritional factors and genetics. However, the pathogenesis and underlying mechanism in the development of NAFLD caused by genetics remains unclear. People have been increasingly emphasizing on the relationship between NAFLD and gene polymorphisms in recent years, with the aim of having a comprehensive elucidation of associated gene polymorphisms influencing the pathogenesis of the disease. In the current article, the authors attempted to critically summarize the most recently identified gene polymorphisms from the facets of glucose metabolism, fatty acid metabolism, oxidative stress and related cytokines in NAFLD that contribute to promoting the progression of the disease. PMID:28804621

Evolutionary trade-offs and the structure of polymorphisms.

PubMed

Sheftel, Hila; Szekely, Pablo; Mayo, Avi; Sella, Guy; Alon, Uri

2018-05-26

Populations of organisms show genetic differences called polymorphisms. Understanding the effects of polymorphisms is important for biology and medicine. Here, we ask which polymorphisms occur at high frequency when organisms evolve under trade-offs between multiple tasks. Multiple tasks present a problem, because it is not possible to be optimal at all tasks simultaneously and hence compromises are necessary. Recent work indicates that trade-offs lead to a simple geometry of phenotypes in the space of traits: phenotypes fall on the Pareto front, which is shaped as a polytope: a line, triangle, tetrahedron etc. The vertices of these polytopes are the optimal phenotypes for a single task. Up to now, work on this Pareto approach has not considered its genetic underpinnings. Here, we address this by asking how the polymorphism structure of a population is affected by evolution under trade-offs. We simulate a multi-task selection scenario, in which the population evolves to the Pareto front: the line segment between two archetypes or the triangle between three archetypes. We find that polymorphisms that become prevalent in the population have pleiotropic phenotypic effects that align with the Pareto front. Similarly, epistatic effects between prevalent polymorphisms are parallel to the front. Alignment with the front occurs also for asexual mating. Alignment is reduced when drift or linkage is strong, and is replaced by a more complex structure in which many perpendicular allele effects cancel out. Aligned polymorphism structure allows mating to produce offspring that stand a good chance of being optimal multi-taskers in at least one of the locales available to the species.This article is part of the theme issue 'Self-organization in cell biology'. © 2018 The Author(s).

[Association of single nucleotide polymorphism at interleukin-10 gene 1082 nt with the risk of gastric cancer in Chinese population].

PubMed

Zhou, Shao-zhang; Zhu, Wei-liang; Li, Ming-ying; Li, Hong-yi; Zhang, Ji-ren

2008-08-01

To study the association of single nucleotide polymorphism at interleukin-10 gene 1082 locus with Helicobacter pylori (Hp) infection and the risk of gastric cancer in high prevalent region (Shaanxi Province)aand low prevalence region (Guangdong Province) in China. The genomic DNA was extracted from the peripheral blood of 104 healthy individuals, 104 gastric cancer patients from Guangdong Province, and from 102 healthy volunteers and 102 gastric cancer patients in Shaanxi Province, China. The single nucleotide polymorphism at IL-10 gene 1082 locus was analyzed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The serum levels of anit-Hp IgG was measured by enzyme-linked immunosorbent assay. The frequencies of IL-10-1082 A/A, A/G and G/G genotypes in the 412 subjects were 86.7%, 10.7% and 2.4%, respectively. In the low prevalence region, the number of carriers of IL-10-1082 G* was much greater in the cancer patients than in the healthy controls (14.4% vs 7.7%, Chi2=4.02, P<0.05, OR=1.01, 95% CI=1.08-3.10). The presence of IL-10-1082 G* was associated with significantly increased risk of gastric cancer following Hp infection (Chi(2)=5.36, P<0.05, OR=6.0, 95% CI=1.23-17.52). In the high prevalence region, the frequency of IL-10-1082 G* was slightly higher among the cancer patients than in the healthy controls, but this difference was not statistically significant (12.7% vs 16.6%, P>0.05). The G* genotype of IL-10 gene 1082 locus may be associated with increased risk of gastric cancer in China.

High prevalence of three prothrombotic polymorphisms among Palestinians: factor V G1691A, factor II G20210A and methylenetetrahydrofolate reductase C677T.

PubMed

Hussein, Ayman S

2012-10-01

Factor V leiden G1691A/R506Q (FVL), prothrombin G20210A (FII) and methylenetetrahydrofolate reductase (MTHFR) C677T are related genetic risk factors for venous thromboembolism. Analysis for those mutations is increasingly being performed on patients exhibiting hypercoagulability. The objective of this study was to determine the prevalence of FVL, FII-G20210A and MTHFR-C677T polymorphisms and their coexistence among apparently healthy Palestinians. After institutional approval, 303 apparently healthy students from An-Najah University representative to North and South regions of West Bank with no previous history of cardiovascular diseases participated in this study. A uniform questionnaire was used to collect relevant information through personal interview with the subjects. The collected information included gender, age, smoking habits, weight and height, diseases such as diabetes, cardiovascular and family history of CVD. The frequencies of allelic distribution of the three prothrombotic polymorphisms factor V G1691A/R506Q), prothrombin G2010A, and MTHFR-C677T were 0.114, 0.050 and 0.071, respectively. The prevalence of the three thrombotic polymorphisms (FVL, FII G20210A and MTHFR-C677T) were 20.1, 9.1 and 13.8 %, respectively. Statistical analysis for factor V leiden showed no significant association between place of residence (P value = 0.953) and gender (P value >0.082). The data presented in this study showed the highest prevalence of FVL among healthy Palestinians compared to other populations and this important finding should be followed in terms of clinical significance.

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.

Association of Interleukin-10 gene promoter polymorphisms with obstructive sleep apnea.

PubMed

Özdaş, Sibel; Özdaş, Talih; Acar, Mustafa; Erbek, Selim S; Köseoğlu, Sabri; Göktürk, Gökhan; Izbirak, Afife

2016-05-01

Interleukin-10 (IL) is an anti-inflammatory cytokine that regulates normal sleep patterns, and recent studies have reported that it is a potential useful biomarker to identify presence and severity of sleep apnea syndrome (OSAS). Promoter polymorphisms of IL-10 gene have been associated with altered expression levels, which contributes to OSAS. The aim of this study was to determine the prevalence of -1082 G/A, -819 C/T, and -592 C/A promoter polymorphisms of IL-10 gene in individuals with OSAS and controls. An open-label study was performed in the Otorhinolaryngology and Sleep Disorders Outpatient Clinics. One hundred four cases with OSAS were included as the study group, and 78 individuals without OSAS were included as the controls. DNAs were extracted from peripheral blood leukocytes, and the sites that encompassed those polymorphisms were identified by DNA sequencing analyses. Data were analyzed with SNPStats and multifactor dimensionality reduction (MDR) software. The prevalence of OSAS was higher in males in the study group when compared to controls (P = 0.0003). The IL-10-1082 G/A, -819 C/T, and -592 C/A SNPs, and their minor alleles were associated with a significantly increased risk for OSAS compared to the controls (P ˂ 0.05 for all). Furthermore, ATA haplotype frequency was significantly higher in the study group compared to the control group, but the GCC haplotype frequency was lower (P = 0.0001 and P = 0.0001). As indicated in MDR analysis, combinations of IL-10 gene were associated with OSAS in single-, double-, and triple-locus analyses. The prevalences of the IL-10 gene promoter polymorphisms were different in OSAS patients and the controls in Turkish population. IL-10 gene polymorphisms may lead to altered inflammatory cascade, which might contribute to OSAS. Further studies on larger cohorts are needed to validate our findings.

Prevalence of genetic thrombophilic polymorphisms in the Sri Lankan population--implications for association study design and clinical genetic testing services.

PubMed

Dissanayake, Vajira H W; Weerasekera, Lakshini Y; Gammulla, C Gayani; Jayasekara, Rohan W

2009-10-01

We investigated the prevalence of genotypes/alleles of single nucleotide polymorphisms (SNP) and haplotypes defined by them in three genes in which variations are associated with venous thromboembolism in 80 Sinhalese, 80 Sri Lankan Tamils and 80 Moors in the Sri Lankan population and compared the SNP data with that of other populations in Southern India and haplotype data with that of HapMap populations. The genes and polymorphisms investigated were Methylenetetrahydrofolate reductase (MTHFR) - 677C>T (rs1801133), 1298A>C (rs1801131), 1317T>C, 1793G>A (rs2274976); Factor V (F5) - 1691G>A (rs6025) and 4070A>G (rs1800595); and prothrombin (F2) - 20210G>A (rs1799963). The polymorphisms were genotyped using PCR/RFLP methods. The prevalence of the variant alleles of each polymorphism in the Sinhalese, Tamils, and Moors was MTHFR 677T: Sinhalese - 13%, Tamils - 9%, Moors - 9%. 1317T>C: Sinhalese - 0%; Tamils - 0%; Moors - 0%. 1793A: Sinhalese - 19%, Tamils - 19%, Moors - 19%. F5 1691A: Sinhalese - 2%, Tamils - 3%, Moors - 2%. 4070G: Sinhalese - 6%, Tamils - 5%, Moors - 8%. F2 20210A: Sinhalese - 0%, Tamils - 0%, Moors - 0%. The frequencies observed were similar to data from other South Indian populations; the haplotype data showed haplotypes unique to the Sri Lankan population when compared to HapMap populations. rs9651118 was identified as a SNP that splits the haplotypes harbouring the functionally significant 677T allele in the MTHFR gene. This data would be useful in planning genetic association studies in the Sri Lankan population and in deciding on which genetic variants should be tested in a clinical genetic testing service.

Gender differences in the effects of ADH1B and ALDH2 polymorphisms on alcoholism.

PubMed

Kimura, Mitsuru; Miyakawa, Tomohiro; Matsushita, Sachio; So, Mirai; Higuchi, Susumu

2011-11-01

Gender differences are known to exist in the prevalence, characteristics, and course of alcohol dependence. Elucidating gender differences in the characteristics of alcohol dependence is important in gender-based medicine and may improve treatment outcomes. Many studies have shown that genetic factors are associated with the risk of alcohol dependence in both genders. Polymorphisms of alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) are strong genetic determinants of alcohol dependence. This study aimed to clarify gender differences in the effects of ADH1B and ALDH2 polymorphism on the development of alcohol dependence. Subjects were 200 female alcoholics and 415 male alcoholics hospitalized in Kurihama Alcoholism Center. Clinical information and background data were obtained by chart review. ALDH2 and ADH1B genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism method. The onset age of female alcoholics with inactive ALDH2 genotype was significantly lower than those with active ALDH2 genotype, but the onset age did not differ between the inactive and active ALDH2 group in male alcoholics. The difference in onset age between the ADH1B genotype groups did not reach significant levels. The prevalence of comorbid psychiatric disorders, including major depression, eating disorder, panic disorder, and borderline personality disorder, was significantly higher in female alcoholics with inactive ALDH2 or superactive ADH1B than in those with active ALDH2 or normal ADH1B. ALDH2 polymorphism appears to have contrasting effects on the development of alcoholism in women and men. One possible reason for this gender difference may be the high prevalence of psychiatric comorbidities in female alcoholics with inactive ALDH2. Copyright © 2011 by the Research Society on Alcoholism.

[Prevalence of gene polymorphisms associated with immune-dependent diseases in the populations of North Eurasia].

PubMed

Cherednichenko, A A; Trifonova, E A; Vagaitseva, K V; Bocharova, A V; Varzari, A M; Radzhabov, M O; Stepanov, V A

2015-01-01

The data on distribution of genetic diversity in gene polymorphisms associated with autoimmune and allergic diseases and with regulation of immunoglobulin E and cytokines levels in 26 populations of the Northern Eurasia is presented. Substantial correlation between the values of average expected heterozygosity by 44 gene polymorphisms with climatic and geographical factors has not been revealed. Clustering of population groups in correspondence with their geographic locations is observed. The degree of gene differentiation among populations and the selective neutrality of gene polymorphisms have been assessed. The results of our work evidence the substantial genetic diversity and differentiation of human populations by studied genes.

Isoelectric Focusing of Cassava Protoplasts

PubMed Central

Santana, María Angélica; Villegas, Leopoldo

1991-01-01

Cassava (Manihot esculenta Crantz) protoplast was analyzed by using isoelectric focusing techniques. Two populations, representing 68 and 32% of the total sample, with mean isoelectric points of 4.48 and 4.60, were obtained using mesophyll protoplasts. The use of this technique allows demonstration of a discontinuous distribution of protoplast isoelectric point from one species according to their surface potential. Images Figure 1 PMID:16667975

Marker-based estimates reveal significant non-additive effects in clonally propagated cassava (Manihot esculenta): implications for the prediction of total genetic value and the selection of varieties

USDA-ARS?s Scientific Manuscript database

In clonally propagated crops, non-additive genetic effects can be effectively exploited by the identification of superior genetic individuals as varieties. Cassava (Manihot esculenta Crantz) is a clonally propagated staple food crop that feeds hundreds of millions. We quantified the amount and natur...

A novel biochar from Manihot esculenta Crantz waste: application for the removal of Malachite Green from wastewater and optimization of the adsorption process.

PubMed

Beakou, Buscotin Horax; El Hassani, Kaoutar; Houssaini, Mohammed Amine; Belbahloul, Mounir; Oukani, Elhassan; Anouar, Abdellah

2017-09-01

The adsorptive removal of Malachite Green (MG) by a novel biochar namely Cassava Rind Carbon (CRC) was studied in a batch system. Moreover, Box-Behnken Response Surface Methodology was used to optimize operating conditions of the adsorption process. Characterization was done by Thermo Gravimetric Analysis (TGA), Attenuated Total Reflectance Fourier Transform Infra-Red Spectroscopy (ATR/FTIR), Brunauer-Emmett-Teller (BET) surface area, Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD) and pH zero charge point (pH ZCP ). The pseudo-second-order model and Langmuir model provided the best fit for kinetic and isotherm, respectively. The maximum capacity of dye adsorbed was 932.98 mg/g at 25 °C. The influence of temperature, the mass of adsorbent and the concentration of dye was studied. The optimal amount of adsorbed MG was 1,363.58 mg/g corresponding to 50 °C, 5 mg of CRC and 150 mg/L of dye. According to the high performance exhibited by CRC in this study, Manihot esculenta Crantz waste can be used as a better and low-cost biomass for wastewater decolourization.

Comparison of the effects of cassava (Manihot esculenta Crantz) organic cyanide and inorganic cyanide on muscle and bone development in a Nigerian breed of dog.

PubMed

Ibebunjo, C; Kamalu, B P; Ihemelandu, E C

1992-09-01

Effects of cassava (Manihot esculenta Crantz)-borne organic cyanide and inorganic cyanide in the form of sodium cyanide on bone and muscle development were investigated in eighteen dogs of Nigerian breed. After 16 weeks of stabilization in the laboratory from the time of purchase when the dogs were fed on the same diet, they were randomly assigned to three experimental groups of six dogs each. The control group was fed on rice while the other two groups were fed on either cassava (gari) or rice plus cyanide. The three diets were made isoenergetic and isonitrogenous by varying the quantity of meat incorporated into them. The results obtained after 14 weeks of feeding the respective diets indicated that there was retardation of muscle development in the gari-fed dogs. This may have resulted from gluconeogenesis from muscle protein associated with suppression of production of insulin by the pancreas in this group. The results indicated also that the effects of inorganic dietary cyanides on muscle development were different. Both forms of dietary cyanides, however, had no adverse effect on bone development.

High Incidence of Malaria Along the Sino-Burmese Border Is Associated With Polymorphisms of CR1, IL-1A, IL-4R, IL-4, NOS, and TNF, But Not With G6PD Deficiency.

PubMed

Ren, Na; Kuang, Ying-Min; Tang, Qiong-Lin; Cheng, Long; Zhang, Chun-Hua; Yang, Zao-Qing; He, Yong-Shu; Zhu, Yue-Chun

2015-10-01

Malaria is highly endemic in Yunnan Province, China, with the incidence of malaria being highest along the Sino-Burmese border. The aim of our study was to determine whether genetic polymorphisms are associated with the prevalence of malaria among Chinese residents of the Sino-Burmese border region. Fourteen otherwise healthy people with glucose-6-phosphate dehydrogenase (G6PD) deficiency, 50 malaria patients, and 67 healthy control subjects were included in our cross-sectional study. We analyzed the frequency of the G3093T and T520C single-nucleotide polymorphisms (SNPs) of CR1. Logistic regression was used to calculate the prevalence odds ratio (POR) and 95% confidence interval (CI) of malaria for the T520C SNP of CR1 and SNPs of G6PD, IL-4, IL-4R, IL-1A, NOS, CD40LG, TNF, and LUC7L. The frequency of the 3093T/3093T genotype of CR1 in the malaria group (0.16) was significantly higher than that in the control group (0.045, P < 0.05), and significantly lower than that in the G6PD deficiency group (0.43, P < 0.01). The frequency of the 520T/520T genotype of CR1 was significantly higher in the malaria patients (0.78) than that in the control group (0.67, P < 0.05) and G6PD-deficiency group (0.36, P < 0.05). The T allele of the T520C variant of CR1 was significantly associated with the prevalence of malaria (POR: 1.460; 95% CI: 0.703-3.034). Polymorphisms of G6PD did not significantly influence the prevalence malaria (P > 0.05). A GTGTGTC haplotype consisting of IL-1A (rs17561), IL-4 (rs2243250), TNF (rs1800750), IL-4R (rs1805015), NOS (rs8078340), CD40LG (rs1126535), and LUC7L (rs1211375) was significantly associated with the prevalence of malaria (POR: 1.822, 95% CI: 0.998-3.324). The 3093G/3093G and 520T/520T genotypes are the predominant genetic variants of CR1 among Chinese residents near the Sino-Burmese border, and the T allele of T520C is associated with the prevalence of malaria in this region. Although G6PD deficiency does not protect against malaria, it may diminish the association between malaria and the CR1 polymorphisms in this population. The GTGTGTC haplotype is also associated with the prevalence of malaria in this region.

Diversity of apolipoprotein E genetic polymorphism significance on cardiovascular risk is determined by the presence of metabolic syndrome among hypertensive patients.

PubMed

Teixeira, Andrei Alkmim; Marrocos, Mauro Sergio; Quinto, Beata Marie Redublo; Dalboni, Maria Aparecida; Rodrigues, Cassio Jose de Oliveira; Carmona, Silmara de Melo; Kuniyoshi, Mariana; Batista, Marcelo Costa

2014-11-20

Hypertension has a significant relevance as a cardiovascular risk factor. A consistent increase on world's Metabolic Syndrome (MetS) incidence has been associated with an epidemic cardiovascular risk in different populations. Dislipidemia plays a major role determining the epidemic CV burden attributed to MetS. Apolipoprotein E (ApoE) is involved on cholesterol and triglycerides metabolism regulation. Once ApoE polymorphism may influence lipid metabolism, it is possible that it brings on individual susceptibility consequences for the development of MetS and cardiovascular risk. The objective of the study is to measure the discriminatory power of ApoE polymorphism in determining cardiovascular risk stratification based on the presence MetS in a cohort of hypertensive patients. It was enrolled 383 patients, divided in two groups, classified by MetS presence (IDF criteria): Group 1: 266 patients with MetS (MetS +) and Group 2: 117 patients without Mets (MetS -). Patient's data were collected by clinical evaluation, physical exam, file reviews and laboratory testing. Polymorphic ApoE analysis was performed by PCR amplification. Groups were compared on clinical and laboratory characteristics as well as allele and genotype distribution towards ApoE polymorphism. Mets CVD prevalence was analysed according to E4 allele prevalence. The results evidenced 184 men (48%), 63,7% whites, 45,1% diabetics and 11,7% of patients were smokers. Mean age was 64,0 ± 12,0 years. When genotypic distribution was analyzed, E3/3 genotype and E3 allele frequencies were more prevalent. Among patients with MetS, we observed an independent association between CVD prevalence and E4 allele frequency (OR 2.42 (1.17- 5.0, p < 0,05)). On the opposite direction, in those without MetS, there was lesser CVD burden in E4 allele carriers (OR 0,14 (0,02-0,75)). These associations remained significant even after confounding factor corrections. The results presented demonstrate that the association between ApoE gene and CVD may be modulated by the presence of MetS, with an increased CV burden observed among E4 allele carriers with the syndrome. On the opposite way, E4 allele carriers without visceral obesity had lesser prevalence of CVD.

Prevalence and Molecular Characterization of Cyclospora cayetanensis, Henan, China

PubMed Central

Zhou, Yang; Lv, Biao; Wang, Qiang; Wang, Rongjun; Jian, Fuchun; Ning, Changshen; Fu, Kanda; Wang, Yaqiang; Qi, Meng; Yao, Huixia; Zhao, Jinfeng; Zhang, Xiaoshan; Sun, Yanru; Shi, Ke; Arrowood, Michael J.; Xiao, Lihua

2011-01-01

To determine prevalence of Cyclospora cayetanensis infection in Henan, China, we conducted a study of 11,554 hospital patients. Prevalence was 0.70% (95% confidence interval 0.70% ± 0.15%), with all age groups infected. Most cases were found in the summer. Minor sequence polymorphisms were observed in the 18S rRNA gene of 35 isolates characterized. PMID:22000362

Single-nucleotide polymorphisms in Toll-like receptor (TLR)-2, TLR4 and heat shock protein 70 genes and susceptibility to scrub typhus.

PubMed

Janardhanan, Jeshina; Joseph Martin, Sherry; Astrup, Elisabeth; Veeramanikandan, R; Aukrust, Pål; Abraham, Ooriapadickal C; Varghese, George M

2013-11-01

Scrub typhus is a highly prevalent bacterial infection in India and South Asia that is caused by Orientia tsutsugamushi. The innate immune response to infections is modulated by Toll-like receptors (TLRs) and heat shock proteins (HSPs). This study was done to assess the prevalence and possible association of TLR and HSP polymorphisms in scrub typhus. TLR4 Asp299Gly, TLR4 Thr399Ile, TLR2 Arg753Gln and HSP70-2 A1267G are single-nucleotide polymorphisms (SNPs) that may modulate their activities, and these SNPs were assessed in 137 scrub typhus patients and 134 controls by PCR restriction fragment length polymorphism. We found that the two TLR4 mutations, TLR4 D299G and TLR4T399I, were present in 19.5% and 22% of the study population, respectively, and was in significant linkage disequilibrium with a D' of 0.8. The TLR2 mutation was found to be rare, whereas the HSP A>G mutation was very common (77.5%). Compared with the controls, the prevalence of heterozygous genotype of the TLR4D299G SNP, but not any of the other SNPs, was significantly higher among scrub typhus patients. Further studies using a larger sample size and more candidate genes may better enable in determining the role of these associations in susceptibility and severity of scrub typhus.

Association of ghrelin polymorphisms with metabolic syndrome in Han Nationality Chinese.

PubMed

Xu, Ling-Ling; Xiang, Hong-Ding; Qiu, Chang-Chun; Xu, Qun

2008-06-01

To investigate the association of ghrelin gene polymorphisms with metabolic syndrome in Han Nationality Chinese. A total of 240 patients with metabolic syndrome and 427 adults aged above forty years were recruited. Genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism analysis. The allelic frequency of the Leu72Met polymorphism was 17.3% in the patient group and 11.9% in the control group (chi2 = 7.36, P = 0.007). Metabolic syndrome was more prevalent among carriers of the Met72 variant (43.8 vs 33.1%, age- and sex-adjusted odds ratio = 1.57, P = 0.01). No Arg51Gln variants were found in our study subjects. Rather than being associated with its individual components, Leu72Met polymorphism is associated with metabolic syndrome in the Han Nationality Chinese. Arg51Gln polymorphism is rare in the Han Nationality Chinese.

NS5A Sequence Heterogeneity and Mechanisms of Daclatasvir Resistance in Hepatitis C Virus Genotype 4 Infection.

PubMed

Zhou, Nannan; Hernandez, Dennis; Ueland, Joseph; Yang, Xiaoyan; Yu, Fei; Sims, Karen; Yin, Philip D; McPhee, Fiona

2016-01-15

Daclatasvir is an NS5A inhibitor approved for treatment of infection due to hepatitis C virus (HCV) genotypes (GTs) 1-4. To support daclatasvir use in HCV genotype 4 infection, we examined a diverse genotype 4-infected population for HCV genotype 4 subtype prevalence, NS5A polymorphisms at residues associated with daclatasvir resistance (positions 28, 30, 31, or 93), and their effects on daclatasvir activity in vitro and clinically. We performed phylogenetic analysis of genotype 4 NS5A sequences from 186 clinical trial patients and 43 sequences from the European HCV database, and susceptibility analyses of NS5A polymorphisms and patient-derived NS5A sequences by using genotype 4 NS5A hybrid genotype 2a replicons. The clinical trial patients represented 14 genotype 4 subtypes; most prevalent were genotype 4a (55%) and genotype 4d (27%). Daclatasvir 50% effective concentrations for 10 patient-derived NS5A sequences representing diverse phylogenetic clusters were ≤0.080 nM. Most baseline sequences had ≥1 NS5A polymorphism at residues associated with daclatasvir resistance; however, only 3 patients (1.6%) had polymorphisms conferring ≥1000-fold daclatasvir resistance in vitro. Among 46 patients enrolled in daclatasvir trials, all 20 with baseline resistance polymorphisms achieved a sustained virologic response. Circulating genotype 4 subtypes are genetically diverse. Polymorphisms conferring high-level daclatasvir resistance in vitro are uncommon before therapy, and clinical data suggest that genotype 4 subtype and baseline polymorphisms have minimal impact on responses to daclatasvir-containing regimens. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

Platelet glycoprotein Ibalpha Kozak polymorphism is associated with an increased risk of ischemic stroke.

PubMed

Baker, R I; Eikelboom, J; Lofthouse, E; Staples, N; Afshar-Kharghan, V; López, J A; Shen, Y; Berndt, M C; Hankey, G

2001-07-01

Platelets are pivotal to the process of arterial thrombosis resulting in ischemic stroke. Occlusive thrombosis is initiated by the interaction of von Willebrand factor (vWf) and platelet glycoprotein (GP) Ibalpha. Three polymorphisms have been described in GP Ibalpha (Kozak T/C polymorphism, variable number of tandem repeats [VNTR], and the human platelet antigen 2a [HPA-2a] [Thr] or HPA-2b [Met] at position 145), each of which may enhance the vWf and GP Ibalpha interaction. This study investigated whether these polymorphisms are candidate genes for first-ever ischemic stroke. A hospital-based case-control study was conducted of 219 cases of first-ever ischemic stroke and 205 community controls randomly selected from the electoral roll and stratified by age, sex, and postal code. The subtypes of stroke were classified, the prevalence of conventional risk factors was recorded, and blood was collected to perform genotyping analysis for Kozak C or T alleles, VNTR, and HPA-2a/b. It was found that the Kozak T/C genotype was over-represented in the stroke group (32.2%) compared with controls (22.8%) (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.03-2.54; P <.03), and the association was still present even after adjusting for conventional risk factors. There was a trend in the increased prevalence of HPA-2a/b in stroke patients (15%) compared with controls (9.9%) (adjusted OR, 1.8; 95% CI, 0.94-3.4; P =.07). No associations were seen with the VNTR polymorphism or with any of the polymorphisms with stroke subtype. It was concluded that the Kozak T/C polymorphism, which is associated with an increase in platelet GP Ibalpha surface expression, is an independent risk factor for first-ever ischemic stroke.

The Renalase Asp37Glu polymorphism is not associated with hypertension and cardiovascular events in an urban-based prospective cohort: the Malmö Diet and cancer study.

PubMed

Fava, Cristiano; Montagnana, Martina; Danese, Elisa; Sjögren, Marketa; Almgren, Peter; Engström, Gunnar; Hedblad, Bo; Guidi, Gian Cesare; Minuz, Pietro; Melander, Olle

2012-07-19

Renalase (gene name RNLS), a recently discovered enzyme with monoamine oxidase activity, is implicated in the degradation of catecholamines. Recent studies delineate a possible role of this enzyme in blood pressure (BP) maintenance and cardiac protection and two single nucleotide polymorphisms, RNLS rs2576178 A > G and rs2296545 C > G have been associated with hypertension. The latter SNP leads to a non synonymous Asp to Glu substitution deleting a flavin adenine dinucleotide (FAD) binding site with possible impaired functionality. We tested the hypothesis that these polymorphisms could affect BP levels, hypertension prevalence, and risk of incident cardiovascular events in middle-aged Swedes. The polymorphisms were genotyped in 5696 participants of the population-based Cardiovascular Cohort of the "Malmö Diet and Cancer" (MDC-CC). The incidence of cardiovascular events (coronary events [n = 408], strokes [n = 330], heart failure [n = 190] and atrial fibrillation/flutter [n = 406]) was monitored for an average of approximately 15 years of follow-up. Both before and after adjustment for sex, age and BMI the polymorphisms did not show any effect on BP level and hypertension prevalence. Before and after adjustment for major cardiovascular risk factors, the hazard ratio for cardiac and cerebrovascular events was not significantly different in carriers of different genotypes. A significant interaction was found between the rs2296545 C > G and age with respect to BP/hypertension. Our data do not support a major role for these RNLS polymorphisms in determining BP level and incident events at population level. The positive interaction with age suggest that the effect of the rs2296545 C > G polymorphism, if any, could vary between different ages.

Isolation and partial characterization of a root-specific promoter for stacking multiple traits into cassava (Manihot esculenta CRANTZ).

PubMed

Gbadegesin, M A; Beeching, J R

2011-06-07

Cassava can be cultivated on impoverished soils with minimum inputs, and its storage roots are a staple food for millions in Africa. However, these roots are low in bioavailable nutrients and in protein content, contain cyanogenic glycosides, and suffer from a very short post-harvest shelf-life, and the plant is susceptible to viral and bacterial diseases prevalent in Africa. The demand for improvement of cassava with respect to these traits comes from both farmers and national agricultural institutions. Genetic improvement of cassava cultivars by molecular biology techniques requires the availability of appropriate genes, a system to introduce these genes into cassava, and the use of suitable gene promoters. Cassava root-specific promoter for auxin-repressed protein was isolated using the gene walking approach, starting with a cDNA sequence. In silico analysis of promoter sequences revealed putative cis-acting regulatory elements, including root-specific elements, which may be required for gene expression in vascular tissues. Research on the activities of this promoter is continuing, with the development of plant expression cassettes for transformation into major African elite lines and farmers' preferred cassava cultivars to enable testing of tissue-specific expression patterns in the field.

Environmental exposure to arsenic, AS3MT polymorphism and prevalence of diabetes in Mexico

PubMed Central

Drobná, Zuzana; Del Razo, Luz M.; García-Vargas, Gonzalo G.; Sánchez-Peña, Luz C.; Barrera-Hernández, Angel; Stýblo, Miroslav; Loomis, Dana

2014-01-01

Exposure to arsenic in drinking water is associated with increased prevalence of diabetes. We previously reported an association of diabetes and urinary concentration of dimethylarsinite (DMAsIII), a toxic product of arsenic methylation by arsenic ( +3 oxidation state) methyltransferase (AS3MT). Here we examine associations between AS3MT polymorphism, arsenic metabolism and diabetes. Fasting blood glucose, oral glucose tolerance and self-reported diagnoses were used to identify diabetic individuals. Inorganic arsenic and its metabolites were measured in urine. Genotyping analysis focused on six polymorphic sites of AS3MT. Individuals with M287T and G4965C polymorphisms had higher levels of urinary DMAsIII and were more frequently diabetic than the respective wild-type carriers, although the excess was not statistically significant. Odds ratios were 11.4 (95% confidence interval (CI) 2.2–58.8) and 8.8 (95% CI 1.6–47.3) for the combined effects of arsenic exposure >75th percentile and 287T and 4965C genotypes, respectively. Carriers of 287T and 4965C may produce more DMAsIII and be more likely to develop diabetes when exposed to arsenic. PMID:23093101

Polymorphisms in exons 1B and 1C of the type I interleukin-1 receptor gene in patients with endometriosis.

PubMed

D'Amora, Paulo; Sato, Hélio; Girão, Manoel J B C; Silva, Ismael D C G; Schor, Eduardo

2006-09-01

To study possible correlation between the prevalence of polymorphisms in the type I interleukin-1 receptor gene and pelvic endometriosis. Genotypes of 223 women were analyzed: 109 women with surgically and histologically confirmed endometriosis and 114 healthy women. Distributions of two single-base polymorphisms of the human interleukin-1 receptor type I (IL-1RI) gene were evaluated: PstI, due to a C-->T transition in exon 1B and BsrBI a C-->A transition at position 52 in exon 1C. Polymorphisms were detected by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism analysis (RFLP) resolved on 3% agarose gels stained with ethidium bromide. Genotypes for PstI polymorphisms did not differ significantly among control and endometriosis (P = 0.058). However, in relation to BsrBI polymorphism, protective risk was observed for the development of endometriosis [OR 0.39-IC 95% (0.2-0.9)]. BsrBI heterozygote genotype (C/A) showed protective effect against endometriosis development.

Domestication syndrome in cassava (Manihot esculenta Crantz): Assessing morphological traits and differentially expressed genes associated with genetic diversity of storage root

USDA-ARS?s Scientific Manuscript database

Cassava is a starchy root crop that provides a staple food source for millions of people in tropical and subtropical regions of Asia, Latin America, and Africa. Brazil is considered the major center of diversification for species of the genus Manihot. It is also a center of domestication for the cul...

Prevalence of factor V leiden, MTHFR C677T and MTHFR A1298C polymorphisms in patients with deep vein thrombosis in Central Iran.

PubMed

Ehsani, Majid; Imani, Aida; Moravveji, Alireza

2018-05-31

Deep vein thrombosis (DVT) is a common disease, especially among elderly patients, which is associated with high costs of treatment and high rates of recurrence. The risk factors for venous thrombosis are primarily related to hypercoagulability, which can be genetic or acquired, or because of immobilization and venous stasis. Among relevant genetic markers are a number of common polymorphisms and mutations in the genes coding for Factor V leiden and methylenetetrahydrofolate reductase. Differential associations of these polymorphisms have been reported in different populations with DVT due to ethnic variations. However, no study has been reported with respect to these polymorphisms in DVT in Iran. Thus, the aim of the present study is to determine the prevalence of FVL, MTHFR C677T and MTHFR A1298C gene polymorphisms in patients with DVT in central Iran. In the present cross-sectional study, a total of 100 patients with first and recurrent episodes of DVT and age less than 70 years were recruited during 2016-2017. Blood sample was collected from the recruited patients and FVL mutation was screened using ARMS-PCR method, MTHFR C677T and MTHFR A1298C mutations were screened using PCR-RFLP method. The results revealed that MTHFR A1298C gene polymorphism in both homozygote and heterozygote form was found to be most frequent i.e. 77% among cases, followed by MTHFR C677T (67%) and FVL (17%). The study highlights the importance of screening of these genetic markers among patients with DVT in this region.

Factor XIII Val34Leu polymorphism and the risk of myocardial infarction under the age of 36 years.

PubMed

Rallidis, Loukianos S; Politou, Marianna; Komporozos, Christoforos; Panagiotakos, Demosthenes B; Belessi, Chrisoula I; Travlou, Anthi; Lekakis, John; Kremastinos, Dimitrios T

2008-06-01

There are limited and controversial data regarding the impact of factor XIII (FXIII) Val34Leu polymorphism in the pathogenesis of premature myocardial infarction (MI). We examined whether FXIII Val34Leu polymorphism is associated with the development of early MI. We recruited 159 consecutive patients who had survived their first acute MI under the age of 36 years (mean age = 32.1 +/- 3.6 years, 138 were men). The control group consisted of 121 healthy individuals matched with cases for age and sex, without a family history of premature coronary heart disease (CHD). FXIII Val34Leu polymorphism was tested with polymerase chain reaction and reverse hybridization. There was a lower prevalence of carriers of the Leu34 allele in patients than in controls (30.2 vs. 47.1%, p = 0.006). FXIII Val34Leu polymorphism was associated with lower risk for acute MI after adjusting for major cardiovascular risk factors (odds ratio [OR] = 0.51, 95% confidence interval [CI] 0.27-0.95, p = 0.03). Subgroup analysis according to angiographic findings ("normal" coronary arteries [n = 29] or significant CHD [n = 130]) showed that only patients with MI and significant CHD had lower prevalence of carriers of the Leu34 allele compared to controls after adjusting for major cardiovascular risk factors (OR = 0.42, 95% CI 0.22-0.83, p = 0.01). Our data indicate that FXIII Val34Leu polymorphism has a protective effect against the development of MI under the age of 36 years, particularly in the setting of significant CHD.

Lack of association of apolipoprotein E (Apo E) polymorphism with the prevalence of metabolic syndrome: the National Heart, Lung and Blood Institute Family Heart Study.

PubMed

Lai, Lana Y H; Petrone, Andrew B; Pankow, James S; Arnett, Donna K; North, Kari E; Ellison, R Curtis; Hunt, Steven C; Rosenzweig, James L; Djoussé, Luc

2015-09-01

Metabolic syndrome (MetS), characterized by abdominal obesity, atherogenic dyslipidaemia, elevated blood pressure and insulin resistance, is a major public health concern in the United States. The effects of apolipoprotein E (Apo E) polymorphism on MetS are not well established. We conducted a cross-sectional study consisting of 1551 participants from the National Heart, Lung and Blood Institute Family Heart Study to assess the relation of Apo E polymorphism with the prevalence of MetS. MetS was defined according to the American Heart Association-National Heart, Lung and Blood Institute-International Diabetes Federation-World Health Organization harmonized criteria. We used generalized estimating equations to estimate adjusted odds ratios (ORs) for prevalent MetS and the Bonferroni correction to account for multiple testing in the secondary analysis. Our study population had a mean age (standard deviation) of 56.5 (11.0) years, and 49.7% had MetS. There was no association between the Apo E genotypes and the MetS. The multivariable adjusted ORs (95% confidence interval) were 1.00 (reference), 1.26 (0.31-5.21), 0.89 (0.62-1.29), 1.13 (0.61-2.10), 1.13 (0.88-1.47) and 1.87 (0.91-3.85) for the Ɛ3/Ɛ3, Ɛ2/Ɛ2, Ɛ2/Ɛ3, Ɛ2/Ɛ4, Ɛ3/Ɛ4 and Ɛ4/Ɛ4 genotypes, respectively. In a secondary analysis, Ɛ2/Ɛ3 genotype was associated with 41% lower prevalence odds of low high-density lipoprotein [multivariable adjusted ORs (95% confidence interval) = 0.59 (0.36-0.95)] compared with Ɛ3/Ɛ3 genotype. Our findings do not support an association between Apo E polymorphism and MetS in a multicentre population-based study of predominantly White US men and women. Copyright © 2015 John Wiley & Sons, Ltd.

Leaf proteomic analysis in cassava (Manihot esculenta, Crantz) during plant development, from planting of stem cutting to storage root formation.

PubMed

Mitprasat, Mashamon; Roytrakul, Sittiruk; Jiemsup, Surasak; Boonseng, Opas; Yokthongwattana, Kittisak

2011-06-01

Tuberization in cassava (Manihot esculenta Crantz) occurs simultaneously with plant development, suggesting competition of photoassimilate partitioning between the shoot and the root organs. In potato, which is the most widely studied tuber crop, there is ample evidence suggesting that metabolism and regulatory processes in leaf may have an impact on tuber formation. To search for leaf proteins putatively involved in regulating tuber generation and/or development in cassava, comparative proteomic approaches have been applied to monitor differentially expressed leaf proteins during root transition from fibrous to tuberous. Stringent cross comparison and statistical analysis between two groups with different plant ages using Student's t test with 95% significance level revealed a number of protein spots whose abundance were significantly altered (P < 0.05) during week 4 to week 8 of growth. Of these, 39 spots were successfully identified by ion trap LC-MS/MS. The proteins span various functional categories from antioxidant and defense, carbohydrate metabolism, cyanogenesis, energy metabolism, miscellaneous and unknown proteins. Results suggested possible metabolic switches in the leaf that may trigger/regulate storage root initiation and growth. This study provides a basis for further functional characterization of differentially expressed leaf proteins, which can help understand how biochemical processes in cassava leaves may be involved in storage root development.

Genome-Wide Identification and Expression Analysis of the KUP Family under Abiotic Stress in Cassava (Manihot esculenta Crantz).

PubMed

Ou, Wenjun; Mao, Xiang; Huang, Chao; Tie, Weiwei; Yan, Yan; Ding, Zehong; Wu, Chunlai; Xia, Zhiqiang; Wang, Wenquan; Zhou, Shiyi; Li, Kaimian; Hu, Wei

2018-01-01

KT/HAK/KUP (KUP) family is responsible for potassium ion (K + ) transport, which plays a vital role in the response of plants to abiotic stress by maintaining osmotic balance. However, our understanding of the functions of the KUP family in the drought-resistant crop cassava ( Manihot esculenta Crantz) is limited. In the present study, 21 cassava KUP genes ( MeKUPs ) were identified and classified into four clusters based on phylogenetic relationships, conserved motifs, and gene structure analyses. Transcriptome analysis revealed the expression diversity of cassava KUPs in various tissues of three genotypes. Comparative transcriptome analysis showed that the activation of MeKUP genes by drought was more in roots than that in leaves of Arg7 and W14 genotypes, whereas less in roots than that in leaves of SC124 variety. These findings indicate that different cassava genotypes utilize various drought resistance mechanism mediated by KUP genes. Specific KUP genes showed broad upregulation after exposure to salt, osmotic, cold, H 2 O 2 , and abscisic acid (ABA) treatments. Taken together, this study provides insights into the KUP -mediated drought response of cassava at transcription levels and identifies candidate genes that may be utilized in improving crop tolerance to abiotic stress.

Productive potential of cassava plants (Manihot esculenta Crantz) propagated by leaf buds.

PubMed

Neves, Reizaluamar J; Diniz, Rafael P; Oliveira, Eder J DE

2018-04-23

New techniques of rapid multiplication of cassava (Manihot esculenta Crantz) have been developed, requiring technical support for large-scale use. This work main to evaluate the agronomic performance of plantlets obtained by leaf buds technique against stem cuttings in the field conditions. The work was conducted using the randomized block design in a factorial scheme with 3 varieties (BRS Kiriris, 98150-06, 9624-09) × 4 origins of the plantlets (conventional - stem cuttings of 20 cm length, leaf buds of the upper, middle and inferior stem part) × 2 agrochemicals (control and treated). There was a remarkable decrease in some agronomic traits that ranged from 23% (number of branches) to 62% (shoot weight) when using leaf buds plantlets. The treatment of plantlets with agrochemicals promoted significant increases in all traits, ranging from 26% (number of roots per plant) to 46% (shoot weight). The plantlets originating from leaf buds of the upper and middle parts were able to generate stem-like plants similar to stem-derived ones. Despite its lower agronomic performance under field conditions, multiplication by leaf buds may generate five times the number of propagules in comparison with the conventional multiplication, and therefore it could be a viable alternative for rapid cassava multiplication.

Neurotoxic effect of linamarin in rats associated with cassava (Manihot esculenta Crantz) consumption.

PubMed

Rivadeneyra-Domínguez, Eduardo; Vázquez-Luna, Alma; Rodríguez-Landa, Juan Francisco; Díaz-Sobac, Rafael

2013-09-01

Cassava (Manihot esculenta Crantz) is a plant widely used for food consumption in different processed products in rural areas of Africa, Asia, and Latin America. Cassava is a good source of carbohydrates and micronutrients. However, if it is not adequately processed or the consumer has nutritional deficiencies, then its cyanogenic glycoside (i.e., linamarin and lotaustralin) content makes it potentially neurotoxic. In the present study, the neurotoxic effects of different concentrations of linamarin (0.075, 0.15, 0.22, and 0.30 mg/kg) contained in cassava juice were evaluated in the open field and swim tests to identify locomotor alterations in adult male Wistar rats. The linamarin concentration in cassava juice was determined by high-performance liquid chromatography, and the juice was administered intraesophageally for 28 days. The results suggested that the consumption of linamarin in cassava juice increased the number of crossings and rearings in the open field test and caused behavioral deficiency, reflected by lateral swimming, in the swim test on days 21 and 28 of treatment. These alterations are possibly related to neuronal damage caused by linamarin in cassava juice in structures of the central nervous system involved in motor processing. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cassava (Manihot esculenta Crantz) and Yam (Dioscorea spp.) Crops and Their Derived Foodstuffs: Safety, Security and Nutritional Value.

PubMed

Ferraro, Vincenza; Piccirillo, Clara; Tomlins, Keith; Pintado, Manuela E

2016-12-09

Cassava (Manihot esculenta Crantz) and yam (Dioscorea spp.) are tropical crops consumed by ca. 2 billion people and represent the main source of carbohydrate and energy for the approximately 700 million people living in the tropical and sub-tropical areas. They are a guarantee of food security for developing countries. The production of these crops and the transformation into food-derived commodities is increasing, it represents a profitable business and farmers generate substantial income from their market. However, there are some important concerns related to the food safety and food security. The high post-harvest losses, mainly for yam, the contamination by endogenous toxic compounds, mainly for cassava, and the contamination by external agents (such as micotoxins, pesticides, and heavy metal) represent a depletion of economic value and income. The loss in the raw crops or the impossibility to market the derived foodstuffs, due to incompliance with food regulations, can seriously limit all yam tubers and the cassava roots processors, from farmers to household, from small-medium to large enterprises. One of the greatest challenges to overcome those concerns is the transformation of traditional or indigenous processing methods into modern industrial operations, from the crop storage to the adequate package of each derived foodstuff.

Differential distribution and association of FTO rs9939609 gene polymorphism with obesity: A cross-sectional study among two tribal populations of India with East-Asian ancestry.

PubMed

Ningombam, Somorjit Singh; Chhungi, Varhlun; Newmei, Masan Kambo; Rajkumari, Sunanda; Devi, Naorem Kiranmala; Mondal, Prakash Ranjan; Saraswathy, Kallur Nava

2018-03-20

The fat mass and obesity associated (FTO) rs9939609 gene polymorphism is most widely studied in terms of obesity in various populations. Recently, the prevalence of obesity has been reported to be very high among the North-Eastern State of India. The major aim of the present study is to understand the extent of FTO rs9939609 gene polymorphism and its association with obesity among the two North-East Indian tribal populations with similar East Asian ancestry. Somatometric data and fasting blood sample were collected from 521 tribal individuals (258 Liangmai and 263 Mizo) of Manipur after obtaining written informed consent. Genotyping of FTO rs9939609 single nucleotide polymorphism (SNP) was done using restriction fragment length polymorphism method for PCR-amplified fragments. Both the presently studied populations were not following Hardy-Weinberg law. The prevalence of obesity and minor allele frequency of FTO rs9939609 polymorphism was found to be significantly higher among the Mizo tribe compared to that of Liangmai. The selected polymorphism was found to be significantly associated with obesity (BMI) only among the Liangmai tribe (Odds ratio-3.0; 95% CI-1.4, 6.4; p-0.003), after adjusting for age and occupation. Age-cohort wise distribution and absolute fitness analysis indicated the lower fitness of minor allele in the higher age group among the Liangmai tribe. To the best of the author's knowledge this is the first study, associating FTO rs9939609 gene polymorphism and obesity in the North-eastern Indian tribal populations with East-Asian ancestry. This study revealed the FTO rs9939609 polymorphism is observed to be associated with obesity only among the Liangmai tribe not among the Mizo tribe. The differential distribution and association observed in the two selected tribes, inhabited in a similar geographical region, could be attributed to differences in their migratory histories in terms of both route and time of settlement. Copyright © 2018 Elsevier B.V. All rights reserved.

Association between Interleukin-10-1082 G/A and Tumor Necrosis Factor-α 308 G/A Gene Polymorphisms and Respiratory Distress Syndrome in Iranian Preterm Infants.

PubMed

Khoshdel, Abolfazl; Kheiri, Soleiman; Omidvari, Peyman; Moradi, Fahimeh; Hamidi, Majid; Teimori, Hossein

2017-01-01

Cytokine polymorphisms may contribute to the prevalence of respiratory distress syndrome. The present study was done to investigate the frequency of interleukin- (IL-) 10 and tumor necrosis factor- (TNF-) α gene polymorphisms and their association with the risk of RDS in preterm infants. One-hundred and nineteen patients with RDS and 119 healthy preterm infants were enrolled. PCR restriction fragment length polymorphism was used to determine the frequency of IL-10 and TNF- α genotypes at -1082 A and -308 A, respectively. One-hundred and nineteen out of 238 infants had RDS (50%). The age of the mothers and gestational age ranged 17-45 (mean: 28.6 ± 5.3) years and 24-34 (mean: 34.3 ± 2.38) weeks, respectively. Totally, 23 deaths were recorded in the RDS group. Incidence of TNF- α -308 A/A and TNF- α -308 G/A was 84% and 16%, respectively. TNF-a-308 G/G was not found in both groups. Prevalence of IL-10-1082 G/G and IL-10-1082 G/A variants was 65.5% and 34.5%, respectively. IL-10-1082 A/A was not found in both groups. The incidence of the allele G in the IL-10-1082 polymorphism was lower in RDS group ( P < 0.05). We found that the risk of RDS was correlated to sex, gestational age, and IL-10-1082.

Association between Interleukin-10-1082 G/A and Tumor Necrosis Factor-α 308 G/A Gene Polymorphisms and Respiratory Distress Syndrome in Iranian Preterm Infants

PubMed Central

Omidvari, Peyman; Moradi, Fahimeh; Hamidi, Majid; Teimori, Hossein

2017-01-01

Cytokine polymorphisms may contribute to the prevalence of respiratory distress syndrome. The present study was done to investigate the frequency of interleukin- (IL-) 10 and tumor necrosis factor- (TNF-) α gene polymorphisms and their association with the risk of RDS in preterm infants. One-hundred and nineteen patients with RDS and 119 healthy preterm infants were enrolled. PCR restriction fragment length polymorphism was used to determine the frequency of IL-10 and TNF-α genotypes at -1082 A and -308 A, respectively. One-hundred and nineteen out of 238 infants had RDS (50%). The age of the mothers and gestational age ranged 17–45 (mean: 28.6 ± 5.3) years and 24–34 (mean: 34.3 ± 2.38) weeks, respectively. Totally, 23 deaths were recorded in the RDS group. Incidence of TNF-α-308 A/A and TNF-α-308 G/A was 84% and 16%, respectively. TNF-a-308 G/G was not found in both groups. Prevalence of IL-10-1082 G/G and IL-10-1082 G/A variants was 65.5% and 34.5%, respectively. IL-10-1082 A/A was not found in both groups. The incidence of the allele G in the IL-10-1082 polymorphism was lower in RDS group (P < 0.05). We found that the risk of RDS was correlated to sex, gestational age, and IL-10-1082. PMID:28298812

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.

Polymorphisms in NOS3, MTHFR, APOB and TNF-α Genes and Risk of Coronary Atherosclerotic Lesions in Iranian Patients

PubMed Central

Heidari, Mohammad Mehdi; Khatami, Mehri; Hadadzadeh, Mehdi; Kazemi, Mahbobeh; Mahamed, Sahar; Malekzadeh, Pegah; Mirjalili, Massomeh

2015-01-01

Background: Atherosclerosis is a complex multifocal arterial disease involving interactions between multiple genetic and environmental factors. Objectives: In the present study, we investigated the possible association between NOS3 (rs1799983), MTHFR (rs1801133), APOB (rs5742904) and TNF-α (rs361525) polymorphisms and the risk of coronary atherosclerotic lesions in Iranian patients. Patients and Methods: In the case-control study, 108 patients with coronary atherosclerosis disease and 95 control subjects with no family history of cardiovascular disease were enrolled. Genotypes for NOS3, MTHFR, APOB and TNF-α polymorphisms were identified using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Results: We specifically detected the NOS3 TT genotype in 12 patients (11.11%) and did not find the same genotype in any of the controls. The frequencies of T allele in patients and the controls were 24% and 17.8%, respectively. The prevalence of the MTHFR TT genotype was 16.7% in patients and 2.2% in control groups. The prevalence of the APOB-100 (R3500Q) mutation in this patient population was 0%. The frequency of the A allele in the TNF-α gene was 11.1% and 11% in patients and controls, respectively, and the AA genotype was undetected. Conclusions: Our results show a significant association of NOS3 and MTHFR gene polymorphisms with coronary atherosclerotic lesions. Therefore, these variants might influence the risk of coronary artery disease, specifically in the Iranian population. PMID:26878010

The Effect of ABO Blood Groups, Hemoglobinopathy, and Heme Oxygenase-1 Polymorphisms on Malaria Susceptibility and Severity.

PubMed

Kuesap, Jiraporn; Na-Bangchang, Kesara

2018-04-01

Malaria is one of the most important public health problems in tropical areas on the globe. Several factors are associated with susceptibility to malaria and disease severity, including innate immunity such as blood group, hemoglobinopathy, and heme oxygenase-1 (HO-1) polymorphisms. This study was carried out to investigate association among ABO blood group, thalassemia types and HO-1 polymorphisms in malaria. The malarial blood samples were collected from patients along the Thai-Myanmar border. Determination of ABO blood group, thalassemia variants, and HO-1 polymorphisms were performed using agglutination test, low pressure liquid chromatography and polymerase chain reaction, respectively. Plasmodium vivax was the major infected malaria species in the study samples. Distribution of ABO blood type in the malaria-infected samples was similar to that in healthy subjects, of which blood type O being most prevalent. Association between blood group A and decreased risk of severe malaria was significant. Six thalassemia types (30%) were detected, i.e. , hemoglobin E (HbE), β-thalassemia, α-thalassemia 1, α-thalassemia 2, HbE with α-thalassemia 2, and β-thalassemia with α-thalassemia 2. Malaria infected samples without thalassemia showed significantly higher risk to severe malaria. The prevalence of HO-1 polymorphisms, S/S, S/L and L/L were 25, 62, and 13%, respectively. Further study with larger sample size is required to confirm the impact of these 3 host genetic factors in malaria patients.

Polymorphisms associated with resistance to protease inhibitors in naïve patients infected with hepatitis C virus genotype 1 in Argentina: Low prevalence of Q80K.

PubMed

Martínez, Alfredo P; Culasso, Andrés C A; Pérez, Paula S; Romano, Vanesa; Campos, Rodolfo H; Ridruejo, Ezequiel; García, Gabriel; Di Lello, Federico A

2017-08-15

Incorporation of direct acting antivirals (DAA) in the treatment of Hepatitis C Virus (HCV) significantly increases sustained virologic response rates. However, despite the greater potency offered by these antivirals, drug resistance plays a key role in patients with failure to DAA. Nevertheless, there is no information about the prevalence of resistance-associated substitutions (RASs) in Argentina. The aim of this study was to analyze HCV variants resistant to protease inhibitors (PI) in naïve patients infected with HCV genotype 1 from Argentina. In this retrospective cross-sectional study, 103 patients infected with HCV-1 were included. Eighteen positions related with RASs were analyzed by Sanger at baseline and phylogenetic analysis was performed to determine the diversification of this samples. The analyzed RASs were present in 38 out of 103 patients (36.9%) infected with HCV-1. Patients infected with subtype HCV-1b had higher prevalence of baseline RASs than patients infected with HCV-1a [51.6% vs. 12.8%, respectively (p<0.001)]. The Q80K polymorphism was not found in HCV-1a samples, even when 51% of them belonged to cluster 1, which is associated with a high frequency of Q80K. Phylogenetic analysis showed that Argentinean samples were intermingled with sequences from other geographic regions. RASs to PI were highly prevalent and subtype dependent in treatment-naïve Argentinean patients. Surprisingly, Q80K polymorphism was not detected in our study population. The phylogenetic analysis showed no relationship between our samples and other samples from Brazil which also present a low prevalence of Q80K. This study supports the need for surveillance of resistance in patients who will be treated with DAA in each particular country since the observed RASs have very different prevalence worldwide. Copyright © 2017 Elsevier B.V. All rights reserved.

Glutathione S-transferase gene polymorphisms (GSTM1, GSTT1, and GSTP1) in Egyptian pediatric patients with sickle cell disease.

PubMed

Shiba, Hala Fathy; El-Ghamrawy, Mona Kamal; Shaheen, Iman Abd El-Mohsen; Ali, Rasha Abd El-Ghani; Mousa, Somaia Mohammed

2014-01-01

Sickle cell disease (SCD) complications are associated with oxidative stress. Glutathione S-transferases (GSTs) are a group of enzymes that protect against oxidative stress. The aims of this study was to evaluate the prevalence of GSTM1, GSTT1, and GSTP1 gene polymorphisms among homozygous sickle cell anemia patients and to investigate the possible association between the presence of these polymorphisms and SCD severity and complications. Genotyping the polymorphisms in GSTT1 and GSTM1 genes was performed using the multiplex polymerase chain reaction (PCR) method. The GSTP1 ILe105Val polymorphism was determined using PCR-restriction fragment length polymorphism. GSTM1 null genotype was significantly associated with increased risk of severe vaso-occlusive crises (VOC) (odds ratio  =  1.52, 95% confidence interval  =  0.42-5.56, P  =  0.005). We found no significant association between GST genotypes and frequency of sickle cell-related pain, transfusion frequency, disease severity, or hydroxyurea treatment. GSTM1 gene polymorphism may be associated with risk of severe VOC among Egyptian SCD patients.

Investigation on the association between NLRP3 gene polymorphisms and susceptibility to primary gout.

PubMed

Wang, L F; Ding, Y J; Zhao, Q; Zhang, X L

2015-12-09

We conducted a case-control study to investigate the association between 3 common NALP3 polymorphisms (rs10754558, rs7512998, and rs12137901) and the susceptibility to primary gout. A total of 320 patients with primary gout and 320 controls were included in this study. The genotyping of NALP3 rs10754558, rs7512998, and rs12137901 were conducted by polymerase chain reaction-restriction fragment length polymorphism. Comparison analysis showed that primary gout patients were more likely to have higher body mass index, prevalence of hypertension, blood glucose, triglycerides, urea nitrogen, and uric acid (P < 0.05). Logistic regression analysis revealed no significant association between the NALP3 rs10754558, rs7512998, and rs12137901 polymorphisms and the risk of gouty arthritis. In conclusion, we found no significant association between NALP3 gene polymorphisms and the risk of primary gout.

Frequency of mutations in PROP-1 gene in Turkish children with combined pituitary hormone deficiency.

PubMed

Kandemir, Nurgün; Vurallı, Doğuş; Taşkıran, Ekim; Gönç, Nazlı; Özön, Alev; Alikaşifoğlu, Ayfer; Yılmaz, Engin

2012-01-01

Mutations in the prophet of Pit-1 (PROP-1) gene are responsible for most of the cases of combined pituitary hormone deficiencies (CPHD). We performed this study to determine the prevalence of PROP-1 mutations in a group of Turkish children with CPHD. Fifty-three children with the diagnosis of CPHD were included in this study. Clinical data were obtained from medical files, and hormonal evaluation and genetic screening for PROP-1 mutations were performed. A homozygous S109X mutation was found in the second exon in two brothers, and they had growth hormone (GH) and thyroid-stimulating hormone (TSH) deficiencies and normal prolactin levels. In the third exon of the PROP-1 gene, a heterozygous A142T polymorphism was found in 14 patients and a homozygous A142T polymorphism was found in 3 patients. In the first exon, a homozygous A9A polymorphism was found in 7 patients and a heterozygous A9A polymorphism was found in 31 patients. We assumed that mutations in the PROP-1 gene in cases with CPHD were expected to be more prevalent in our population due to consanguinity, but it was found that these mutations were far less than expected and that it was rare in non-familial cases.

Fas and FasL genetic polymorphisms in women with recurrent pregnancy loss: a case-control study.

PubMed

Han, Ae Ra; Choi, Young Min; Hong, Min A; Kim, Jin Ju; Lee, Sung Ki; Yang, Kwang Moon; Paik, Eun Chan; Jeong, Hyeon Jeong; Jun, Jong Kwan

2018-05-20

Aberrant apoptosis at the trophoblast-maternal interface and abnormal expression of Fas and Fas ligand (FasL) have been reported in complicated pregnancies with recurrent pregnancy losses (RPL) and preeclampsia. We assessed the prevalence of Fas and FasL genetic polymorphisms in Korean women with RPL and in fertile controls. In total, 306 women with RPL and 298 fertile controls were enrolled. Genotype distributions of Fas and FasL in RPL patients versus fertile controls were examined under the Hardy-Weinberg equilibrium. Fas -670 A/G genotype (AA versus AG versus GG, p = 0.340) and allele frequencies (A versus G, p = 0.412) were not different between the RPL and control groups. There was no difference in each Fas -1377 G/A and FasL -844 C/T genotype, and their allele frequencies. In addition, the unions of two zygosities of each genotype and their combined genotypes did not differ between two groups. No difference in the prevalence of Fas and FasL single-nucleotide polymorphisms (SNPs) was observed between women with RPL and fertile controls among Korean women. To determine the possibility of genetic polymorphisms in Fas and its ligand as risk factors for RPL, further studies in various races and a large study population are needed.

K13-Propeller Polymorphisms in Plasmodium falciparum Parasites From Sub-Saharan Africa

PubMed Central

Kamau, Edwin; Campino, Susana; Amenga-Etego, Lucas; Drury, Eleanor; Ishengoma, Deus; Johnson, Kimberly; Mumba, Dieudonne; Kekre, Mihir; Yavo, William; Mead, Daniel; Bouyou-Akotet, Marielle; Apinjoh, Tobias; Golassa, Lemu; Randrianarivelojosia, Milijaona; Andagalu, Ben; Maiga-Ascofare, Oumou; Amambua-Ngwa, Alfred; Tindana, Paulina; Ghansah, Anita; MacInnis, Bronwyn; Kwiatkowski, Dominic; Djimde, Abdoulaye A.

2015-01-01

Mutations in the Plasmodium falciparum K13-propeller domain have recently been shown to be important determinants of artemisinin resistance in Southeast Asia. This study investigated the prevalence of K13-propeller polymorphisms across sub-Saharan Africa. A total of 1212 P. falciparum samples collected from 12 countries were sequenced. None of the K13-propeller mutations previously reported in Southeast Asia were found, but 22 unique mutations were detected, of which 7 were nonsynonymous. Allele frequencies ranged between 1% and 3%. Three mutations were observed in >1 country, and the A578S was present in parasites from 5 countries. This study provides the baseline prevalence of K13-propeller mutations in sub-Saharan Africa. PMID:25367300

Study of the role of tumor necrosis factor-α (-308 G/A) and interleukin-10 (-1082 G/A) polymorphisms as potential risk factors to acute kidney injury in patients with severe sepsis using high-resolution melting curve analysis.

PubMed

Hashad, Doaa I; Elsayed, Eman T; Helmy, Tamer A; Elawady, Samier M

2017-11-01

Septic acute kidney injury (AKI) is a prevalent complication in intensive care units with an increased incidence of complications. The aim of the present study was to assess the use of high-resolution melting curve (HRM) analysis in investigating whether the genetic polymorphisms; -308 G/A of tumor necrosis factor-α (TNF-α), and -1082 G /A of Interleukin-10 (IL-10) genes may predispose patients diagnosed with severe sepsis to the development of AKI. One hundred and fifty patients with severe sepsis participated in the present study; only sixty-six developed AKI. Both polymorphisms were studied using HRM analysis. The low producer genotype of both studied polymorphism of TNF-α and IL-10 genes was associated with AKI. Using logistic regression analysis, the low producer genotypes remained an independent risk factor for AKI. A statistically significant difference was detected between both studied groups as regards the low producer genotype in both TNF-α (-308 G/A) and interleukin-10 (IL-10) (-1082 G/A) polymorphisms being prevalent in patients developing AKI. Principle conclusions: The low producer genotypes of both TNF-α (-308 G/A) and IL-10 (-1082 G/A) polymorphisms could be considered a risk factor for the development of AKI in critically ill patients with severe sepsis, thus management technique implemented for this category should be modulated rescuing this sector of patients from the grave deterioration to acute kidney injury. Using HRM for genotyping proved to be a highly efficient, simple, cost-effective genotyping technique that is most appropriate for the routine study of large-scale samples.

Evaluation of ERα and VDR gene polymorphisms in relation to bone mineral density in Turkish postmenopausal women.

PubMed

Kurt, Ozlem; Yilmaz-Aydogan, Hulya; Uyar, Mehmet; Isbir, Turgay; Seyhan, Mehmet Fatih; Can, Ayse

2012-06-01

It has been suggested that the estrogen receptor alpha (ERα) and vitamin D receptor (VDR) genes as possibly implicated in reduced bone mineral density (BMD) in osteoporosis. The present study investigated the relation of ERα PvuII/XbaI polymorphisms and VDR FokI/TaqI polymorphisms with BMD in Turkish postmenopausal women. Eighty-one osteoporotic and 122 osteopenic postmenopausal women were recruited. For detection of the polymorphisms, polymerase chain reaction-restriction fragment lenght polymorphism techniques have been used. BMD was measured at the lumbar spine and hip by dual-energy X-ray absorptiometry. Distributions of ERα (PvuII dbSNP: rs2234693, XbaI dbSNP: rs9340799) and VDR genotypes (FokI dbSNP rs10735810, TaqI dbSNP: rs731236) were similar in study population. Although overall prevalence of osteoporosis had no association with these genotypes, the prevalence of decreased femoral neck BMD values were higher in the subjects with ERα PvuII "PP" and ERα XbaI "XX" genotypes than in those with "Pp/pp" genotypes and "xx" genotype, respectively (P < 0.05). Furthermore, subjects with VDR FokI "FF" genotype had lower BMD values of femoral neck and total hip compared to those with "Ff" genotype (P < 0.05). In the logistic regression analysis, we confirmed the presence of relationships between the VDR FokI "FF" genotypes, BMI ≤ 27.5, age ≥ 55 and the increased risk of femoral neck BMD below 0.8 value in postmenopausal women. The present data suggests that the ERα PvuII/XbaI and VDR FokI polymorphisms may contribute to the determination of bone mineral density in Turkish postmenopausal women.

High frequency of Neuropeptide Y Leu7Pro polymorphism in an Iranian population and its association with coronary artery disease.

PubMed

Masoudi-Kazemabad, Ali; Jamialahmadi, Khadijeh; Moohebati, Mohsen; Mojarrad, Majid; Dehghan-Manshadi, Raheleh; Forghanifard, Mohammad Mahdi; Akhlaghi, Saeed; Ferns, Gordon A; Ghayour-Mobarhan, Majid

2012-03-15

Neuropeptide Y (NPY), a 36-amino acid peptide, is widely expressed in the central and peripheral nervous systems as well as in the heart. A relationship has been reported between NPY gene variants and coronary artery disease (CAD) in some populations. However, there are few data on the NPY gene polymorphism and CAD in the Persian population. In the current study we have investigated the relationship between the NPY Leu7Pro polymorphism and CAD within a population from Iran. A total of 1061 subjects were recruited; 609 patients and 452 healthy subjects. Four hundred and twenty eight of the patients had >50% stenosis; with the remaining 181 patients having <50% stenosis based on angiography. Angiography positive patients were divided into three groups: those with single (n=115), double (n=140), and triple vessel (n=173) disease. DNA analysis for the Leu7Pro polymorphism was performed using a PCR-RFLP technique. A significantly higher frequency of the Leu7Pro genotype was observed in CAD patients compared with the control group (P<0.05). Patients with the Pro7 had significantly higher values for weight (P=0.027), BMI (P=0.001), hip circumference (P=0.003) and prevalence of diabetes mellitus (P=0.018) but reduced prevalence of a history of myocardial infarction (P=0.017). The frequency of Leu7Pro polymorphism of NPY was 5.9% in our Iranian population; higher than reported for other Asian populations. The Leu7Pro polymorphism was associated with CAD in an Iranian population. Copyright © 2012 Elsevier B.V. All rights reserved.

Unexpected selections of Plasmodium falciparum polymorphisms in previously treatment-naïve areas after monthly presumptive administration of three different anti-malarial drugs in Liberia 1976-78.

PubMed

Jovel, Irina T; Björkman, Anders; Roper, Cally; Mårtensson, Andreas; Ursing, Johan

2017-03-13

To assess the effect on malaria prevalence, village specific monthly administrations of pyrimethamine, chlorproguanil, chloroquine or placebo were given to children in four previously treatment-naïve Liberian villages, 1976-78. Plasmodium falciparum in vivo resistance developed to pyrimethamine only. Selection of molecular markers of P. falciparum resistance after 2 years of treatment are reported. Blood samples were collected from 191 study children in a survey in 1978. Polymorphisms in pfcrt, pfmdr1, pfdhfr, pfdhps, pfmrp1 and pfnhe1 genes were determined using PCR-based methods. Pfcrt 72-76 CVIET was found in one chloroquine village sample, all remaining samples had pfcrt CVMNK. Pfmdr1 N86 prevalence was 100%. A pfmdr1 T1069 ACT→ACG synonymous polymorphism was found in 30% of chloroquine village samples and 3% of other samples (P = 0.008). Variations in pfnhe1 block I were found in all except the chloroquine treated village (P < 0.001). Resistance associated pfdhfr 108N prevalence was 2% in the pyrimethamine village compared to 45-65% elsewhere, including the placebo village (P = 0.001). Chloroquine treatment possibly resulted in the development of pfcrt 72-76 CVIET. Selection of pfmdr1 T1069 ACG and a pfnhe1 block 1 genotypes indicates that chloroquine treatment exerted a selective pressure on P. falciparum. Pyrimethamine resistance associated pfdhfr 108N was present prior to the introduction of any drug. Decreased pfdhfr 108N frequency concurrent with development of pyrimethamine resistance suggests a non-pfdhfr polymorphisms mediated resistance mechanism.

A gene-environment interaction analysis of plasma selenium with prevalent and incident diabetes: The Hortega study.

PubMed

Galan-Chilet, Inmaculada; Grau-Perez, Maria; De Marco, Griselda; Guallar, Eliseo; Martin-Escudero, Juan Carlos; Dominguez-Lucas, Alejandro; Gonzalez-Manzano, Isabel; Lopez-Izquierdo, Raul; Briongos-Figuero, Laisa Socorro; Redon, Josep; Chaves, Felipe Javier; Tellez-Plaza, Maria

2017-08-01

Selenium and single-nucleotide-polymorphisms in selenoprotein genes have been associated to diabetes. However, the interaction of selenium with genetic variation in diabetes and oxidative stress-related genes has not been evaluated as a potential determinant of diabetes risk. We evaluated the cross-sectional and prospective associations of plasma selenium concentrations with type 2 diabetes, and the interaction of selenium concentrations with genetic variation in candidate polymorphisms, in a representative sample of 1452 men and women aged 18-85 years from Spain. The geometric mean of plasma selenium levels in the study sample was 84.2µg/L. 120 participants had diabetes at baseline. Among diabetes-free participants who were not lost during the follow-up (N=1234), 75 developed diabetes over time. The multivariable adjusted odds ratios (95% confidence interval) for diabetes prevalence comparing the second and third to the first tertiles of plasma selenium levels were 1.80 (1.03, 3.14) and 1.97 (1.14, 3.41), respectively. The corresponding hazard ratios (95% CI) for diabetes incidence were 1.76 (0.96, 3.22) and 1.80 (0.98, 3.31), respectively. In addition, we observed significant interactions between selenium and polymorphisms in PPARGC1A, and in genes encoding mitochondrial proteins, such as BCS1L and SDHA, and suggestive interactions of selenium with other genes related to selenoproteins and redox metabolism. Plasma selenium was positively associated with prevalent and incident diabetes. While the statistical interactions of selenium with polymorphisms involved in regulation of redox and insulin signaling pathways provide biological plausibility to the positive associations of selenium with diabetes, further research is needed to elucidate the causal pathways underlying these associations. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Low bone mineral density and vitamin d deficiency correlated with genetics and other bone markers in female Turkish immigrants in Germany.

PubMed

Tastan, Yasemin; Kann, Peter Herbert; Tinneberg, Hans-Rudolf; Hadji, Peyman; Müller-Ladner, Ulf; Lange, Uwe

2016-11-01

Patients with osteoporosis have a low bone mass resulting in an increased risk for bone fractures, morbidity and mortality. One hundred thirty-one female pre-menopausal participants (98 Turkish immigrants living in Germany in comparison with 33 age-matched healthy Germans) were recruited for this study which explored vitamin D deficiency and specific genetic modifications of bone metabolism. The subjects were investigated for their femoral and lumbar bone mineral density (BMD) by dual-energy X-ray absorptiometry (DEXA) of the right total femur and the lumbar spine. Serum levels of osteologic parameters were determined: parathormone (PTH), calcium (Ca), osteocalcin (OC), phosphate (P), alkaline phosphatase (AP), beta-crossLaps (CL), tartrate-resistant acid phosphatase isoform 5b (TRAP5b), and 25-vitamin D 3 (25-OH D 3 ). The Bsml- and Fokl-polymorphisms of the vitamin D receptor (VDR) gene and the collagen type I alpha 1 (COLIA1)-gene polymorphism were also genotyped. An extremely high prevalence of vitamin D deficiency could be found in the immigrant cohort (87.8 %). Osteoporosis but not osteopenia was more prevalent in this group. Among immigrants with osteoporosis, TRAP5b was elevated in 42.9 % and beta-CL in 28.6 %. Only the Fokl FF-genotype of the VDR polymorphism was significantly more prevalent among the Turkish women, Ff-genotyped immigrants showed significantly decreased BMD. A significant correlation between the COLIA1-gene polymorphism and BMD could not be identified in the two groups. Vitamin D deficiency and osteoporosis appear to be dominant and unrecognized problem among female Turkish immigrants in Germany. Therefore, in this population, osteologic parameters and BMD should be routinely analyzed and deficiencies be treated immediately.

High prevalence of natural polymorphisms in Gag (CA-SP1) associated with reduced response to Bevirimat, an HIV-1 maturation inhibitor.

PubMed

Seclén, Eduardo; González, María Del Mar; Corral, Angélica; de Mendoza, Carmen; Soriano, Vincent; Poveda, Eva

2010-01-28

Mutations H358Y, L363F/M, A364V and A366T/V confer in-vitro resistance to bevirimat. Moreover, polymorphisms at the Glutamine-Valine-Threonine (QVT) motif (369-371) have been associated with reduced bevirimat activity in vivo. The rate of these changes was assessed in 389 HIV+ patients naïve for bevirimat. QVT polymorphisms were frequent (47%), especially in non-B subtypes (93%). Conversely, only four patients (1%) harbored major bevirimat resistance mutations. Finally, specific gag changes were associated with protease inhibitor resistance mutations in subtype B viruses.

Genetic Polymorphisms of Cytochrome P450 Enzymes and Transport Proteins in a Russian Population and Three Ethnic Groups of Dagestan.

PubMed

Mirzaev, Karin B; Sychev, Dmitry A; Ryzhikova, Kristina A; Konova, Olga D; Mammaev, Suleiman N; Gafurov, Daniyal M; Shuev, Grigorij N; Grishina, Elena A; Sozaeva, Zhannet A

2017-12-01

The objective of this study was to investigate the prevalence of polymorphic markers of the CYP2C19, CYP2C9, CYP2D6, SLCO1B1, and ABCB1 genes among the three ethnic groups in Dagestan and compare it with the carrier frequency of these markers among the Russian population living in Moscow. The study involved 186 healthy, unrelated, and chronic medication-free volunteers (53 males and 133 females) of the three ethnic groups in the Dagestan Republic: 46 Laks, 90 Avars, and 50 Dargins. Genotyping was performed using real-time polymerase chain reaction-based methods. The allelic prevalences of the three Dagestan peoples were compared with ethnic Russians from the Moscow region. Statistically significant differences for the following gene polymorphisms: CYP2C19*17, CYP2C9*3, ABCB1 (C3435T), SLCO1B1*5 were found between the Russian population and the three ethnic groups of the Dagestan republic. The data obtained from this study will help with prioritization genotyping in the region.

Heterologous co-expression in E. coli of isoamylase genes from cassava Manihot esculenta Crantz 'KU50' achieves enzyme-active heteromeric complex formation.

PubMed

Panpetch, Pawinee; Field, Robert A; Limpaseni, Tipaporn

2018-03-01

Cloning of two isoamylase genes, MeISA1 and MeISA2, from cassava (Manihot esculenta Crantz) tubers, accompanied by their co-expression in E. coli demonstrates a requirement for heteromeric complex formation to achieve debranching activity. Starch debranching enzyme (DBE) or isoamylase (ISA) (EC.3.2.1.68), an important enzyme in starch metabolism, catalyses the hydrolysis of α-1,6 glycosidic linkages of amylopectin. Isoforms of ISAs have been reported in higher plants and algae (Fujita et al. in Planta 208:283-293, 1999; Hussain et al. in Plant Cell 15:133-149, 2003; Ishizaki et al. in Agric Biol Chem 47:771-779, 1983; Mouille et al. in Plant Cell 8:1353-1366, 1996). In the current work, cassava ISA genes were isolated from cDNA generated from total RNA from tubers of Manihot esculanta Crantz cultivar KU50. MeISA1 and MeISA2 were successfully amplified and cloned into a pETDuet1 vector. The putative MeISA1 and MeISA2 proteins comprised 763 and 882 amino acids, with substantial similarity to StISA1 and StISA2 from potato (84.4% and 68.9%, respectively). Recombinant MeISA1 and MeISA2 were co-expressed in Escherichia coli SoluBL21 (DE3). Histrap TM -Purified rMeISA1 and rMeISA2 showed approximate molecular weights of 87 and 99 kDa, respectively, by SDS-PAGE. Debranching activity was only detectable in the column fractions where both recombinant ISA isoforms were present. The heteromeric DBE from crude extracts of 4-5 h induced cultures analysed by gel filtration chromatography and western blot showed combinations of rMeISA1 and rMeISA2 at ratios of 1:1 to 4:1. Pooled fractions with DBE activity were used for enzyme characterisation, which showed that the enzyme was specific for amylopectin, with optimum activity at 37 °C and pH 7.0. Enzyme activity was enhanced by Co 2+ , Mg 2+ and Ca 2+ , but was strongly inhibited by Cu 2+ . Debranched amylopectin products showed chain length distributions typical of plant DBE.

Association of SNPs from IL1A, IL1B, and IL6 Genes with Human Cytomegalovirus Infection Among Pregnant Women.

PubMed

Wujcicka, Wioletta Izabela; Wilczyński, Jan Szczęsny; Nowakowska, Dorota Ewa

2017-05-01

The study was aimed to estimate the role and prevalence rates of genotypes, haplotypes, and alleles, located within the single-nucleotide polymorphisms (SNPs) of interleukin (IL) 1A, IL1B, and IL6 genes, in the occurrence and development of human cytomegalovirus (HCMV) infection among pregnant women. A research was conducted in 129 pregnant women, out of whom, 65 were HCMV infected and 64 were age-matched control uninfected individuals. HCMV DNA was quantitated for UL55 gene by the real-time Q PCR in the body fluids. The genotypic statuses within the SNPs were determined by nested PCR-RFLP assays and confirmed, by sequencing for randomly selected representative PCR products. A relationship between the genotypes and alleles, as well as haplotypes and multiple variants in the studied polymorphisms, and the occurrence of HCMV infection in pregnant women, was determined using a logistic regression model. TT genotype within IL1A polymorphism significantly decreased the risk of HCMV infection (OR 0.32, 95% CI 0.09-1.05; p ≤ 0.050). Considering IL6 SNP, the prevalence rate of GC genotype was significantly decreased among the HCMV infected, compared to the uninfected control individuals (OR 0.45, 95% CI 0.21-0.99; p ≤ 0.050). Moreover, CC homozygotic status in IL6 SNP, found in pregnant women, significantly decreased the risk of congenital infection with HCMV in their offsprings (OR 0.12; p ≤ 0.050). In multiple SNP analysis, TC haplotype within the IL1 polymorphisms significantly decreased the risk of the infection in pregnant women (OR 0.38 95% CI 0.15-0.96; p ≤ 0.050). In addition, TTG complex variants for all the studied polymorphisms and TG variants for IL1B and IL6 SNPs were significantly more prevalent among the infected offsprings with symptomatic congenital cytomegaly than among the asymptomatic cases (p ≤ 0.050). In conclusion, the analyzed IL1A -889 C>T, IL1B +3954 C>T, and IL6 -174 G>C polymorphisms may be associated with the occurrence and development of HCMV infection among studied patients.

Polymorphism of the insulin gene is associated with increased prostate cancer risk.

PubMed

Ho, G Y F; Melman, A; Liu, S-M; Li, M; Yu, H; Negassa, A; Burk, R D; Hsing, A W; Ghavamian, R; Chua, S C

2003-01-27

High insulin levels are linked with increased cancer risk, including prostate cancer. We examined the associations between prostate cancer with polymorphisms of the insulin gene (INS) and its neighbouring genes, tyrosine-hydroxylase and IGF-II (TH and IGF2). In this study, 126 case-control pairs matched on age, race, and countries of origin were genotyped for +1127 INS-PstI in INS, -4217 TH-PstI in TH, and +3580 IGF2-MspI in IGF2. The homozygous CC genotype of +1127 INS-PstI occurred in over 60% of the population. It was associated with an increased risk of prostate cancer in nondiabetic Blacks and Caucasians (OR=3.14, P=0.008). The CC genotype was also associated with a low Gleason score <7 (OR=2.60, P=0.022) and a late age of diagnosis (OR=2.10, P=0.046). Markers in the neighbouring genes of INS showed only null to modest associations with prostate cancer. The polymorphism of INS may play a role in the aetiology of prostate cancer. Given the high prevalence of the CC genotype and its association with late age of onset of low-grade tumours, this polymorphism may contribute to the unique characteristics of prostate cancer, namely a high prevalence of indolent cancers and the dramatic increase in incidence with age.

Arylamine N-acetyltransferase 2 gene polymorphism in an Algerian population.

PubMed

Chelouti, Hiba; Khelil, Malika

2017-09-01

The arylamine N-acetyltransferase 2 (NAT2) is a key enzyme in the biotransformation of xenobiotics. NAT2 gene polymorphisms have been associated with the risk of isoniazid hepatotoxicity and these polymorphisms change among different populations. The objective of this study is to investigate NAT2 polymorphisms in order to predict the prevalence of NAT2 phenotype in an Algerian population. Genotyping of NAT2 was done using a PCR-RFLP method. Haplotype was analysed using the software package PHASE, version 2.0. The major haplotypes were NAT2*5B (23.72%), NAT2*6 A (18.61%), NAT2*4 (14.60%) and NAT2*5 F (10%). The average of the expected slow acetylator phenotype was 53%. Our results suggest that the high frequency of slow acetylator phenotype requires investigation into its possible association with ATDH.

New aspects in pathogenesis of konzo: neural cell damage directly caused by linamarin contained in cassava (Manihot esculenta Crantz).

PubMed

Sreeja, V G; Nagahara, N; Li, Q; Minami, M

2003-08-01

Epidemic spastic paraparesis (konzo) found in tropical and subtropical countries is known to be caused by long-term intake of cassava (Manihot esculenta Crantz), which contains a cyanoglucoside linamarin (alpha-hydroxyisobutyronitrile-beta-d-glucopyranoside). It has been reported that linamarin is enzymatically converted to cyanide by bacteria in the intestine, and this is absorbed into the blood and then damages neural cells. However, unmetabolized linamarin was found in the urine after oral administration of cassava; thus, we hypothesized that konzo could be caused by direct toxicity of the unmetabolized linamarin that was transferred to the brain and could be transported into neural cells via a glucose transporter. In the present study it was confirmed that linamarin directly damaged neural culture pheochromocytoma cell (PC) 12 cells; 0.10 mm-linamarin caused cell death at 13.31 (SD 2.07) %, which was significantly different from that of control group (3.18 (SD 0.92) %, P=0.0004). Additional 10 microM-cytochalasin B, an inhibitor of a glucose transporter, prevented cell death: the percentage of dead cells significantly decreased to 6.06 (SD 1.98), P=0.0088). Furthermore, glucose also prevented cell death. These present results strongly suggest that linamarin competes with cytochalasin B and glucose for binding to a glucose transporter and enters into cells via glucose transporter.

Diallel analysis of provitamin A carotenoid and dry matter content in cassava (Manihot esculenta Crantz)

PubMed Central

Esuma, Williams; Kawuki, Robert S.; Herselman, Liezel; Labuschagne, Maryke Tine

2016-01-01

Global efforts are underway to biofortify cassava (Manihot esculenta Crantz) with provitamin A carotenoids to help combat dietary vitamin A deficiency afflicting the health of more than 500 million resource-poor people in Sub-Saharan Africa. To further the biofortification initiative in Uganda, a 6×6 diallel analysis was conducted to estimate combining ability of six provitamin A clones and gene actions controlling total carotenoid content (TCC), dry matter content (DMC) in cassava roots and other relevant traits. Fifteen F1 families generated from the diallel crosses were evaluated in two environments using a randomized complete block design. General combining ability (GCA) effects were significant for TCC and DMC, suggesting the relative importance of additive gene effects in controlling these traits in cassava. On the other hand, non-additive effects were predominant for root and shoot weight. MH02-073HS, with the highest level of TCC, was the best general combiner for TCC while NASE 3, a popular white-fleshed variety grown by farmers in Uganda, was the best general combiner for DMC. Such progenitors with superior GCA effects could form the genetic source for future programs targeting cassava breeding for TCC and DMC. A negative correlation was observed between TCC and DMC, which will require breeding strategies to combine both traits for increased adoption of provitamin A cassava varieties. PMID:27795688

Pollen flow in the wildservice tree, Sorbus torminalis (L.) Crantz. II. Pollen dispersal and heterogeneity in mating success inferred from parent-offspring analysis.

PubMed

Oddou-Muratorio, Sylvie; Klein, Etienne K; Austerlitz, Frédéric

2005-12-01

Knowing the extent of gene movements from parents to offspring is essential to understand the potential of a species to adapt rapidly to a changing environment, and to design appropriate conservation strategies. In this study, we develop a nonlinear statistical model to jointly estimate the pollen dispersal kernel and the heterogeneity in fecundity among phenotypically or environmentally defined groups of males. This model uses genotype data from a sample of fruiting plants, a sample of seeds harvested on each of these plants, and all males within a circumscribed area. We apply this model to a scattered, entomophilous woody species, Sorbus torminalis (L.) Crantz, within a natural population covering more than 470 ha. We estimate a high heterogeneity in male fecundity among ecological groups, both due to phenotype (size of the trees and flowering intensity) and landscape factors (stand density within the neighbourhood). We also show that fat-tailed kernels are the most appropriate to depict the important abilities of long-distance pollen dispersal for this species. Finally, our results reveal that the spatial position of a male with respect to females affects as much its mating success as ecological determinants of male fecundity. Our study thus stresses the interest to account for the dispersal kernel when estimating heterogeneity in male fecundity, and reciprocally.

Phytochemical Characterization of Veronica officinalis L., V. teucrium L. and V. orchidea Crantz from Romania and Their Antioxidant and Antimicrobial Properties

PubMed Central

Mocan, Andrei; Vodnar, Dan Cristian; Vlase, Laurian; Crișan, Ovidiu; Gheldiu, Ana-Maria; Crișan, Gianina

2015-01-01

Aerial parts of Veronica species are used in Romanian traditional medicine for the treatment of various conditions like kidney diseases, cough, and catarrh, and are known for their wound-healing properties. In the present study, the phenolic and sterolic content and the antioxidant and antimicrobial activities of three Veronica species (Plantaginaceae), V. officinalis L., V. teucrium L. and V. orchidea Crantz, were studied. The identification and quantification of several phenolic compounds and phytosterols were performed using LC/MS techniques and the main components were p-coumaric acid, ferulic acid, luteoline, hispidulin and β-sitosterol. More than that, hispidulin, eupatorin and eupatilin were detected for the first time in the Veronica genus. Nevertheless, representatives of the Veronica genus were never investigated in terms of their phytosterol content. The antioxidant potential investigated by Trolox equivelents antioxidant capacity (TEAC) and EPR spectroscopy revealed that V. officinalis and V. orchidea extracts presented similar antioxidant capacities, whilst the values registered for V. teucrium extract are lower. Regarding the antimicrobial activity of the investigated species, Staphylococcus aureus, Listeria monocytogenes and Listeria ivanovii were the most sensitive strains with MIC values between 3.9 and 15.62 mg/mL. The results obtained by this study may serve to promote better use of representatives from the genus Veronica as antioxidant and antimicrobial agents. PMID:26404257

Gene-Environment Interaction in Parkinson's Disease: Coffee, ADORA2A, and CYP1A2.

PubMed

Chuang, Yu-Hsuan; Lill, Christina M; Lee, Pei-Chen; Hansen, Johnni; Lassen, Christina F; Bertram, Lars; Greene, Naomi; Sinsheimer, Janet S; Ritz, Beate

2016-01-01

Drinking caffeinated coffee has been reported to provide protection against Parkinson's disease (PD). Caffeine is an adenosine A2A receptor (encoded by the gene ADORA2A) antagonist that increases dopaminergic neurotransmission and Cytochrome P450 1A2 (gene: CYP1A2) metabolizes caffeine; thus, gene polymorphisms in ADORA2A and CYP1A2 may influence the effect coffee consumption has on PD risk. In a population-based case-control study (PASIDA) in Denmark (1,556 PD patients and 1,606 birth year- and gender-matched controls), we assessed interactions between lifetime coffee consumption and 3 polymorphisms in ADORA2A and CYP1A2 for all subjects, and incident and prevalent PD cases separately using logistic regression models. We also conducted a meta-analysis combining our results with those from previous studies. We estimated statistically significant interactions for ADORA2A rs5760423 and heavy vs. light coffee consumption in incident (OR interaction = 0.66 [95% CI 0.46-0.94], p = 0.02) but not prevalent PD. We did not observe interactions for CYP1A2 rs762551 and rs2472304 in incident or prevalent PD. In meta-analyses, PD associations with daily coffee consumption were strongest among carriers of variant alleles in both ADORA2A and CYP1A2. We corroborated results from a previous report that described interactions between ADORA2A and CYP1A2 polymorphisms and coffee consumption. Our results also suggest that survivor bias may affect results of studies that enroll prevalent PD cases. © 2017 S. Karger AG, Basel.

[Homocysteinemia and its relationship with the methylentetrahydrofolate reductase polymorphism in various ethnic groups from western Venezuela].

PubMed

Vizcaíno, Gilberto; Diez-Ewald, María; Herrmann, Falko H; Schuster, Gudrun; Torres-Guerra, Enrique; Arteaga-Vizcaíno, Melvis

2005-12-01

The prevalence of hyperhomocysteinemia and C677T MTHFR polymorphism was studied in various ethnic groups from Western Venezuela (60 Wayuu Indians, 42 italian immigrants and 77 Venezuelan mestizos) in relation with the prevalence of hyperhomocysteinemia and the C677T MTHFR polymorphism. Homocysteinemia was determined by polarized fluorescence immunoassay in an IMX system, serum folate was measured by radioimmunoanalysis and the MTHFR genotype was determined by PCR and restriction analysis. Hyperhomocysteinemia was defined as a value over 2 SD above the mean value for normal MTHFR (CC677) in each group. The prevalence of MTHFR variants (C677T and 677TT) was elevated in all ethnic groups (78% among the wayuu, 76% among Italians and 63% among mestizos) with a significant association between the concentrations of homocysteine and the levels of serum folate among the wayuu (p < 0.0001) and the mestizos (p < 0.001) only. Hyperhomocysteinemia was associated with MTHFR variants in 23% of the wayuu (OR: 6.17, CI 95: 0.74-51.36), 9.5% of the Italians (OR: 0.93, CI 95: 0.085-10.10) and 20.7 of the Venezuelans mestizos (OR: 5.2, CI 95: 1.08-24.90, p > 0.03). There was no relationship between hyperhomocysteinemia and folate deficiency in any of the groups studied. In conclusion, despite a high prevalence of C677T MTHFR variants in these ethnic groups of western Venezuela, the lack of no evidence of hyperhomocysteinemia combined with folate deficiency may imply that the nutritional status of these groups plays an important role in the control of hyperhomocysteinemia as a risk factor for cardiovascular disease.

C677T polymorphism in the methylenetetrahydrofolate reductase gene is associated with primary closed angle glaucoma

PubMed Central

Michael, Shazia; Qamar, Raheel; Akhtar, Farah; Khan, Wajid Ali

2008-01-01

Purpose To determine whether or not there is an association of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with disease in cohorts of primary open-angle glaucoma (POAG) and primary closed-angle glaucoma (PCAG) from Pakistan. Methods This was a prospective study consisting of 150 patients (90 POAG and 60 PCAG) and 70 control subjects. Genomic DNA was extracted from leukocytes of the peripheral blood. MTHFR C677T polymorphism analysis was performed by the polymerase chain reaction-restriction fragment length polymorphism (RFLP) technique. Results The prevalence of the MTHFR C/T genotype was 22.2% in POAG, 13.3% in PACG, and 18.6% in controls whereas the MTHFR T/T genotype was present solely in the PACG group (6.9%). The difference regarding the T/T genotype between PACG and controls was statistically significant (p<0.01). Conclusions The MTHFR C677T polymorphism was found to be associated with PCAG but not POAG in patients of Pakistani origin. PMID:18385801

APOE, MTHFR, LDLR and ACE polymorphisms among Angami and Lotha Naga populations of Nagaland, India.

PubMed

Murry, Benrithung; Vakha, Neikethono; Achoubi, Nongthombam; Sachdeva, M P; Saraswathy, K N

2011-12-01

Several common polymorphisms in the ApoE, ACE, MTHFR and LDLR genes have been implicated in the pathogenesis of common complex diseases across world populations. This study investigates the prevalence of five known and clinically important common polymorphisms in Angami and Lotha Naga populations. A total of 112 unrelated healthy volunteers (52 Lotha Nagas and 60 Angami Nagas) participated in the study. All the five genes were found to be polymorphic in the studied populations. The Lotha Nagas displayed higher mutant allele frequencies than the Angami Nagas except for the T allele frequency of the AvaII polymorphism of the LDLR gene, though chi square did not reveal any significant population differences by genotypes. In view of the relatively high mutant allele frequencies in both the populations, they are likely to be at a high risk of developing various complex diseases as they shift from an active and rigorous lifestyle to a more sedentary one.

Clinical response to chemotherapy in locally advanced breast cancer was not associated with several polymorphisms in detoxification enzymes and DNA repair genes.

PubMed

Saadat, Mostafa; Khalili, Maryam; Nasiri, Meysam; Rajaei, Mehrdad; Omidvari, Shahpour; Saadat, Iraj

2012-03-02

The main aim of the present study was to investigate the association between several genetic polymorphisms (in glutathione S-transferase members and DNA repair genes) and clinical response to chemotherapy in locally advanced breast cancer. A sequential series of 101 patients were prospectively included in this study. Clinical assessment of treatment was accomplished by comparing initial tumor size with preoperative tumor size using revised RECIST guideline (version 1.1). Clinical response was regarded as a response or no response. There was no difference between non-responders and responders for the prevalence of genotypes of the study polymorphisms. Copyright © 2012 Elsevier Inc. All rights reserved.

[Alzheimer's disease and methylenetetrahydrofolate reductase gene polymorphisms: a potential nutrigenomic approach for Mexico].

PubMed

Castillo-Quan, Jorge I; Pérez-Osorio, Julia M

2009-01-01

The establishment of medical genomics in Mexico offers the possibility to study in a more comprehensive manner the etiological factors of different diseases, providing a global view of the interaction between the genome and the environment. Nutrition is recognized as a significant determinant in several diseases, yet its interaction with polymorphisms, and in general with the genome, has not been properly addressed Mexico has a high prevalence of polymorphisms of the methylenetetrahydrofolate reductase gene, and in both clinical and basic studies this has been associated with an increased susceptibility of developing Alzheimer's disease. We propose a potential nutrigenomic approach for the study of Alzheimer disease in Mexico.

Association of single nucleotide polymorphisms in the gene encoding GLUT1 and diabetic nephropathy in Brazilian patients with type 1 diabetes mellitus.

PubMed

Marques, T; Patente, T A; Monteiro, M B; Cavaleiro, A M; Queiroz, M S; Nery, M; de Azevedo, M J; Canani, L H; Parisi, M C; Moura-Neto, A; Passarelli, M; Giannella-Neto, D; Machado, U F; Corrêa-Giannella, M L

2015-04-15

Mesangial cells subject to high extracellular glucose concentrations, as occur in hyperglycaemic states, are unable to down regulate glucose influx, resulting in intracellular activation of deleterious biochemical pathways. A high expression of GLUT1 participates in the development of diabetic glomerulopathy. Variants in the gene encoding GLUT1 (SLC2A1) have been associated to this diabetic complication. The aim of this study was to test whether polymorphisms in SLC2A1 confer susceptibility to diabetic nephropathy (DN) in Brazilian type 1 diabetes patients. Four polymorphisms (rs3820589, rs1385129, rs841847 and rs841848) were genotyped in a Brazilian cohort comprised of 452 patients. A prospective analysis was performed in 155 patients. Mean duration of follow-up was 5.6 ± 2.4 years and the incidence of renal events was 18.0%. The rs3820589 presented an inverse association with the prevalence of incipient DN (OR: 0.36, 95% CI: 0.16 - 0.80, p=0.01) and with progression to renal events (HR: 0.20; 95% CI: 0.03 - 0.70; p=0.009). AGGT and AGAC haplotypes were associated with the prevalence of incipient DN and the AGAC haplotype was also associated with the prevalence of established/advanced DN. In conclusion, rs3820589 in the SLC2A1 gene modulates the risk to DN in Brazilian patients with inadequate type 1 diabetes control. Copyright © 2015 Elsevier B.V. All rights reserved.

Polymorphism of the Transcription Factor 7-Like 2 Gene (TCF7L2) Interacts with Obesity on Type-2 Diabetes in the PREDIMED Study Emphasizing the Heterogeneity of Genetic Variants in Type-2 Diabetes Risk Prediction: Time for Obesity-Specific Genetic Risk Scores.

PubMed

Corella, Dolores; Coltell, Oscar; Sorlí, Jose V; Estruch, Ramón; Quiles, Laura; Martínez-González, Miguel Ángel; Salas-Salvadó, Jordi; Castañer, Olga; Arós, Fernando; Ortega-Calvo, Manuel; Serra-Majem, Lluís; Gómez-Gracia, Enrique; Portolés, Olga; Fiol, Miquel; Díez Espino, Javier; Basora, Josep; Fitó, Montserrat; Ros, Emilio; Ordovás, José M

2016-12-06

Nutrigenetic studies analyzing gene-diet interactions of the TCF7L2-rs7903146 C > T polymorphism on type-2 diabetes (T2D) have shown controversial results. A reason contributing to this may be the additional modulation by obesity. Moreover, TCF7L2-rs7903146 is one of the most influential variants in T2D-genetic risk scores (GRS). Therefore, to increase the predictive value (PV) of GRS it is necessary to first see whether the included polymorphisms have heterogeneous effects. We comprehensively investigated gene-obesity interactions between the TCF7L2-rs7903146 C > T polymorphism on T2D (prevalence and incidence) and analyzed other T2D-polymorphisms in a sub-sample. We studied 7018 PREDIMED participants at baseline and longitudinally (8.7 years maximum follow-up). Obesity significantly interacted with the TCF7L2-rs7903146 on T2D prevalence, associations being greater in non-obese subjects. Accordingly, we prospectively observed in non-T2D subjects ( n = 3607) that its association with T2D incidence was stronger in non-obese (HR: 1.81; 95% CI: 1.13-2.92, p = 0.013 for TT versus CC) than in obese subjects (HR: 1.01; 95% CI: 0.61-1.66; p = 0.979; p -interaction = 0.048). Accordingly, TCF7L2-PV was higher in non-obese subjects. Additionally, we created obesity-specific GRS with ten T2D-polymorphisms and demonstrated for the first time their higher strata-specific PV. In conclusion, we provide strong evidence supporting the need for considering obesity when analyzing the TCF7L2 effects and propose the use of obesity-specific GRS for T2D.

Prevalence of K13-propeller gene polymorphisms among Plasmodium falciparum parasites isolated from adult symptomatic patients in northern Uganda.

PubMed

Ocan, Moses; Bwanga, Freddie; Okeng, Alfred; Katabazi, Fred; Kigozi, Edgar; Kyobe, Samuel; Ogwal-Okeng, Jasper; Obua, Celestino

2016-08-19

In the absence of an effective vaccine, malaria treatment and eradication is still a challenge in most endemic areas globally. This is especially the case with the current reported emergence of resistance to artemisinin agents in Southeast Asia. This study therefore explored the prevalence of K13-propeller gene polymorphisms among Plasmodium falciparum parasites in northern Uganda. Adult patients (≥18 years) presenting to out-patients department of Lira and Gulu regional referral hospitals in northern Uganda were randomly recruited. Laboratory investigation for presence of plasmodium infection among patients was done using Plasmodium falciparum exclusive rapid diagnostic test, histidine rich protein-2 (HRP2) (Pf). Finger prick capillary blood from patients with a positive malaria test was spotted on a filter paper Whatman no. 903. The parasite DNA was extracted using chelex resin method and sequenced for mutations in K13-propeller gene using Sanger sequencing. PCR DNA sequence products were analyzed using in DNAsp 5.10.01software, data was further processed in Excel spreadsheet 2007. A total of 60 parasite DNA samples were sequenced. Polymorphisms in the K13-propeller gene were detected in four (4) of the 60 parasite DNA samples sequenced. A non-synonymous polymorphism at codon 533 previously detected in Cambodia was found in the parasite DNA samples analyzed. Polymorphisms at codon 522 (non-synonymous) and codon 509 (synonymous) were also found in the samples analyzed. The study found evidence of positive selection in the Plasmodium falciparum population in northern Uganda (Tajima's D = -1.83205; Fu and Li's D = -1.82458). Polymorphism in the K13-propeller gene previously reported in Cambodia has been found in the Ugandan Plasmodium falciparum parasites. There is need for continuous surveillance for artemisinin resistance gene markers in the country.

Frequencies of CYP2C9 polymorphisms in North Indian population and their association with drug levels in children on phenytoin monotherapy.

PubMed

Chaudhary, Nagendra; Kabra, Madhulika; Gulati, Sheffali; Gupta, Yogendra Kumar; Pandey, Ravindra Mohan; Bhatia, Bal Dev

2016-05-14

Phenytoin, mainly metabolized by cytochrome P450 enzyme system, has a narrow therapeutic index and may have adverse effects due to inter-individual variation in the dose requirement and genetic polymorphisms. This cross-sectional study was done to study the prevalence of cytochrome P450 CYP2C9 polymorphisms in Indian epileptic children and to see the effect of polymorphisms on serum levels in epileptic children on phenytoin monotherapy. We studied 89 epileptic children of North Indian population, randomly selected, to see the genotypic and allelic frequency of CYP2C9 and its association with drug levels on phenytoin monotherapy. Analysis was done using STATA 9 Software. The results were analyzed as prevalence at 95 % C.I. (Confidence Interval). The difference in mean phenytoin serum levels between wild and mutant alleles was tested using Student`s T test for independent samples. P value less than 0.05 was considered statistically significant. CYP2C9*1, *2 & *3 allelic frequencies were 85.4, 4.5 and 10.1 % respectively. CYP2C9*3 allelic group showed significantly higher serum phenytoin levels compared to the wild variants (P = 0.009). There was no statistically significant difference in the dose received (P = 0.12) and side effects of CYP2C9*2 and CYP2C9*3 genotypes (P = 0.442 and 0.597 respectively) when compared with wild variant. CYP2C9*3 is more common than *2 in the present study. All the polymorphisms demonstrated in our study were heterozygous with no homozygosity. Serum phenytoin levels are higher in polymorphic groups (*3) which suggest their poor metabolizing nature. Genotyping may help to avoid toxicity and concentration-dependent adverse effects.

Aspirin resistance in cerebrovascular disease and the role of glycoprotein IIIa polymorphism in Turkish stroke patients.

PubMed

Derle, Eda; Öcal, Ruhsen; Kibaroğlu, Seda; Çelikkol, Ceyda; Bayraktar, Nilüfer; Verdi, Hasibe; Ataç, Belgin F; Can, Ufuk

2016-03-01

Aspirin resistance occurs in 5-45% of high-risk patients, with various mechanisms proposed for its development. This study aimed to determine the relationships among aspirin resistance, aspirin dosage, type of aspirin and glycoprotein IIIa P1A1/A2 polymorphism in patients with vascular risk factors. Two hundred and eight (75 symptomatic, 133 asymptomatic) patients with vascular risk factors who were using aspirin for primary or secondary prevention were prospectively included. The symptomatic group was further classified into two groups according to aspirin use at the time of stroke. Aspirin resistance was measured by the PFA-100 system (collagen/epinephrine cartridge) and glycoprotein IIIa P1A1/A2 polymorphism was determined by PCR. The overall prevalence of aspirin resistance was 32.2%. The mean age of patients with aspirin resistance was significantly higher than that in those who did not have resistance (P = 0.009). The prevalence of aspirin resistance was similar for the symptomatic and asymptomatic under aspirin therapy groups. The resistance rate was found to be highest with 100 mg enteric-coated preparation use (39.3%). Increasing the aspirin dosage and/or shifting to uncoated preparations caused a change in aspirin sensitivity of 36-60%. Repeated measurements showed development of aspirin resistance in 14% of patients who were sensitive to aspirin in previous measurements. Glycoprotein IIIaP1A1/A2 polymorphism, aspirin resistance and development of atherothrombotic stroke were not significantly related. The effect of aspirin can change by time, dosage and type of preparation used. There are no relationships among glycoprotein IIIa P1A1/A2 polymorphism, aspirin resistance and development of atherothrombotic stroke.

Human immunodeficiency virus type 1 seroprevalence and antiretroviral drug resistance-associated mutations in miners in Gabon, central Africa.

PubMed

Caron, Mélanie; Makuwa, Maria; Souquière, Sandrine; Descamps, Diane; Brun-Vézinet, Françoise; Kazanji, Mirdad

2008-09-01

Miners in sub-Saharan African are known to have an extremely high prevalence of HIV-1 infection. We therefore evaluated the prevalence of HIV-1 infection among manganese miners in Gabon, central Africa and examined the diversity of HIV-1 strains by characterizing the polymorphism of the pol gene in order to observe drug resistance-associated mutations. In 857 samples tested, the HIV-1 prevalence was 2.9%. By pol sequence analysis, we showed that all the HIV-1 strains belonged to group M, with a majority of CRF02_AG (57%) followed by subtype A (9%) and CRF01_AE or subtype B (4%). The remaining HIV-1 strains demonstrated discordant genomic results and exhibited a mosaic pol genome (30%). Most of the mutations detected in pol coding regions corresponded to the subtype polymorphism, with no specific antiretroviral drug resistance. To avoid the rapid emergence of resistant viruses in this part of central Africa, continuous surveillance of the circulation of drug-resistant viruses must be maintained to guide treatment strategies.

Association of polymorphisms in microRNA machinery genes (DROSHA, DICER1, RAN, and XPO5) with risk of idiopathic primary ovarian insufficiency in Korean women.

PubMed

Rah, HyungChul; Jeon, Young Joo; Lee, Bo Eun; Kim, Jung O; Shim, Sung Han; Lee, Woo Sik; Choi, Dong Hee; Kim, Ji Hyang; Kim, Nam Keun

2013-10-01

The aim of our study was to investigate whether polymorphisms in microRNA machinery genes are associated with the risk of primary ovarian insufficiency (POI). We genotyped 136 POI patients and 236 controls among Korean women for nine single nucleotide polymorphisms (SNPs; DROSHA rs6877842 and rs10719; DICER1 rs13078 and rs3742330; RAN rs14035; and XPO5 rs34324334, rs2257082, rs11544382, and rs11077) by polymerase chain reaction-restriction fragment length polymorphism analysis. Differences in genotype frequencies between patients and controls were compared, and odds ratios (ORs) and 95% CIs were determined as measures of the strength of the association between genotype and POI. Of the nine SNPs, XPO5 rs34324334 and rs11544382 were monomorphic and were not analyzed further. The XPO5 rs2257082 CT and CT + TT variant genotypes were more frequent in patients (OR, 2.097; 95% CI, 1.207-3.645) than in controls (OR, 2.030; 95% CI, 1.196-3.445). The combined frequencies of XPO5 rs2257082 CT + TT and rs11077 AC + CC genotypes were higher in patients than in controls (OR, 2.526; 95% CI, 1.088-5.865). An association of POI risk with other polymorphisms was not found. A haplotype-based analysis of seven polymorphisms of the microRNA machinery genes for gene-gene interactions suggests that ***ACTA, ***GCCA, ***G*C*, *T*ATTA, and ***ACT* haplotypes (asterisk indicates SNP locus not included; DROSHA rs6877842 and rs10719, DICER1 rs13078 and rs3742330, RAN rs14035, and XPO5 rs2257082 and rs11077 polymorphisms) are associated with higher POI prevalence, and that ***GCTA, ***ACCA, *C*ATTA, and *C*ATT* haplotypes are associated with lower POI prevalence. Our data demonstrate that the XPO5 rs2257082 T variant allele occurs more frequently in POI patients than in controls, suggesting that this allele may be associated with increased POI risk.

Apolipoprotein E gene polymorphism and gender.

PubMed

Kolovou, Genovefa; Damaskos, Dimitris; Anagnostopoulou, Katherine; Cokkinos, Dennis V

2009-01-01

Many studies have shown that the prevalence and onset of coronary heart disease (CHD) is sex-dependent. CHD prevalence is lower in women than in men at all ages. Furthermore, women's age of CHD onset seems to be 10 yr later. This is widely attributed to the fact that men have less favorable CHD risk factors (eg, plasma lipid profile) compared to women. Mean levels of protective high density lipoprotein cholesterol are lower, while triglyceride levels are higher in men than in women. It is possible that many of the genes involved in lipid metabolism, such as Apolipoprotein (Apo) E, as well as their polymorphisms, may be expressed in a sexually dimorphic manner. The human Apo E gene is polymorphic, encoding one of 3 common epsilon (epsilon) alleles (epsilon 2, epsilon 3, epsilon 4), with the epsilon 3 allele occurring most frequently (78%) in the Caucasian population. Association studies have shown a protective effect on CHD in epsilon 2 carriers and a harmful effect in epsilon 4 carriers. However, there are conflicting results regarding such allelic effects in respect to gender. This review is focused on the gender-related influence of Apo E polymorphism in respect to plasma lipid levels and the risk of CHD. Additionally, an effort is made to determine if this relation exists and if it can be satisfactorily explained. The studies cited here demonstrate a complex, multifactorial association between these factors, in need of further corroboration in greater population samples.

K13-propeller polymorphisms in Plasmodium falciparum parasites from sub-Saharan Africa.

PubMed

Kamau, Edwin; Campino, Susana; Amenga-Etego, Lucas; Drury, Eleanor; Ishengoma, Deus; Johnson, Kimberly; Mumba, Dieudonne; Kekre, Mihir; Yavo, William; Mead, Daniel; Bouyou-Akotet, Marielle; Apinjoh, Tobias; Golassa, Lemu; Randrianarivelojosia, Milijaona; Andagalu, Ben; Maiga-Ascofare, Oumou; Amambua-Ngwa, Alfred; Tindana, Paulina; Ghansah, Anita; MacInnis, Bronwyn; Kwiatkowski, Dominic; Djimde, Abdoulaye A

2015-04-15

Mutations in the Plasmodium falciparum K13-propeller domain have recently been shown to be important determinants of artemisinin resistance in Southeast Asia. This study investigated the prevalence of K13-propeller polymorphisms across sub-Saharan Africa. A total of 1212 P. falciparum samples collected from 12 countries were sequenced. None of the K13-propeller mutations previously reported in Southeast Asia were found, but 22 unique mutations were detected, of which 7 were nonsynonymous. Allele frequencies ranged between 1% and 3%. Three mutations were observed in >1 country, and the A578S was present in parasites from 5 countries. This study provides the baseline prevalence of K13-propeller mutations in sub-Saharan Africa. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

CRISPR Typing and Subtyping for Improved Laboratory Surveillance of Salmonella Infections

PubMed Central

Fabre, Laëtitia; Zhang, Jian; Guigon, Ghislaine; Le Hello, Simon; Guibert, Véronique; Accou-Demartin, Marie; de Romans, Saïana; Lim, Catherine; Roux, Chrystelle; Passet, Virginie; Diancourt, Laure; Guibourdenche, Martine; Issenhuth-Jeanjean, Sylvie; Achtman, Mark; Brisse, Sylvain; Sola, Christophe; Weill, François-Xavier

2012-01-01

Laboratory surveillance systems for salmonellosis should ideally be based on the rapid serotyping and subtyping of isolates. However, current typing methods are limited in both speed and precision. Using 783 strains and isolates belonging to 130 serotypes, we show here that a new family of DNA repeats named CRISPR (clustered regularly interspaced short palindromic repeats) is highly polymorphic in Salmonella. We found that CRISPR polymorphism was strongly correlated with both serotype and multilocus sequence type. Furthermore, spacer microevolution discriminated between subtypes within prevalent serotypes, making it possible to carry out typing and subtyping in a single step. We developed a high-throughput subtyping assay for the most prevalent serotype, Typhimurium. An open web-accessible database was set up, providing a serotype/spacer dictionary and an international tool for strain tracking based on this innovative, powerful typing and subtyping tool. PMID:22623967

Single nucleotide polymorphisms related to cystic fibrosis in chronic rhinositus-a pilot study.

PubMed

Hull, Benjamin P; Jiramongkolchai, Pawina; Turner, Justin H; Olson, Lana; Chandra, Rakesh K

2017-05-01

The clinical association between cystic fibrosis (CF) and chronic rhinosinusitis (CRS) is well known. Studies have identified several non-CF transmembrane conductance regulator single nucleotide polymorphisms (SNPs) associated with disease severity in CF patients. We hypothesized that prevalence of these SNPs would be different between CRS patients and age/gender-matched non-CRS controls. This is a targeted SNP study of 1231 CRS patients identified through a large university hospital database who were compared with 8796 age- and gender-matched controls without a history of rhinitis, sinusitis, allergies, or asthma. Prevalence of 5 relevant SNPs was compared between groups, with p < 0.05 considered significant. Stratification by race and gender was performed among groups when statistically appropriate. CRS patients exhibited a statistically significant (p = 0.036) lower prevalence of rs12883884 (associated with an ion transporter) compared with controls. This association was lost when patients were stratified by race. CRS patients manifested a greater prevalence of rs1403543 (chromosome 23) in both Caucasian and African American subgroups (p = 0.036 and p = 0.026, respectively). Statistical significance disappeared among Caucasians when stratified by gender, but persisted among African American women (p = 0.047). rs12188164 and rs12793173 were both more prevalent in African Americans with CRS than controls (p = 0.042 and p = 0.020, respectively). A trend was also observed for decreased prevalence of rs12883884 in CRS patients compared with controls in the African American subgroup (p = 0.086). The identified SNPs were differentially prevalent in CRS compared with control groups, with some variability as a function of race and gender. Further research is required to confirm these findings and elucidate clinical significance. © 2017 ARS-AAOA, LLC.

High-resolution identification and abundance profiling of cassava (Manihot esculenta Crantz) microRNAs.

PubMed

Khatabi, Behnam; Arikit, Siwaret; Xia, Rui; Winter, Stephan; Oumar, Doungous; Mongomake, Kone; Meyers, Blake C; Fondong, Vincent N

2016-01-28

Small RNAs (sRNAs) are endogenous sRNAs that play regulatory roles in plant growth, development, and biotic and abiotic stress responses. In plants, one subset of sRNAs, microRNAs (miRNAs) exhibit tissue-differential expression and regulate gene expression mainly through direct cleavage of mRNA or indirectly via production of secondary phased siRNAs (phasiRNAs) that silence cognate target transcripts in trans. Here, we have identified cassava (Manihot esculenta Crantz) miRNAs using high resolution sequencing of sRNA libraries from leaf, stem, callus, male and female flower tissues. To analyze the data, we built a cassava genome database and, via sequence analysis and secondary structure prediction, 38 miRNAs not previously reported in cassava were identified. These new cassava miRNAs included two miRNAs not previously been reported in any plant species. The miRNAs exhibited tissue-differential accumulation as confirmed by quantitative RT-PCR and Northern blot analysis, largely reflecting levels observed in sequencing data. Some of the miRNAs identified were predicted to trigger production of secondary phased siRNAs (phasiRNAs) from 80 PHAS loci. Cassava is a woody perennial shrub, grown principally for its starch-rich storage roots, which are rich in calories. In this study, new miRNAs were identified and their expression was validated using qRT-PCR of RNA from five different tissues. The data obtained expand the list of annotated miRNAs and provide additional new resources for cassava improvement research.

Antibodies against oxidized LDL and apolipoprotein E polymorphism in demented patients.

PubMed

Bednarska-Makaruk, Małgorzata; Rodo, Maria; Graban, Ałła; Lojkowska, Wanda; Bochyńska, Anna; Ryglewicz, Danuta; Wehr, Hanna

2009-08-15

In serum of 114 patients with dementia and of 102 controls the level of IG class immunoglobulins directed against oxidized LDL and lipids were determined. In isolated DNA apolipoprotein E gene (APOE) polymorphism was identified. In some individuals very high levels of the antibodies were observed. exceeding the 90 percentile in the investigated group. The prevalence of very high anti-ox LDL antibodies level was significantly more frequent in the carriers of epsilon2 allele and less frequent in the carriers of epsilon4 allele.

Genetic polymorphisms and their association with the prevalence and severity of chronic postsurgical pain: a systematic review.

PubMed

Hoofwijk, D M N; van Reij, R R I; Rutten, B P; Kenis, G; Buhre, W F; Joosten, E A

2016-12-01

Although several patient characteristic, clinical, and psychological risk factors for chronic postsurgical pain (CPSP) have been identified, genetic variants including single nucleotide polymorphisms have also become of interest as potential risk factors for the development of CPSP. The aim of this review is to summarize the current evidence on genetic polymorphisms associated with the prevalence and severity of CPSP in adult patients. A systematic review of the literature was performed, and additional literature was obtained by reference tracking. The primary outcome was CPSP, defined as pain at least 2 months after the surgery. Studies performed exclusively in animals were excluded. Out of the 1001 identified studies, 14 studies were selected for inclusion. These studies described 5269 participants in 17 cohorts. A meta-analysis was not possible because of heterogeneity of data and data analysis. Associations with the prevalence or severity of CPSP were reported for genetic variants in the COMT gene, OPRM1, potassium channel genes, GCH1, CACNG, CHRNA6, P2X7R, cytokine-associated genes, human leucocyte antigens, DRD2, and ATXN1 CONCLUSIONS: Research on the topic of genetic variants associated with CPSP is still in its initial phase. Hypothesis-free, genome-wide association studies on large cohorts are needed in this field. In addition, future studies may also integrate genetic risk factors and patient characteristic, clinical, and psychological predictors for CPSP. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effect of the 5-HTTLPR polymorphism on affective temperament, depression and body mass index in obesity.

PubMed

Borkowska, A; Bieliński, M; Szczęsny, W; Szwed, K; Tomaszewska, M; Kałwa, A; Lesiewska, N; Junik, R; Gołębiewski, M; Sikora, M; Tretyn, A; Akiskal, K; Akiskal, H

2015-09-15

Many studies show high prevalence of affective disorders in obese patients. Affective temperament is a subclinical manifestation of such conditions. The 5-HTT gene encoding the serotonin transporter may be involved in both mood and eating dysregulation. The aim of this study was to investigate the influence of a polymorphism in the 5-HTT gene on affective temperament types, depressive symptoms and Body Mass Index (BMI) in obese patients. This study involved 390 patients (237 females, and 153 males) with obesity. The TEMPS-A questionnaire, Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS) were used to evaluate affective temperaments and prevalence of depression. DNA was obtained for serotonin transporter gene-linked polymorphism (5-HTTLPR) genotyping. In obese patients S/S genotype was associated with depressive and L/L with cyclothymic temperament. Subjects with L/L genotype presented significantly higher BMI and greater intensity of depressive symptoms in BDI and HDRS. Females scored higher in anxious and depressive, while males in hyperthymic, cyclothymic and irritable temperaments. Females scored higher in BDI (subjective depression) while males in HDRS (objective depression). TEMPS-A, BDI and HDRS are frequently used in studies on affective disorders. However, these methods do not examine all dimensions of mood and personality. In obese patients S allele of 5-HTTLPR was associated with development of depressive temperament while L allele corresponded with greater obesity and prevalence of depression. Different mechanisms may be involved in manifestation of depression in males and females with obesity. Copyright © 2015 Elsevier B.V. All rights reserved.

AFLP-based transcript profiling for cassava genome-wide expression analysis in the onset of storage root formation.

PubMed

Sojikul, Punchapat; Kongsawadworakul, Panida; Viboonjun, Unchera; Thaiprasit, Jittrawan; Intawong, Burapat; Narangajavana, Jarunya; Svasti, Mom Rajawong Jisnuson

2010-10-01

Cassava (Manihot esculenta Crantz) is a root crop that accumulates large quantities of starch, and it is an important source of carbohydrate. Study on gene expressions during storage root development provides important information on storage root formation and starch accumulation as well as unlock new traits for improving of starch yield. cDNA-Amplified Fragment Length Polymorphism (AFLP) was used to compare gene expression profiles in fibrous and storage roots of cassava cultivar Kasetsart 50. Total of 155 differentially expressed transcript-derived fragments with undetectable or low expression in leaves were characterized and classified into 11 groups regarding to their functions. The four major groups were no similarity (20%), hypothetical or unknown proteins (17%), cellular metabolism and biosynthesis (17%) and cellular communication and signaling (14%). Interestingly, sulfite reductase (MeKD82), calcium-dependent protein kinase (CDPK) (MeKD83), ent-kaurene synthase (KS) (MeKD106) and hexose transporter (HT) (MeKD154) showed root-specific expression patterns. This finding is consistent with previously reported genes involved in the initiation of potato tuber. Semi-quantitative reverse transcription polymerase chain reaction of early-developed root samples confirmed that those four genes exhibited significant expression with similar pattern in the storage root initiation and early developmental stages. We proposed that KS and HT may involve in transient induction of CDPK expression, which may play an important role in the signaling pathway of storage root initiation. Sulfite reductase, on the other hand, may involve in storage root development by facilitating sulfur-containing protein biosynthesis or detoxifying the cyanogenic glucoside content through aspartate biosynthesis. Copyright © Physiologia Plantarum 2010.

Regional Heritability Mapping Provides Insights into Dry Matter Content in African White and Yellow Cassava Populations.

PubMed

Okeke, Uche Godfrey; Akdemir, Deniz; Rabbi, Ismail; Kulakow, Peter; Jannink, Jean-Luc

2018-03-01

The HarvestPlus program for cassava ( Crantz) fortifies cassava with β-carotene by breeding for carotene-rich tubers (yellow cassava). However, a negative correlation between yellowness and dry matter (DM) content has been identified. We investigated the genetic control of DM in white and yellow cassava. We used regional heritability mapping (RHM) to associate DM with genomic segments in both subpopulations. Significant segments were subjected to candidate gene analysis and candidates were validated with prediction accuracies. The RHM procedure was validated via a simulation approach and revealed significant hits for white cassava on chromosomes 1, 4, 5, 10, 17, and 18, whereas hits for the yellow were on chromosome 1. Candidate gene analysis revealed genes in the carbohydrate biosynthesis pathway including plant serine-threonine protein kinases (SnRKs), UDP (uridine diphosphate)-glycosyltransferases, UDP-sugar transporters, invertases, pectinases, and regulons. Validation using 1252 unique identifiers from the SnRK gene family genome-wide recovered 50% of the predictive accuracy of whole-genome single nucleotide polymorphisms for DM, whereas validation using 53 likely genes (extracted from the literature) from significant segments recovered 32%. Genes including an acid invertase, a neutral or alkaline invertase, and a glucose-6-phosphate isomerase were validated on the basis of an a priori list for the cassava starch pathway, and also a fructose-biphosphate aldolase from the Calvin cycle pathway. The power of the RHM procedure was estimated as 47% when the causal quantitative trait loci generated 10% of the phenotypic variance (sample size = 451). Cassava DM genetics are complex and RHM may be useful for complex traits. Copyright © 2018 Crop Science Society of America.

Polymorphisms in candidate genes for type 2 diabetes mellitus in a Mexican population with metabolic syndrome findings.

PubMed

Sánchez-Corona, J; Flores-Martínez, S E; Machorro-Lazo, M V; Galaviz-Hernández, C; Morán-Moguel, M C; Perea, F J; Mújica-López, K I; Vargas-Ancona, L; Laviada-Molina, H A; Fernández, V; Pardío, J; Arroyo, P; Barrera, H; Hanson, R L

2004-01-01

The metabolic or insulin resistance syndrome, characterized by hypertension, dyslipidemia, glucose intolerance and hyperinsulinemia, may have genetic determinants. The insulin gene (INS), insulin receptor gene (INSR) and insulin receptor substrate 1 gene (IRS1) have been proposed as candidate genes. We examined eight polymorphisms in these genes in 163 individuals from Yucatan, Mexico; this population has a high prevalence of obesity, type 2 diabetes mellitus and dyslipidemia. Subjects were evaluated for body mass index (BMI) and blood pressure. Blood samples were collected to determine glucose, insulin, triglycerides and cholesterol levels, as well as for DNA isolation. Restriction fragment length polymorphisms in INS, INSR and IRS1 were identified by polymerase chain reaction and digestion with selected restriction enzymes. Among the eight polymorphisms analyzed, the PstI polymorphism in INS was significantly associated with hypertriglyceridemia and with the presence of at least one abnormality related to the metabolic syndrome (P=0.007 and 0.004, respectively). The MaeIII polymorphism in INS was associated with fasting hyperinsulinemia (P=0.045). In multilocus analyses including both INS polymorphisms, significant associations were seen with hypertriglyceridemia (P=0.006), hypercholesterolemia (P=0.031) and with presence of at least one metabolic abnormality (P=0.009). None of the polymorphisms in INSR or IRS1 was associated with any of these traits. These findings suggest that the insulin gene may be an important determinant of metabolic syndrome, and particularly of dyslipidemia, in this population.

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

9β Polymorphism of the Glucocorticoid Receptor Gene Appears to Have Limited Impact in Patients with Addison’s Disease

PubMed Central

Ross, Ian Louis; Dandara, Collet; Swart, Marelize; Lacerda, Miguel; Schatz, Desmond; Blom, Dirk Jacobus

2014-01-01

Background Addison’s disease (AD) has been associated with an increased risk of cardiovascular disease. Glucocorticoid receptor polymorphisms that alter glucocorticoid sensitivity may influence metabolic and cardiovascular risk factors in patients with AD. The 9β polymorphism of the glucocorticoid receptor gene is associated with relative glucocorticoid resistance and has been reported to increase the risk of myocardial infarction in the elderly. We explored the impact of this polymorphism in patients with AD. Materials and Methods 147 patients with AD and 147 age, gender and ethnicity matched healthy controls were recruited. Blood was taken in a non-fasted state for plasma lipid determination, measurement of cardiovascular risk factors and DNA extraction. Results Genotype data for the 9β polymorphism was available for 139 patients and 146 controls. AD patients had a more atherogenic lipid profile characterized by an increase in the prevalence of small dense LDL (p = 0.003), increased triglycerides (p = 0.002), reduced HDLC (p<0.001) an elevated highly sensitive C-reactive protein (p = 0.01), compared with controls. The 9β polymorphism (at least one G allele) was found in 28% of patients and controls respectively. After adjusting for age, gender, ethnicity, BMI and hydrocortisone dose per metre square of body surface area in patients, there were no significant metabolic associations with this polymorphism and hydrocortisone doses were not higher in patients with the polymorphism. Conclusions This study did not identify any associations between the 9β polymorphism and cardiovascular risk factors or hydrocortisone dose and determination of this polymorphism is therefore unlikely to be of clinical benefit in the management of patients with AD. PMID:24466047

9β Polymorphism of the glucocorticoid receptor gene appears to have limited impact in patients with Addison's disease.

PubMed

Ross, Ian Louis; Dandara, Collet; Swart, Marelize; Lacerda, Miguel; Schatz, Desmond; Blom, Dirk Jacobus

2014-01-01

Addison's disease (AD) has been associated with an increased risk of cardiovascular disease. Glucocorticoid receptor polymorphisms that alter glucocorticoid sensitivity may influence metabolic and cardiovascular risk factors in patients with AD. The 9β polymorphism of the glucocorticoid receptor gene is associated with relative glucocorticoid resistance and has been reported to increase the risk of myocardial infarction in the elderly. We explored the impact of this polymorphism in patients with AD. 147 patients with AD and 147 age, gender and ethnicity matched healthy controls were recruited. Blood was taken in a non-fasted state for plasma lipid determination, measurement of cardiovascular risk factors and DNA extraction. Genotype data for the 9β polymorphism was available for 139 patients and 146 controls. AD patients had a more atherogenic lipid profile characterized by an increase in the prevalence of small dense LDL (p = 0.003), increased triglycerides (p = 0.002), reduced HDLC (p<0.001) an elevated highly sensitive C-reactive protein (p = 0.01), compared with controls. The 9β polymorphism (at least one G allele) was found in 28% of patients and controls respectively. After adjusting for age, gender, ethnicity, BMI and hydrocortisone dose per metre square of body surface area in patients, there were no significant metabolic associations with this polymorphism and hydrocortisone doses were not higher in patients with the polymorphism. This study did not identify any associations between the 9β polymorphism and cardiovascular risk factors or hydrocortisone dose and determination of this polymorphism is therefore unlikely to be of clinical benefit in the management of patients with AD.

Methylenetetrahydrofolate Reductase Gene Polymorphism (C677T) as a Risk Factor for Arterial Thrombosis in Georgian Patients.

PubMed

Garakanidze, Sopio; Costa, Elísio; Bronze-Rocha, Elsa; Santos-Silva, Alice; Nikolaishvili, Giorgi; Nakashidze, Irina; Kakauridze, Nona; Glonti, Salome; Khukhunaishvili, Rusudan; Koridze, Marina; Ahmad, Sarfraz

2018-01-01

Methylenetetrahydrofolate reductase ( MTHFR) gene polymorphism (C677T)] is a well-recognized genetic risk factor for venous thrombosis; however, its association with arterial thrombosis is still under debate. Herein, we evaluated the prevalence of MTHFR C677T polymorphism in Georgian patients in comparison with healthy individuals and its association with arterial thrombosis. We enrolled 214 participants: 101 with arterial thrombosis (71.3% males; mean age: 66.3 ± 12.1 years) and 113 controls (67.3% males; mean age: 56.6 ± 11.3 years). Genomic DNA was extracted from dry blood spot on Whatman filter paper. Polymerase chain reaction was performed to determine MTHFR C677T polymorphism. Frequency of C677T allele polymorphism in controls was 21.2%, which corresponded to heterozygous and homozygous stage frequencies of 35.4% and 3.5%, respectively. In patient group, an allelic frequency of 33.2% was found, which corresponded to the presence of 48.5% of heterozygous and 8.9% of homozygous individuals. Comparing the frequency of mutated alleles between the 2 groups, a significantly high frequency of mutated alleles was found in patient group ( P < .05). In conclusion, high frequency of MTHFR C677T polymorphism found in arterial thrombosis patient group suggests that this polymorphism might increase the risk of arterial thrombosis in Georgian patients.

Interleukin-21 gene polymorphism rs2221903 is associated with disease activity in patients with rheumatoid arthritis.

PubMed

Malinowski, Damian; Paradowska-Gorycka, Agnieszka; Safranow, Krzysztof; Pawlik, Andrzej

2017-08-01

Interleukin-21 (IL-21) is a cytokine which plays a significant role in the pathogenesis and disease activity of rheumatoid arthritis (RA). Genetic polymorphisms in the IL-21 gene may alter the synthesis of IL-21. The aim of this study was to examine IL-21 and IL-21R polymorphisms in patients with RA. We examined 422 patients with RA and 338 healthy controls. Single nucleotide polymorphisms (SNPs) within the IL-21 (rs6822844 G>T, rs6840978 C>T, rs2221903 T>C) and IL-21R (rs2285452 G>A) genes were genotyped using TaqMan genotyping assays. There were no statistically significant differences in the distribution of studied genotypes and alleles between RA patients and the control group. To examine whether IL-21 polymorphisms affect disease activity in RA patients, we compared the distribution of IL-21 genotypes between patients with DAS28 ≤ 2.5 (patients with remission of disease symptoms) and patients with DAS28 > 2.5 (patients with active RA). Among patients with DAS28 > 2.5, increased prevalence of rs2221903 CT and CC genotypes was observed (OR = 1.54; 95% CI: 1.04-2.28; p = 0.035). The results of this study suggest that IL-21 and IL-21R gene polymorphisms are not risk loci for RA susceptibility, whereas the IL-21 rs2221903 polymorphism is associated with disease activity.

Prevalence of Hb S (HHB: c.20A > T) in a Honduran population of African descent.

PubMed

Erazo, Brian M; Ramírez, Gilberto A; Cerrato, Linda E; Pinto, Luis J; Castro, Edder J; Yanez, Néstor J; Montoya, Brayan; Fontecha, Gustavo A

2015-01-01

Sickle cell disease is the most common hemoglobinopathy worldwide, particularly in Africa and among people of African descent. Serious clinical consequences characterize the homozygous condition. To determine the prevalence of Hb S (HBB: c.20A > T) and anemia in a community of people of African descent from Honduras, 202 individuals were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The high prevalence found indicates that it is necessary to implement a program to prevent the consequences of this disease in vulnerable populations of Honduras.

Prevalence and genotype identification of Toxoplasma gondii in wild animals from southwestern Spain.

PubMed

Calero-Bernal, Rafael; Saugar, José M; Frontera, Eva; Pérez-Martín, Juan E; Habela, Miguel A; Serrano, Francisco J; Reina, David; Fuentes, Isabel

2015-01-01

We used PCR to detect Toxoplasma gondii in the principal game species in southwestern Spain. We detected T. gondii in 32.2% of animals tested. Prevalences varied from 14.7% in wild boar (Sus scrofa) to 51.2% in red fox (Vulpes vulpes). The most prevalent genotype was type II (50.0%), followed by type III (20.6%) and type I (5.9%). Mixed infections (11.8%) were detected in wild boar (types I+III) and red fox (types II+III). Polymorphic strains (11.8%) were detected in several species. The high prevalence and the genetic variability shown could have implications for infection of farm animals and humans.

The Helicobacter pylori duodenal ulcer promoting gene, dupA in China.

PubMed

Zhang, Zhiyu; Zheng, Qing; Chen, Xiaoyu; Xiao, Shudong; Liu, Wenzhong; Lu, Hong

2008-10-25

The prevalence of H. pylori is as high as 60-70% in Chinese population. Although duodenal ulcer and gastric cancer are both caused by H. pylori, they are at opposite ends of the spectrum and as such are considered mutually exclusive. Duodenal ulcer promoting (dupA) gene was reported to be associated with duodenal ulcer development. The aim of this study was to determine the prevalence of dupA gene of Helicobacter pylori in patients with various gastroduodenal diseases and to explore the association between the gene and other virulence factors. H. pylori were isolated from gastric biopsies of patients with chronic gastritis, duodenal ulcer (DU), gastric ulcer (GU), or non-cardia gastric carcinoma. The dupA, cagA, vacA, iceA and babA2 genotypes were determined by polymerase chain reaction. Histological features of gastric mucosal biopsy specimens were graded based on the scoring system proposed by the updated Sydney system. IL-1beta polymorphism was investigated using restriction fragment length polymorphism. Isolates from 360 patients including 133 with chronic gastritis, 101 with DU, 47 with GU, and 79 with non-cardia gastric carcinoma were examined. The dupA gene was detected in 35.3% (127/360) and the prevalence DU patients was significantly greater than that in gastric cancer or GU patients (45.5% vs. 24.1% and 23.4%, P < 0.05). Patients infected with dupA-positive strains had higher scores for chronic inflammation compared to those with dupA-negative strains (2.36 vs. 2.24, p = 0.058). The presence of dupA was not associated with the cagA, vacA, iceA and babA 2 genotypes or with IL-1beta polymorphisms. In China the prevalence of dupA gene was highest in DU and inversely related to GU and gastric cancer.

High prevalence of anaemia among African migrants in Germany persists after exclusion of iron deficiency and erythrocyte polymorphisms.

PubMed

Müller, Sophie A; Amoah, Stephen K B; Meese, Stefanie; Spranger, Joachim; Mockenhaupt, Frank P

2015-09-01

Haematological parameters differ between individuals of African and European ancestry. However, respective data of first-generation African migrants are virtually absent. We assessed these in Ghanaian migrants living in Berlin, compared them with reference data from Germany and Ghana, and estimated the role of iron deficiency (ID) and erythrocyte polymorphisms in anaemia. A total of 576 Ghanaians (median age, 45 years) were analysed. Blood counts were performed, haemoglobinopathies and glucose-6-phosphate dehydrogenase (G6PD) deficiency were genotyped, and concentrations of ferritin and C-reactive protein were measured to define ID. Most individuals had resided in Germany for more than a decade (median, 18 years). By WHO definition, anaemia was present in 30.9% of females and 9.4% of males. Median haemoglobin (Hb) levels were lower than among Germans (women, -0.8 g/dl, men, -0.7 g/dl). However, applying reference values from Ghana, only 1.9% of the migrants were considered anaemic. Alpha-thalassaemia, Hb variants and G6PD deficiency were observed in 33.9%, 28.3% and 23.6%, respectively. ID was highly prevalent in women (32.0%; men, 3.9%). The population fraction of anaemia cases attributable to ID was 29.0% (alpha-thalassaemia, 13.6%; G6PD deficiency, 13.5%). Nevertheless, excluding ID, alpha-thalassaemia, G6PD deficiency and sickle cell disease, anaemia prevalence remained high (women, 18.4%; men, 6.5%), and was also high when applying uncensored thresholds proposed for African Americans (females, 19.3%; males, 7.8%). Iron deficiency and erythrocyte polymorphisms are common among first-generation Ghanaian migrants but explain only part of the increased prevalence of anaemia. Common Hb thresholds for the definition of anaemia may not be appropriate for this group. © 2015 John Wiley & Sons Ltd.

The Helicobacter pylori duodenal ulcer promoting gene, dupA in China

PubMed Central

Zhang, Zhiyu; Zheng, Qing; Chen, Xiaoyu; Xiao, Shudong; Liu, Wenzhong; Lu, Hong

2008-01-01

Background The prevalence of H. pylori is as high as 60–70% in Chinese population. Although duodenal ulcer and gastric cancer are both caused by H. pylori, they are at opposite ends of the spectrum and as such are considered mutually exclusive. Duodenal ulcer promoting (dupA) gene was reported to be associated with duodenal ulcer development. The aim of this study was to determine the prevalence of dupA gene of Helicobacter pylori in patients with various gastroduodenal diseases and to explore the association between the gene and other virulence factors. Methods H. pylori were isolated from gastric biopsies of patients with chronic gastritis, duodenal ulcer (DU), gastric ulcer (GU), or non-cardia gastric carcinoma. The dupA, cagA, vacA, iceA and babA2 genotypes were determined by polymerase chain reaction. Histological features of gastric mucosal biopsy specimens were graded based on the scoring system proposed by the updated Sydney system. IL-1β polymorphism was investigated using restriction fragment length polymorphism. Results Isolates from 360 patients including 133 with chronic gastritis, 101 with DU, 47 with GU, and 79 with non-cardia gastric carcinoma were examined. The dupA gene was detected in 35.3% (127/360) and the prevalence DU patients was significantly greater than that in gastric cancer or GU patients (45.5% vs. 24.1% and 23.4%, P < 0.05). Patients infected with dupA-positive strains had higher scores for chronic inflammation compared to those with dupA-negative strains (2.36 vs. 2.24, p = 0.058). The presence of dupA was not associated with the cagA, vacA, iceA and babA 2 genotypes or with IL-1β polymorphisms. Conclusion In China the prevalence of dupA gene was highest in DU and inversely related to GU and gastric cancer. PMID:18950522

Pharmacogenetics of drug-metabolizing enzymes in US Hispanics

PubMed Central

Duconge, Jorge; Cadilla, Carmen L.; Ruaño, Gualberto

2015-01-01

Although the Hispanic population is continuously growing in the United States, they are underrepresented in pharmacogenetic studies. This review addresses the need for compiling available pharmacogenetic data in US Hispanics, discussing the prevalence of clinically relevant polymorphisms in pharmacogenes encoding for drug-metabolizing enzymes. CYP3A5*3 (0.245–0.867) showed the largest frequency in a US Hispanic population. A higher prevalence of CYP2C9*3, CYP2C19*4, and UGT2B7 IVS1+985 A>Gwas observed in US Hispanic vs. non-Hispanic populations. We found interethnic and intraethnic variability in frequencies of genetic polymorphisms for metabolizing enzymes, which highlights the need to define the ancestries of participants in pharmacogenetic studies. New approaches should be integrated in experimental designs to gain knowledge about the clinical relevance of the unique combination of genetic variants occurring in this admixed population. Ethnic subgroups in the US Hispanic population may harbor variants that might be part of multiple causative loci or in linkage-disequilibrium with functional variants. Pharmacogenetic studies in Hispanics should not be limited to ascertain commonly studied polymorphisms that were originally identified in their parental populations. The success of the Personalized Medicine paradigm will depend on recognizing genetic diversity between and within US Hispanics and the uniqueness of their genetic backgrounds. PMID:25431893

The transcobalamin codon 259 polymorphism influences the risk of human spontaneous abortion.

PubMed

Zetterberg, H; Regland, B; Palmér, M; Rymo, L; Zafiropoulos, A; Arvanitis, D A; Spandidos, D A; Blennow, K

2002-12-01

The remethylation cycle of methionine is folate and vitamin B(12) (cobalamin) dependent and appears to be crucial for embryonic development, probably through effects on synthesis of DNA, proteins and polyamines. Transcobalamin (TC) transports vitamin B(12) to the tissues. The objective of the present investigation was to explore the putative association between the major TC genetic polymorphism (Pro259Arg) and human spontaneous abortion. The prevalence of the TC Pro259Arg polymorphism was determined in DNA samples from embryos that had been spontaneously aborted between the 6th and 20th week after conception, and adult controls using solid-phase minisequencing technique. The 259-Pro allele was significantly less frequent in the spontaneous abortion group than in the control group (42.2 and 57.0% respectively; P = 0.005), while the frequency of 259-Arg was significantly increased. There was a lower prevalence of 259-Pro homozygotes in the spontaneous abortion group compared with the control group (9.1 and 32.2% respectively; P < 0.001). The 259-Pro allele seems to have beneficial influences during embryogenesis, conceivably through its positive effect on vitamin B(12) intracellular bioavailability. Our results warrant additional investigations addressing the question if vitamin B(12) supplementation in addition to folic acid supplementation may prevent spontaneous abortion in women planning a pregnancy.

Constituents and secondary metabolite natural products in fresh and deteriorated cassava roots.

PubMed

Bayoumi, Soad A L; Rowan, Michael G; Beeching, John R; Blagbrough, Ian S

2010-04-01

A phytochemical analysis of cassava (Manihot esculenta Crantz) fresh roots and roots suffering from post-harvest physiological deterioration (PPD) has been carried out. The first isolation and identification of galactosyl diacylglycerides from fresh cassava roots is reported, as well as beta-carotene, linamarin, and beta-sitosterol glucopyranoside. The hydroxycoumarin scopoletin and its glucoside scopolin were identified from cassava roots during PPD, as well as trace quantities of esculetin and its glucoside esculin. There is no isoscopoletin in cassava roots during PPD. Copyright 2009 Elsevier Ltd. All rights reserved.

Polymorphism of antibiotic-inactivating enzyme driven by ecology expands the environmental resistome.

PubMed

Kim, Dae-Wi; Thawng, Cung Nawl; Choi, Jung-Hye; Lee, Kihyun; Cha, Chang-Jun

2018-01-01

The environmental resistome has been recognized as the origin and reservoir of antibiotic resistance genes and considered to be dynamic and ever expanding. In this study, a targeted gene sequencing approach revealed that the polymorphic diversity of the aminoglycoside-inactivating enzyme AAC(6')-Ib was ecological niche-specific. AAC(6')-Ib-cr, previously known as a clinical variant, was prevalent in various soils and the intestines of chickens and humans, suggesting that this variant might not have arisen from adaptive mutations in the clinic but instead originated from the environment. Furthermore, ecologically dominant polymorphic variants of AAC(6')-Ib were characterized and found to display different substrate specificities for quinolones and aminoglycosides, conferring the altered resistance spectra. Interestingly, a novel variant with the D179Y substitution showed an extended resistance spectrum to the recently developed fluoroquinolone gemifloxacin. Our results suggest that soil and animal microbiomes could be major reservoirs of antibiotic resistance; polymorphic diversity expands the antibiotic resistome in the environment, resulting in the potential emergence of novel resistance.

Lack of association between deletion polymorphism of BIM gene and in vitro drug sensitivity in B-cell precursor acute lymphoblastic leukemia.

PubMed

Huang, Meixian; Miyake, Kunio; Kagami, Keiko; Abe, Masako; Shinohara, Tamao; Watanabe, Atsushi; Somazu, Shinpei; Oshiro, Hiroko; Goi, Kumiko; Goto, Hiroaki; Minegishi, Masayoshi; Iwamoto, Shotaro; Kiyokawa, Nobutaka; Sugita, Kanji; Inukai, Takeshi

2017-09-01

A deletion polymorphism in the BIM gene was identified as an intrinsic mechanism for resistance to tyrosine kinase inhibitor in chronic myeloid leukemia patients in East Asia. BIM is also involved in the responses to glucocorticoid and chemotherapy in acute lymphoblastic leukemia (ALL), suggesting a possible association between deletion polymorphism of BIM and the chemosensitivity of ALL. Thus, we analyzed 72 B-cell precursor (BCP)-ALL cell lines established from Japanese patients. Indeed, higher BIM gene expression was associated with good in vitro sensitivities to glucocorticoid and chemotherapeutic agents used in induction therapy. We also analyzed the methylation status of the BIM gene promoter by next generation sequencing of genome bisulfite PCR products, since genetic polymorphism could be insignificant when epigenetically inactivated. Hypermethylation of the BIM gene promoter was associated with lower BIM gene expression and poorer sensitivity to vincristine. Of note, however, the prevalence of a deletion polymorphism was not associated with the BIM gene expression level or drug sensitivities in BCP-ALL cell lines, in which the BIM gene was unmethylated. These observations suggest that an association of a deletion polymorphism of BIM and the response to induction therapy in BCP-ALL may be clinically minimal. Copyright © 2017. Published by Elsevier Ltd.

3'-UTR Polymorphisms of MTHFR and TS Associated with Osteoporotic Vertebral Compression Fracture Susceptibility in Postmenopausal Women.

PubMed

Ahn, Tae-Keun; Kim, Jung Oh; Kim, Hyun Woo; Park, Han Sung; Shim, Jeong Hyun; Ropper, Alexander E; Han, In Bo; Kim, Nam Keun

2018-03-12

Postmenopausal osteoporosis is one of the most prominent diseases in postmenopausal women and it is increasing in prevalence with the aging population. Furthermore, osteoporosis and osteoporotic vertebral compression fractures (OVCFs) are related to mortality and decreased quality of life. Therefore, searching for biomarkers that are able to identify postmenopausal women who are at high risk of developing OVCFs is an effective strategy for improving the quality of life of patients and alleviating social and economic burdens. In this study, we investigated methylenetetrahydrofolate reductase ( MTHFR ) and thymidylate synthase ( TS ) gene polymorphisms in postmenopausal women with OVCF. We recruited 301 postmenopausal women and performed genotyping for the presence of MTHFR 2572C>A, 4869C>G and TS 1100C>T, 1170A>G. Genotyping was analyzed using the polymerization chain reaction restriction fragment length polymorphism assay. MTHFR 2572C>A and TS 1100C>T were associated with the prevalence of osteoporosis (MTHFR 2572CC versus CA+AA: odd ratio [OR] adjusted age, hypertention [HTN], and diabetes mellitus [DM] = 0.49, p = 0.012) and the occurrence of OVCFs (MTHFR 2572CC versus CA+AA: OR adjusted age, HTN, and DM = 0.38, p = 0.013; TS 1100CC versus CT+TT: OR adjusted age, HTN, and DM = 0.46, p = 0.02). Our novel finding is the identification of MTHFR and TS genetic variants that decrease susceptibility to OVCFs. Our findings suggest that polymorphisms in the MTHFR and TS genes are associated with susceptibility to osteoporosis and OVCFs in postmenopausal women.

The effects of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 gene on glucose/insulin metabolism interact with prenatal exposure to famine.

PubMed

de Rooij, Susanne R; Painter, Rebecca C; Phillips, David I W; Osmond, Clive; Tanck, Michael W T; Defesche, Joep C; Bossuyt, Patrick M M; Michels, Robert P J; Bleker, Otto P; Roseboom, Tessa J

2006-05-01

An adverse fetal environment may permanently modify the effects of specific genes on glucose tolerance, insulin secretion, and insulin sensitivity. In the present study, we assessed a possible interaction of the peroxisome proliferator-activated receptor (PPAR)-gamma2 Pro12Ala polymorphism with prenatal exposure to famine on glucose and insulin metabolism. We measured plasma glucose and insulin concentrations after an oral glucose tolerance test and determined the PPAR-gamma2 genotype among 675 term singletons born around the time of the 1944-1945 Dutch famine. A significant interaction effect between exposure to famine during midgestation and the PPAR-gamma2 Pro12Ala polymorphism was found on the prevalence of impaired glucose tolerance and type 2 diabetes. The Ala allele of the PPAR-gamma2 gene was associated with a higher prevalence of impaired glucose tolerance and type 2 diabetes but only in participants who had been prenatally exposed to famine during midgestation. Similar interactions were found for area under the curve for insulin and insulin increment ratio, which were lower for Ala carriers exposed to famine during midgestation. The effects of the PPAR-gamma2 Pro12Ala polymorphism on glucose and insulin metabolism may be modified by prenatal exposure to famine during midgestation. This is possibly due to a combined deficit in insulin secretion, as conferred by pancreatic beta-cell maldevelopment and carrier type of the Ala allele in the PPAR-gamma2 gene.

ALDH2 polymorphism and alcohol-related cancers in Asians: a public health perspective.

PubMed

Chang, Jeffrey S; Hsiao, Jenn-Ren; Chen, Che-Hong

2017-03-03

The occurrence of more than 200 diseases, including cancer, can be attributed to alcohol drinking. The global cancer deaths attributed to alcohol-consumption rose from 243,000 in 1990 to 337,400 in 2010. In 2010, cancer deaths due to alcohol consumption accounted for 4.2% of all cancer deaths. Strong epidemiological evidence has established the causal role of alcohol in the development of various cancers, including esophageal cancer, head and neck cancer, liver cancer, breast cancer, and colorectal cancer. The evidence for the association between alcohol and other cancers is inconclusive. Because of the high prevalence of ALDH2*2 allele among East Asian populations, East Asians may be more susceptible to the carcinogenic effect of alcohol, with most evidence coming from studies of esophageal cancer and head and neck cancer, while data for other cancers are more limited. The high prevalence of ALDH2*2 allele in East Asian populations may have important public health implications and may be utilized to reduce the occurrence of alcohol-related cancers among East Asians, including: 1) Identification of individuals at high risk of developing alcohol-related cancers by screening for ALDH2 polymorphism; 2) Incorporation of ALDH2 polymorphism screening into behavioral intervention program for promoting alcohol abstinence or reducing alcohol consumption; 3) Using ALDH2 polymorphism as a prognostic indicator for alcohol-related cancers; 4) Targeting ALDH2 for chemoprevention; and 5) Setting guidelines for alcohol consumption among ALDH2 deficient individuals. Future studies should evaluate whether these strategies are effective for preventing the occurrence of alcohol-related cancers.

Tailoring Nutritional Advice for Mexicans Based on Prevalence Profiles of Diet-Related Adaptive Gene Polymorphisms

PubMed Central

Ojeda-Granados, Claudia; Panduro, Arturo; Gonzalez-Aldaco, Karina; Sepulveda-Villegas, Maricruz; Rivera-Iñiguez, Ingrid

2017-01-01

Diet-related adaptive gene (DRAG) polymorphisms identified in specific populations are associated with chronic disorders in carriers of the adaptive alleles due to changes in dietary and lifestyle patterns in recent times. Mexico’s population is comprised of Amerindians (AM) and Mestizos who have variable AM, European (EUR) and African genetic ancestry and an increased risk of nutrition-related chronic diseases. Nutritional advice based on the Mexican genome and the traditional food culture is needed to develop preventive and therapeutic strategies. Therefore, we aimed to provide a prevalence profile of several DRAG polymorphisms in the Mexican population, including Central West (CW) Mexico subpopulations. Geographic heat maps were built using ArcGIS10 (Esri, Redlands, CA, USA) software, based on the published data of the MTHFR C677T (rs1801133), ABCA1 Arg230Cys (rs9282541), APOE T388C (rs429358)/C526T (rs7412), LCT C-13910T (rs4988235) polymorphisms and AMY1 copy number variation (CNV). Also, new data obtained by allelic discrimination-real-time polymerase chain reaction (RT-PCR) assays for the MTHFR, ABCA1, and APOE polymorphisms as well as the AMY1 CNV in the CW Mexico subpopulations with different proportions of AM and EUR ancestry were included. In the CW region, the highest frequency of the MTHFR 677T, ABCA1 230C and APOE ε4 adaptive alleles was observed in the AM groups, followed by Mestizos with intermediate AM ancestry. The LCT-13910T allele frequency was highest in Mestizos-EUR but extremely low in AM, while the AMY1 diploid copy number was 6.82 ± 3.3 copies. Overall, the heat maps showed a heterogeneous distribution of the DRAG polymorphisms, in which the AM groups revealed the highest frequencies of the adaptive alleles followed by Mestizos. Given these genetic differences, genome-based nutritional advice should be tailored in a regionalized and individualized manner according to the available foods and Mexican traditional food culture that may lead to a healthier dietary pattern. PMID:29125573

Methylene tetrahydrofolate reductase gene polymorphism in Egyptian children with acute lymphoblastic leukemia.

PubMed

Tantawy, Azza A G; El-Bostany, Eman A; Adly, Amira A M; Abou El Asrar, Mohammed; El-Ghouroury, Eman A; Abdulghaffar, Esmat E

2010-01-01

Genetic variations of the enzymes involved in chemotherapy metabolism in cancer patients may play a role in determining relapse and toxicity risks. Methotrexate is a key drug in acute lymphoblastic leukemia (ALL) treatment; it inhibits DNA replication by blocking the conversion of 5,10 methylene tetrahydrofolate to 5-methylene tetrahydrofolate by methylene tetrahydrofolate reductase (MTHFR). MTHFR is central to folate metabolism and has two common functional polymorphisms (C677>T and A1298>C). The present study aimed to assess the prevalence of MTHFR polymorphisms C677>T and A1298>C in Egyptian children with ALL and the relation to the frequency of drug-induced complications and relapse rate. Forty ALL patients were included in the study. They were treated according to modified ALL-BFM 90 protocol, and were followed up for 3.1-6.5 years. The severity and duration of hepatic, mucosal and infectious complications during therapy were reported. MTHFR genotyping was done with a PCR-based restriction fragment length polymorphism assay. The MTHFR C677>T polymorphic allele frequencies were 40, 27.5, and 32.5% for TT, CT, and CC genotypes, respectively among the studied ALL patients. The MTHFR A1298>C polymorphic allele frequencies were 40, 35, and 25% for AA, AC, and CC genotypes, respectively. Methotrexate therapy was significantly associated with increased grade III/IV toxicity in TT genotype: diarrhea in 81.3%, oral mucositis in 81.3%, elevated transaminases in 87.5%, neutropenia in 78.7% compared to values of 7.7, 7.7, 15.3, and 7.7% in CC genotype, respectively (P < 0.0001, P < 0.0001, P < 0.0001, and P = 0.03). The 677 TT genotype was significantly associated with relapse in 5 years in 56.3%, compared to 18.2% in CT and 0% in CC alleles. The overall 5 years survival was significantly lower in 677 TT (50%) compared with CC genotypes (92.3%) (P = 0.001). No significant relation was found between MTHFR A1298C polymorphism and the risks of therapy induced complications or relapse rate in the studied ALL patients. MTHFR TT genotype is significantly associated with increased mucosal and hepatic toxicity during methotrexate therapy as well as increased relapse rate in childhood ALL. Because of the relatively high prevalence of the TT genotype in the studied Egyptian children with ALL, MTHFR gene polymorphisms should be studied in large multicenter studies; and dosage modification of methotrexate in the ALL treatment protocols should be considered based on the MTHFR gene pattern.

Frequency of genetic polymorphisms of PXR gene in the Brazilian population.

PubMed

Moreira, Ricardo P P; Jorge, Alexander A L; Mendonca, Berenice B; Bachega, Tânia A S S

2011-01-01

PXR polymorphisms have been implicated in modulating CYP3A4 and PXR expression, potentially accounting for interindividual differences in drug metabolism. The prevalence of PXR polymorphisms varies among ethnic groups and data on the allelic distribution in the highly mixed Brazilian population is lacking. The aim of this study was to analyze genetic variations in the PXR gene in Brazilians and to compare the results to other ethnic groups. DNA samples from 117 healthy Brazilians underwent PCR amplification and sequencing. Eleven polymorphisms were identified, 3 of which are highly associated with differences in CYP3A4 expression. We also identified 1 new synonymous variant in 1.3% of the alleles. Among the functional polymorphisms, -25913 C>T and -6994T>C occurred at a higher frequency comparedtothe Africanalleles (p < 0.05) but at a lower frequency compared to Caucasian alleles. The 8055 C>T allele was found at a similar frequency to those described in Caucasians and Africans (p > 0.05). We observed that functional variants of the PXR were frequent in our sample of the Brazilian population. Our results suggest that PXR gene variants may be of interest in pharmacogenetic studies involving Brazilians.

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.

Polymorphisms in ERAP1 and ERAP2 are shared by Caninae and segregate within and between random- and pure-breeds of dogs.

PubMed

Pedersen, N C; Dhanota, J K; Liu, H

2016-10-15

Specific polymorphisms in the endoplasmic reticulum amino peptidase genes ERAP1 and ERAP2, when present with certain MHC class receptor types, have been associated with increased risk for specific cancers, infectious diseases and autoimmune disorders in humans. This increased risk has been linked to distinct polymorphisms in both ERAPs and MHC class I receptors that affect the way cell-generated peptides are screened for antigenicity. The incidence of cancer, infectious disease and autoimmune disorders differ greatly among pure breeds of dogs as it does in humans and it is possible that this heightened susceptibility is also due to specific polymorphisms in ERAP1 and ERAP2. In order to determine if such polymorphisms exist, the ERAP1 and ERAP2 genes of 10 dogs of nine diverse breeds were sequenced and SNPs causing synonymous or non-synonymous amino acid changes, deletions or insertions were identified. Eight ERAP1 and 10 ERAP2 SNPs were used to create a Sequenom MassARRAY iPLEX based test panel which defined 24 ERAP1, 36 ERAP2 and 128 ERAP1/2 haplotypes. The prevalence of these haplotypes was then measured among dog, wolf, coyote, jackal and red fox populations. Some haplotypes were species specific, while others were shared across species, especially between dog, wolf, coyote and jackal. The prevalence of these haplotypes was then compared among various canid populations, and in particular between various populations of random- and pure-bred dogs. Human-directed positive selection has led to loss of ERAP diversity and segregation of certain haplotypes among various dog breeds. A phylogenetic tree generated from 45 of the most common ERAP1/2 haplotypes demonstrated three distinct clades, all of which were rooted with haplotypes either shared among species or specific to contemporary dogs, coyote and wolf. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Prevalence of alpha actinin-3 gene (ACTN3) R577X and angiotensin converting enzyme (ACE) insertion / deletion gene polymorphisms in national and amateur Turkish athletes.

PubMed

Eroğlu, Onur; Zileli, Rayif; Nalbant, M Ali; Ulucan, Korkut

2018-04-30

Studies to date showed the importance of alpha- actinin-3 (ACTN3) R577X and angiotensin converting enzyme (ACE) ID polymorphisms on determining athletic performance. Therefore, in this study, we aimed to examine polymorphisms given to Turkish athletes and compare them with sedentary individuals. Genomic DNAs were extracted from peripheral blood by using commercially available DNA isolation kit (Macherey-Nagel, NucleoSpin®, Germany). For this study, a total of 84 volunteers (23 national athletes, 27 amateur athletes and 34 sedentary controls) was recruited.  ACE ID genotypes were determined by conventional polymerase chain reaction, and ACTN3 R577X polymorphisms by polymerase chain reaction- restriction fragment length polymorphism methodology.   In ACTN3 R577X polymorphism, RX was the dominating genotype, and we detected no RR genotype in national athletes. (no RR genotype was detected in national athletes) X allele is more frequent in national athletes and R allele was more frequent in both amateur athletes and control group. II genotype was more frequent in national athletes and in control group, whereas DD genotype was more frequent in amateur athletes for ACE ID polymorphism. When we consider alleles, D allele was found more frequently in amateur athletes and control group whereas I allele was more frequent in national athletes in ACE ID polymorphism. For ACTN3, X allele was superior to R allele. ACTN3 R577X and ACE ID polymorphisms were important biomarkers in determining athletic performance. However, our results in Turkish athletes suggest that ACE D allele and ACTN3 X alleles may be beneficial to athletes potentially, regardless of the distance they perform.

Toll-like receptor 4 gene polymorphism modulates phenotypic expression in patients with hereditary hemochromatosis.

PubMed

Krayenbuehl, Pierre-Alexandre; Hersberger, Martin; Truninger, Kaspar; Müllhaupt, Beat; Maly, Friedrich E; Bargetzi, Mario; Schulthess, Georg

2010-07-01

Clinical penetrance of hereditary hemochromatosis is highly variable. We hypothesized that it might be modified by factors involved in the cellular immune response, such as toll-like receptors (TLRs) or nucleotide oligomerization domain proteins (NODs). Clinical expression of hemochromatosis was assessed as a function of TLR4, TLR9, and NOD2 polymorphisms in 99 homozygous carriers of the HFE C282Y mutation with mild-to-severe iron overload. Thirteen (13%) of the 99 hemochromatosis patients were heterozygous for a TLR4 Asp299Gly polymorphism and 86 (87%) were TLR4 wild-type-only carriers. Clinical expression of hemochromatosis was observed more frequently in carriers of the TLR4 polymorphism (100%) than in TLR4 wild-type carriers (56%, P = 0.002). This was based on higher prevalences of liver disease (92 vs. 45%, P = 0.002) and arthropathy of metacarpophalangeal joints (69 vs. 35%, P = 0.018) in TLR4 polymorphism carriers. The finding was strengthened by the strong association of TLR4 polymorphism with liver fibrosis in the subgroup of 52 patients who underwent a liver biopsy (P = 0.011). The TLR4 polymorphism did, however, not correlate with body iron overload. The study results remained significant in multiple regression analyses after excluding possible confounding effects, such as age, sex, alcohol, or meat intake, and in the subgroup of 84 patients presenting as the first members of their families. TLR4 Asp299Gly polymorphism modulates clinical expression in patients with hereditary hemochromatosis. The polymorphism does not correlate with iron overload suggesting that TLR4 plays a role in an inflammatory process arising from toxic effects of iron accumulation.

Genetic polymorphisms in Plasmodium falciparum chloroquine resistance genes, pfcrt and pfmdr1, in North Sulawesi, Indonesia.

PubMed

Reteng, Patrick; Vrisca, Visia; Sukarno, Inka; Djarkoni, Ilham Habib; Kalangi, Jane Angela; Jacobs, George Eduardo; Runtuwene, Lucky Ronald; Eshita, Yuki; Maeda, Ryuichiro; Suzuki, Yutaka; Mongan, Arthur Elia; Warouw, Sarah Maria; Yamagishi, Junya; Tuda, Josef

2017-04-04

Malaria still poses one of the major threats to human health. Development of effective antimalarial drugs has decreased this threat; however, the emergence of drug-resistant Plasmodium falciparum, a cause of Malaria, is disconcerting. The antimalarial drug chloroquine has been effectively used, but resistant parasites have spread worldwide. Interestingly, the withdrawal of the drug reportedly leads to an increased population of susceptible parasites in some cases. We examined the prevalence of genomic polymorphisms in a malaria parasite P. falciparum, associated with resistance to an antimalarial drug chloroquine, after the withdrawal of the drug from Indonesia. Blood samples were collected from 95 malaria patients in North Sulawesi, Indonesia, in 2010. Parasite DNA was extracted and analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for pfcrt and pfmdr1. In parallel, multiplex amplicon sequencing for the same genes was carried out with Illumina MiSeq. Of the 59 cases diagnosed as P. falciparum infection by microscopy, PCR-RFLP analysis clearly identified the genotype 76T in pfcrt in 44 cases. Sequencing analysis validated the identified genotypes in the 44 cases and demonstrated that the haplotype in the surrounding genomic region was exclusively SVMNT. Results of pfmdr1 were successfully obtained for 51 samples, where the genotyping results obtained by the two methods were completely consistent. In pfmdr1, the 86Y mutant genotype was observed in 45 cases (88.2%). Our results suggest that the prevalence of the mutated genotypes remained dominant even 6 years after the withdrawal of chloroquine from this region. Diversified haplotype of the resistance-related locus, potentially involved in fitness costs, unauthorized usage of chloroquine, and/or a short post-withdrawal period may account for the observed high persistence of prevalence.

High prevalence of dengue antibodies and the arginine variant of the FcγRIIa polymorphism in asymptomatic individuals in a population of Minas Gerais State, Southeast Brazil.

PubMed

Pereira, Anna Carolina Toledo da Cunha; de Siqueira, Tatiane Ribeiro; de Oliveira Prado, Andressa Anunciação; da Silva, Camila Almeida Veiga; de Fátima Silva Moraes, Thaís; Aleixo, Alan Alex; de Magalhaes, José Carlos; de Souza, Gabriel Augusto Pires; Drumond, Betânia Paiva; Ferreira, Gustavo Portela; de Mello Silva, Breno; de Brito Magalhães, Cintia Lopes; Santos, Luciana Lara; Ferreira, Jaqueline Maria Siqueira; Malaquias, Luiz Cosme Cotta; Coelho, Luiz Felipe Leomil

2018-06-01

Dengue is the most prevalent arthropod-borne viral illness in humans worldwide. Single-nucleotide polymorphisms (SNPs) in genes involved in the immune response, such as dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), IgG Fc receptor II-A (FcγRIIa), vitamin D receptor (VDR), and tumor necrosis factor alpha (TNF-α), were previously reported to be associated with susceptibility to dengue disease in different human populations. Therefore, due to the relevant association of host immune and genetic status with disease susceptibility/severity of dengue, this work aims to verify the frequency of anti-dengue virus antibodies and some dengue-associated risk SNPs in a population in Minas Gerais State, Southeast Brazil. A total of 1560 individuals were genotyped for polymorphisms in DC-SIGN (rs4804803), FcγRIIa (rs1801274), VDR (rs7975232), and TNF-α (rs1800629). The presence of anti-dengue antibodies (IgM and/or IgG) in these samples was also assayed. Anti-dengue antibodies were detected at an overall frequency of 16.86%, indicating a virus infection in asymptomatic individuals. The genotypic frequencies of all SNPs studied did not differ between the asymptomatic and control groups. Regarding the allelic frequencies of the four SNPs analyzed, a higher frequency was detected of the G allele of FcγRIIa/rs1801274 in the asymptomatic individuals when compared to that in the control group (p = 0.03). Therefore, the results showed a high prevalence of asymptomatic individuals in Minas Gerais State, with a potential association between the presence of the G allele of FcγRIIa/rs1801274 and protection against symptomatic disease.

Relations of blood pressure to angiotensinogen gene T174M polymorphism and alcohol intake.

PubMed

Takashima, Yutaka; Kokaze, Akatsuki; Matsunaga, Naomi; Yoshida, Masao; Sekiguchi, Kanako; Sekine, Yasuko; Sumiya, Yu

2003-07-01

To clarify the interactive effects of alcohol intake and angiotensinogen gene codon 174 (T174M) polymorphisms on blood pressure in Japanese male workers. On the basis of data from health examinations, nutrition survey and T174M genotype analysis conducted for 185 Japanese male workers at 2000, the prevalence of high-normal blood pressure (HNBP) and hypertension were compared between the four subgroups crossed by two T174M genotype categories ('TT' type, and 'TM or MM' type) and two alcohol intake categories (less than 13.7 g per day, and 13.7 g or more per day). Furthermore, for 95 subjects who had been normotensive at 1998 among them, risk of development into HNBP or hypertension at 2000 were compared across the four subgroups. The findings showed that the HNBP prevalence adjusted for age, body mass index, smoking habits and sodium intake in 2000 was significantly (p=0.03) greater in 'TM or MM' type (57.9%) than in 'TT' type (24.9%) in subjects with 13.7 g or more of daily alcohol intake, whereas no difference in this parameter was found between the two genotypes in those with less than 13.7 g of daily alcohol intake (18.2% and 18.3%, respectively). The risk for development into HNBP at 2000 was also greatest in 'TM or MM' type with 13.7 g or more of daily alcohol intake among the four subgroups, although there were not significant differences between the four subgroups. The prevalence of hypertension or development risk for hypertension did not significantly differ between the four subgroups. Therefore, it can be seen that alcohol drinking might be specifically associated with the HNBP in M allele carriers of angiotensinogen gene T174M polymorphism.

Cytokine gene polymorphisms and atopic disease in two European cohorts. (ECRHS-Basel and SAPALDIA)

PubMed Central

Imboden, M; Nieters, A; Bircher, AJ; Brutsche, M; Becker, N; Wjst, M; Ackermann-Liebrich, U; Berger, W; Probst-Hensch, NM

2006-01-01

Background Atopy and allergic phenotypes are biologically characterized by an imbalanced T helper cell response skewed towards a type 2 (TH2) immune response associated with elevated serum immunoglobulin E (IgE) levels. Polymorphisms in cytokine genes might modulate regulation of the TH1/TH2 balance. We thus aimed at reproducing our previous findings from a European study population on the association of various cytokine polymorphisms with self-reported hay fever as well as increased total and specific IgE levels in two comparable study populations. Methods Two prospective Caucasian cohorts were used. In the Basel center of the European Community Respiratory Health Survey (ECRHS, n = 418) ten distinct cytokine polymorphisms of putative functional relevance were genotyped. In the Swiss cohort Study on Air Pollution And Lung Disease In Adults (SAPALDIA, n = 6003) two cytokine polymorphisms were genotyped. The associations of these polymorphisms with atopy were estimated by covariance and logistic regression analysis. Results We confirmed IL4, IL10, IL6 and IL18 as candidate genes for atopic health outcomes. In the large, well-characterized SAPALDIA cohort the IL6(-174G>C) and IL18(-137G>C) polymorphisms were associated with circulating total IgE concentrations in subjects with hay fever. The IL18(-137G>C) polymorphism was also associated with the prevalence of hay fever. Conclusion Comprehensive characterization of genetic variation in extended cytokine candidate gene regions is now needed. Large study networks must follow to investigate the association of risk patterns defined by genetic predisposing and environmental risk factors with specific atopic phenotypes. PMID:16759385

Sudden infant death syndrome (SIDS) and polymorphisms in Monoamine oxidase A gene (MAOA): a revisit.

PubMed

Groß, Maximilian; Bajanowski, Thomas; Vennemann, Mechtild; Poetsch, Micaela

2014-01-01

Literature describes multiple possible links between genetic variations in the neuroadrenergic system and the occurrence of sudden infant death syndrome. The X-chromosomal Monoamine oxidase A (MAOA) is one of the genes with regulatory activity in the noradrenergic and serotonergic neuronal systems and a polymorphism of the promoter which affects the activity of this gene has been proclaimed to contribute significantly to the prevalence of sudden infant death syndrome (SIDS) in three studies from 2009, 2012 and 2013. However, these studies described different significant correlations regarding gender or age of children. Since several studies, suggesting associations between genetic variations and SIDS, were disproved by follow-up analysis, this study was conducted to take a closer look at the MAOA gene and its polymorphisms. The functional MAOA promoter length polymorphism was investigated in 261 SIDS cases and 93 control subjects. Moreover, the allele distribution of 12 coding and non-coding single nucleotide polymorphisms (SNPs) of the MAOA gene was examined in 285 SIDS cases and 93 controls by a minisequencing technique. In contrast to prior studies with fewer individuals, no significant correlations between the occurrence of SIDS and the frequency of allele variants of the promoter polymorphism could be demonstrated, even including the results from the abovementioned previous studies. Regarding the SNPs, three statistically significant associations were observed which had not been described before. This study clearly disproves interactions between MAOA promoter polymorphisms and SIDS, even if variations in single nucleotide polymorphisms of MAOA should be subjected to further analysis to clarify their impact on SIDS.

Association of MBL2 Gene Polymorphism with Dental Caries in Saudi Children.

PubMed

Alyousef, Yousef M; Borgio, J Francis; AbdulAzeez, Sayed; Al-Masoud, Naif; Al-Ali, Ali A; Al-Shwaimi, Emad; Al-Ali, Amein K

2017-01-01

The high prevalence of dental caries in children worldwide is a major oral health problem which requires early intervention. Dental caries is mainly caused by the action of acids produced by bacteria in addition to many other factors. Recent genetic studies have reported that a number of genes are associated with the susceptibility to dental caries. The majority of these genes are associated with inflammation, increased susceptibility to infection, and dentine matrix formation. Using the TaqMan assay and direct DNA sequencing, the prevalence of 6 single-nucleotide polymorphisms (SNPs) in MMP9, MBL2, MMP2, and TIMP2 genes was determined in 102 children with caries and in 100 age-matched caries-free controls. Out of the 6 SNPs tested in the 4 selected genes, only rs11003125 in the MBL2 gene was shown to be associated with a high prevalence of caries in our cohort. In addition, haplotype analysis of the 6 SNPs tested revealed that certain haplotypes, namely GT of rs11003125G and rs7501477T and GT of rs7096206G and rs7501477T, were found to be associated with a high prevalence of dental caries in our cohort, while haplotype AG of rs17576A and rs7501477G was found to have a protective effect against dental caries. In conclusion, the data indicate that rs11003125 in the MBL2 gene was shown to be associated with a high prevalence of caries in our cohort, and 2 haplotypes are also involved in the increased susceptibility to dental caries. © 2016 S. Karger AG, Basel.

Association of HTRA1 polymorphism and bilaterality in advanced age-related macular degeneration.

PubMed

Chen, Haoyu; Yang, Zhenglin; Gibbs, Daniel; Yang, Xian; Hau, Vincent; Zhao, Peiquan; Ma, Xiang; Zeng, Jiexi; Luo, Ling; Pearson, Erik; Constantine, Ryan; Kaminoh, Yuuki; Harmon, Jennifer; Tong, Zongzhong; Stratton, Charity A; Cameron, D Joshua; Tang, Shibo; Zhang, Kang

2008-02-01

Single nucleotide polymorphism (SNP), rs11200638, in the promoter of HTRA1 has recently been shown to increase the risk for AMD. In order to investigate the association of this HTRA1 polymorphism and the bilaterality of AMD, we genotyped rs11200638 in control, unilateral, and bilateral advanced AMD patients. The A allele for SNP rs11200638 in HTRA1, was significantly more prevalent in bilateral wet AMD and GA patients than in unilateral groups (p=.02 and p=.03, respectively). The homozygote odds ratios of bilateral wet AMD and GA are significantly greater than those seen in unilateral groups (twofold and threefold increase, respectively). This finding is consistent with the role of HTRA1 in AMD pathogenesis and will help aid in the clinical management and prognosis of AMD patients.

Cassava chip (Manihot esculenta Crantz) as an energy source for ruminant feeding.

PubMed

Wanapat, Metha; Kang, Sungchhang

2015-12-01

Cassava ( Manihot esculenta Crantz) is widely grown in sub-tropical and tropical areas, producing roots as an energy source while the top biomass including leaves and immature stems can be sun-dried and used as cassava hay. Cassava roots can be processed as dried chip or pellet. It is rich in soluble carbohydrate (75 to 85%) but low in crude protein (2 to 3%). Its energy value is comparable to corn meal but has a relatively higher rate of rumen degradation. Higher levels of non-protein nitrogen especially urea (1 to 4%) can be successfully incorporated in concentrates containing cassava chip as an energy source. Cassava chip can also be processed with urea and other ingredients (tallow, sulfur, raw banana meal, cassava hay, and soybean meal) to make products such as cassarea, cassa-ban, and cassaya. Various studies have been conducted in ruminants using cassava chip to replace corn meal in the concentrate mixtures and have revealed satisfactory results in rumen fermentation efficiency and the subsequent production of meat and milk. In addition, it was advantageous when used in combination with rice bran in the concentrate supplement. Practical home-made-concentrate using cassava chip can be easily prepared for use on farms. A recent development has involved enriching protein in cassava chips, yielding yeast fermented cassava chip protein (YEFECAP) of up to 47.5% crude protein, which can be used to replace soybean meal. It is therefore, recommended to use cassava chip as an alternative source of energy to corn meal when the price is economical and it is locally available.

Quantitative trait loci controlling cyanogenic glucoside and dry matter content in cassava (Manihot esculenta Crantz) roots.

PubMed

Balyejusa Kizito, Elizabeth; Rönnberg-Wästljung, Ann-Christin; Egwang, Thomas; Gullberg, Urban; Fregene, Martin; Westerbergh, Anna

2007-09-01

Cassava (Manihot esculenta Crantz) is a starchy root crop grown in the tropics mainly by small-scale farmers even though agro-industrial processing is rapidly increasing. For this processing market improved varieties with high dry matter root content (DMC) is required. Potentially toxic cyanogenic glucosides are synthesized in the leaves and translocated to the roots. Selection for varieties with low cyanogenic glucoside potential (CNP) and high DMC is among the principal objectives in cassava breeding programs. However, these traits are highly influenced by the environmental conditions and the genetic control of these traits is not well understood. An S(1) population derived from a cross between two bred cassava varieties (MCOL 1684 and Rayong 1) that differ in CNP and DMC was used to study the heritability and genetic basis of these traits. A broad-sense heritability of 0.43 and 0.42 was found for CNP and DMC, respectively. The moderate heritabilities for DMC and CNP indicate that the phenotypic variation of these traits is explained by a genetic component. We found two quantitative trait loci (QTL) on two different linkage groups controlling CNP and six QTL on four different linkage groups controlling DMC. One QTL for CNP and one QTL for DMC mapped near each other, suggesting pleiotrophy and/or linkage of QTL. The two QTL for CNP showed additive effects while the six QTL for DMC showed additive effect, dominance or overdominance. This study is a first step towards developing molecular marker tools for efficient breeding of CNP and DMC in cassava.

Domestication Syndrome Is Investigated by Proteomic Analysis between Cultivated Cassava (Manihot esculenta Crantz) and Its Wild Relatives.

PubMed

An, Feifei; Chen, Ting; Stéphanie, Djabou Mouafi Astride; Li, Kaimian; Li, Qing X; Carvalho, Luiz J C B; Tomlins, Keith; Li, Jun; Gu, Bi; Chen, Songbi

2016-01-01

Cassava (Manihot esculenta Crantz) wild relatives remain a largely untapped potential for genetic improvement. However, the domestication syndrome phenomena from wild species to cultivated cassava remain poorly understood. The analysis of leaf anatomy and photosynthetic activity showed significantly different between cassava cultivars SC205, SC8 and wild relative M. esculenta ssp. Flabellifolia (W14). The dry matter, starch and amylose contents in the storage roots of cassava cultivars were significantly more than that in wild species. In order to further reveal the differences in photosynthesis and starch accumulation of cultivars and wild species, the globally differential proteins between cassava SC205, SC8 and W14 were analyzed using 2-DE in combination with MALDI-TOF tandem mass spectrometry. A total of 175 and 304 proteins in leaves and storage roots were identified, respectively. Of these, 122 and 127 common proteins in leaves and storage roots were detected in SC205, SC8 and W14, respectively. There were 11, 2 and 2 unique proteins in leaves, as well as 58, 9 and 12 unique proteins in storage roots for W14, SC205 and SC8, respectively, indicating proteomic changes in leaves and storage roots between cultivated cassava and its wild relatives. These proteins and their differential regulation across plants of contrasting leaf morphology, leaf anatomy pattern and photosynthetic related parameters and starch content could contribute to the footprinting of cassava domestication syndrome. We conclude that these global protein data would be of great value to detect the key gene groups related to cassava selection in the domestication syndrome phenomena.

Interleukin-21 gene polymorphism rs2221903 is associated with disease activity in patients with rheumatoid arthritis

PubMed Central

Malinowski, Damian; Paradowska-Gorycka, Agnieszka; Safranow, Krzysztof

2017-01-01

Introduction Interleukin-21 (IL-21) is a cytokine which plays a significant role in the pathogenesis and disease activity of rheumatoid arthritis (RA). Genetic polymorphisms in the IL-21 gene may alter the synthesis of IL-21. The aim of this study was to examine IL-21 and IL-21R polymorphisms in patients with RA. Material and methods We examined 422 patients with RA and 338 healthy controls. Single nucleotide polymorphisms (SNPs) within the IL-21 (rs6822844 G>T, rs6840978 C>T, rs2221903 T>C) and IL-21R (rs2285452 G>A) genes were genotyped using TaqMan genotyping assays. Results There were no statistically significant differences in the distribution of studied genotypes and alleles between RA patients and the control group. To examine whether IL-21 polymorphisms affect disease activity in RA patients, we compared the distribution of IL-21 genotypes between patients with DAS28 ≤ 2.5 (patients with remission of disease symptoms) and patients with DAS28 > 2.5 (patients with active RA). Among patients with DAS28 > 2.5, increased prevalence of rs2221903 CT and CC genotypes was observed (OR = 1.54; 95% CI: 1.04–2.28; p = 0.035). Conclusions The results of this study suggest that IL-21 and IL-21R gene polymorphisms are not risk loci for RA susceptibility, whereas the IL-21 rs2221903 polymorphism is associated with disease activity. PMID:28883856

PCR-based study of conserved and variable DNA sequences of Tritrichomonas foetus isolates from Saskatchewan, Canada.

PubMed Central

Riley, D E; Wagner, B; Polley, L; Krieger, J N

1995-01-01

The protozoan parasite Tritrichomonas foetus causes infertility and spontaneous abortion in cattle. In Saskatchewan, Canada, the culture prevalence of trichomonads was 65 of 1,048 (6%) among 1,048 bulls tested within a 1-year period ending in April 1994. Saskatchewan was previously thought to be free of the parasite. To confirm the culture results, possible T. foetus DNA presence was determined by the PCR. All of the 16 culture-positive isolates tested were PCR positive by a single-band test, but one PCR product was weak. DNA fingerprinting by both T17 PCR and randomly amplified polymorphic DNA PCR revealed genetic variation or polymorphism among the T. foetus isolates. T17 PCR also revealed conserved loci that distinguished these T. foetus isolates from Trichomonas vaginalis, from a variety of other protozoa, and from prokaryotes. TCO-1 PCR, a PCR test designed to sample DNA sequence homologous to the 5' flank of a highly conserved cell division control gene, detected genetic polymorphism at low stringency and a conserved, single locus at higher stringency. These findings suggested that T. foetus isolates exhibit both conserved genetic loci and polymorphic loci detectable by independent PCR methods. Both conserved and polymorphic genetic loci may prove useful for improved clinical diagnosis of T. foetus. The polymorphic loci detected by PCR suggested either a long history of infection or multiple lines of T. foetus infection in Saskatchewan. Polymorphic loci detected by PCR may provide data for epidemiologic studies of T. foetus. PMID:7615746

An African Ancestry-Specific Allele of CTLA4 Confers Protection against Rheumatoid Arthritis in African Americans

PubMed Central

Kelley, James M.; Hughes, Laura B.; Faggard, Jeffrey D.; Danila, Maria I.; Crawford, Monica H.; Edberg, Yuanqing; Padilla, Miguel A.; Tiwari, Hemant K.; Westfall, Andrew O.; Alarcón, Graciela S.; Conn, Doyt L.; Jonas, Beth L.; Callahan, Leigh F.; Smith, Edwin A.; Brasington, Richard D.; Allison, David B.; Kimberly, Robert P.; Moreland, Larry W.; Edberg, Jeffrey C.; Bridges, S. Louis

2009-01-01

Cytotoxic T-lymphocyte associated protein 4 (CTLA4) is a negative regulator of T-cell proliferation. Polymorphisms in CTLA4 have been inconsistently associated with susceptibility to rheumatoid arthritis (RA) in populations of European ancestry but have not been examined in African Americans. The prevalence of RA in most populations of European and Asian ancestry is ∼1.0%; RA is purportedly less common in black Africans, with little known about its prevalence in African Americans. We sought to determine if CTLA4 polymorphisms are associated with RA in African Americans. We performed a 2-stage analysis of 12 haplotype tagging single nucleotide polymorphisms (SNPs) across CTLA4 in a total of 505 African American RA patients and 712 African American controls using Illumina and TaqMan platforms. The minor allele (G) of the rs231778 SNP was 0.054 in RA patients, compared to 0.209 in controls (4.462×10−26, Fisher's exact). The presence of the G allele was associated with a substantially reduced odds ratio (OR) of having RA (AG+GG genotypes vs. AA genotype, OR 0.19, 95% CI: 0.13–0.26, p = 2.4×10−28, Fisher's exact), suggesting a protective effect. This SNP is polymorphic in the African population (minor allele frequency [MAF] 0.09 in the Yoruba population), but is very rare in other groups (MAF = 0.002 in 530 Caucasians genotyped for this study). Markers associated with RA in populations of European ancestry (rs3087243 [+60C/T] and rs231775 [+49A/G]) were not replicated in African Americans. We found no confounding of association for rs231778 after stratifying for the HLA-DRB1 shared epitope, presence of anti-cyclic citrullinated peptide antibody, or degree of admixture from the European population. An African ancestry-specific genetic variant of CTLA4 appears to be associated with protection from RA in African Americans. This finding may explain, in part, the relatively low prevalence of RA in black African populations. PMID:19300490

Interactions of Environmental Factors and APOA1-APOC3-APOA4-APOA5 Gene Cluster Gene Polymorphisms with Metabolic Syndrome.

PubMed

Wu, Yanhua; Yu, Yaqin; Zhao, Tiancheng; Wang, Shibin; Fu, Yingli; Qi, Yue; Yang, Guang; Yao, Wenwang; Su, Yingying; Ma, Yue; Shi, Jieping; Jiang, Jing; Kou, Changgui

2016-01-01

The present study investigated the prevalence and risk factors for Metabolic syndrome. We evaluated the association between single nucleotide polymorphisms (SNPs) in the apolipoprotein APOA1/C3/A4/A5 gene cluster and the MetS risk and analyzed the interactions of environmental factors and APOA1/C3/A4/A5 gene cluster polymorphisms with MetS. A study on the prevalence and risk factors for MetS was conducted using data from a large cross-sectional survey representative of the population of Jilin Province situated in northeastern China. A total of 16,831 participations were randomly chosen by multistage stratified cluster sampling of residents aged from 18 to 79 years in all nine administrative areas of the province. Environmental factors associated with MetS were examined using univariate and multivariate logistic regression analyses based on the weighted sample data. A sub-sample of 1813 survey subjects who met the criteria for MetS patients and 2037 controls from this case-control study were used to evaluate the association between SNPs and MetS risk. Genomic DNA was extracted from peripheral blood lymphocytes, and SNP genotyping was determined by MALDI-TOF-MS. The associations between SNPs and MetS were examined using a case-control study design. The interactions of environmental factors and APOA1/C3/A4/A5 gene cluster polymorphisms with MetS were assessed using multivariate logistic regression analysis. The overall adjusted prevalence of MetS was 32.86% in Jilin province. The prevalence of MetS in men was 36.64%, which was significantly higher than the prevalence in women (29.66%). MetS was more common in urban areas (33.86%) than in rural areas (31.80%). The prevalence of MetS significantly increased with age (OR = 8.621, 95%CI = 6.594-11.272). Mental labor (OR = 1.098, 95%CI = 1.008-1.195), current smoking (OR = 1.259, 95%CI = 1.108-1.429), excess salt intake (OR = 1.252, 95%CI = 1.149-1.363), and a fruit and dairy intake less than 2 servings a week were positively associated with MetS (P<0.05). A family history of diabetes (OR = 1.630, 95%CI = 1.484-1.791), cardiovascular disease or cerebral diseases (OR = 1.297, 95%CI = 1.211-1.389) was associated with MetS. APOA1 rs670, APOA5 rs662799 and rs651821 revealed significant differences in genotype distributions between the MetS patients and control subjects. The minor alleles of APOA1 rs670, APOA5 rs662799 and rs651821, and APOA5 rs2075291 were associated with MetS (P<0.0016). APOA1 rs5072 and APOC3 rs5128, APOA5 rs651821 and rs662799 were in strong linkage disequilibrium to each other with r2 greater than 0.8. Five haplotypes were associated with an increased risk of MetS (OR = 1.23, 1.58, 1.80, 1.90, and 1.98). When we investigated the interactions of environmental factors and APOA1/C3/A4/A5 gene cluster gene polymorphisms, we found that APOA5 rs662799 had interactions with tobacco use and alcohol consumption (PGE<0.05). There was a high prevalence of MetS in the northeast of China. Male gender, increasing age, mental labor, family history of diabetes, cardiovascular disease or cerebral diseases, current smoking, excess salt intake, fruit and dairy intake less than 2 servings a week, and drinking were associated with MetS. The APOA1/C3/A4/A5 gene cluster was associated with MetS in the Han Chinese. APOA5 rs662799 had interactions with the environmental factors associated with MetS.

Association between DNA methyltransferase gene polymorphism and Parkinson's disease.

PubMed

Pezzi, Julio Carlos; de Bem, Cintia Monique Boschmann Ens; da Rocha, Tatiane Jacobsen; Schumacher-Schuh, Artur F; Chaves, Marcia Lorena Fagundes; Rieder, Carlos Roberto; Hutz, Mara H; Fiegenbaum, Marilu; Camozzato, Ana Luiza

2017-02-03

Parkinson's disease (PD) is a common and complex neurodegenerative disorder, the second most prevalent, only behind Alzheimer's disease. Recent studies suggest that environmental factors may contribute for neurodegeneration through induction of epigenetic modifications, such as DNA methylation, that is carried out by enzymes, such as DNMT1 and DNMT3B. This present study targeted to investigate the association among DNMT1 and DNMT3B polymorphisms with PD. Five hundred and twenty-two participants (214 PD patients following UK Brain Bank criteria and 308 healthy individuals) were evaluated. DNA was obtained from whole blood and genotypes were detected by an allelic discrimination assay using TaqMan ® MGB probes on a real-time PCR system. The polymorphisms studied were rs2162560 and rs759920 (DNMT1) and rs2424913, rs998382 and rs2424932 (DNMT3B). Was found association between DNMT3B rs2424913 in T allele carriers with PD. The presence of the T allele was associated with PD (OR=1.80, 95% CI 1.16-2.81, p=0.009). No significant difference was observed for others DNMT3B SNPs. Also, no association between PD and the control group were observed for DNMT1 polymorphisms. This is the first study addressing an association between DNMT3B polymorphism and PD. The polymorphism may play a role in the pathogenesis of PD. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Polymorphisms rs12998 and rs5780218 in KiSS1 suppressor metastasis gene in Mexican patients with breast cancer.

PubMed

Quevedo, Edhit Guadalupe Cruz; Aguilar, Gabriela Monserrat Mimendi; Aguilar, Luis Anselmo Juárez; Rubio, Susan Andrea Gutierrez; Martínez, Silvia Esperanza Flores; Rodríguez, Ingrid Patricia Dávalos; Corona, José Sánchez; Morán, Martha Isabel Torres; Gómez, Roberto Carlos Rosales; Moguel, María Cristina Morán

2015-01-01

KiSS1 is a metastasis suppressor gene associated with inhibition of cellular chemotaxis and invasion attenuating the metastasis in melanoma and breast cancer cell lines. Along the KiSS-1 gene at least 294 SNPs have been described; however the association of these polymorphisms as genetic markers for metastasis in breast cancer studies has not been investigated. Here we describe two simple PCR-RFLPs protocols to identify the rs5780218 (9DelT) and the rs12998 (E20K) KiSS1 polymorphisms and the allelic, genotypic, and haplotypic frequencies in Mexican general population (GP) and patients with benign breast disease (BBD) or breast cancer (BC). The rs5780218 polymorphism was individually associated with breast cancer (P = 0.0332) and the rs12998 polymorphism shows statistically significant differences when GP versus case (BC and BBD) groups were compared (P < 0.0001). The H1 Haplotype (G/-) occurred more frequently in BC group (0.4256) whereas H2 haplotype (G/T) was the most prevalent in BBD group (0.4674). Our data indicated that the rs5780218 polymorphism individually confers susceptibility for development of breast cancer in Mexican population and a possible role as a genetic marker in breast cancer metastasis for H1 haplotype (Wt/variant) in KiSS1 gene must be analyzed in other populations.

Absence of correlation between IL-28B gene polymorphisms and the clinical presentation of chronic hepatitis B in an Amazon Brazilian population.

PubMed

Conde, Simone Regina Souza da Silva; Rocha, Luciana L; Ferreira, Vanessa M; Monteiro, Julius Caesar Mendes Soares; Filgueiras, Nathália Karla Fonseca; Lins, Pedro Alves de Almeida; dos Santos, Bruna Tereza Silva; Freitas, Felipe Bonfim; Graça, Ednelza da Silva; Demachki, Sâmia; de Araújo, Marialva Tereza Ferreira; Ishak, Ricardo; Vallinoto, Antonio C R

2014-01-01

The present study investigated the prevalence of the IL-28B polymorphisms rs12979860 and rs8099917 in chronic hepatitis B patients from a case study in Eastern Amazonia. In total, 65 chronically infected HBV patients and 97 healthy subjects who were anti-HBc and anti-HBs positive (control group) were evaluated between May 2011 and December 2012. The groups of patients were designated as inactive carriers, chronic hepatitis without cirrhosis, and chronic hepatitis with cirrhosis based on clinical, pathological, biochemical, hematological, and virological variables. The patients were genotyped using quantitative real-time PCR. The frequencies of the rs12979860 polymorphism were similar between the infected group (32.3% CC, 41.5% CT, and 26.2 TT) and the control population (35% CC, 47.4% CT, and 17.6% TT), and the frequencies of the rs8099917 polymorphism (7.7% GG, 35.4% GT, and 56.9% TT versus 7.2% GG, 35.1% GT, and 57.7% TT) were also similar in both groups. The associations between the rs12979860 and rs8099917 polymorphisms and the clinical manifestations were not statistically significant. In conclusion, these polymorphisms had a similar distribution between infected and control groups, indicating that they were not associated with susceptibility and the clinical evolution of hepatitis B in the examined population.

The Association of Polymorphisms in Leptin/Leptin Receptor Genes and Ghrelin/Ghrelin Receptor Genes With Overweight/Obesity and the Related Metabolic Disturbances: A Review.

PubMed

Ghalandari, Hamid; Hosseini-Esfahani, Firoozeh; Mirmiran, Parvin

2015-07-01

Leptin and ghrelin are two important appetite and energy balance-regulating peptides. Common polymorphisms in the genes coding these peptides and their related receptors are shown to be associated with body weight, different markers of obesity and metabolic abnormalities. This review article aims to investigate the association of common polymorphisms of these genes with overweight/obesity and the metabolic disturbances related to it. The keywords leptin, ghrelin, polymorphism, single-nucleotide polymorphism (SNP), obesity, overweight, Body Mass Index, metabolic syndrome, and type 2 diabetes mellitus (T2DM) (MeSH headings) were used to search in the following databases: Pubmed, Sciencedirect (Elsevier), and Google scholar. Overall, 24 case-control studies, relevant to our topic, met the criteria and were included in the review. The most prevalent leptin/leptin receptor genes (LEP/LEPR) and ghrelin/ghrelin receptor genes (GHRL/GHSR) single nucleotide polymorphisms studied were LEP G-2548A, LEPR Q223R, and Leu72Met, respectively. Nine studies of the 17 studies on LEP/LEPR, and three studies of the seven studies on GHRL/GHSR showed significant relationships. In general, our study suggests that the association between LEP/LEPR and GHRL/GHSR with overweight/obesity and the related metabolic disturbances is inconclusive. These results may be due to unidentified gene-environment interactions. More investigations are needed to further clarify this association.

Absence of association of FCGR2A gene polymorphism rs1801274 with Kawasaki disease in Greek patients.

PubMed

Chatzikyriakidou, Anthoula; Aidinidou, Louiza; Giannopoulos, Andreas; Papadopoulou-Legbelou, Kyriaki; Kalinderi, Kallirhoe; Fidani, Liana

2015-04-01

Kawasaki disease is an acute, febrile syndrome in infancy, characterised by vasculitis of medium-sized arteries, and affects predominantly young children. Family-based studies on Kawasaki disease supports the contribution of genetic factors in disorder manifestation. In a recent genome-wide association study, the polymorphism rs1801274 of FCGR2A [Fc fragment of immunoglobulin G, low-affinity IIa, receptor] gene has been implicated in disease pathogenesis. The aim of the present study was to explore the association of this variant, for the first time, in a group of Kawasaki-diseased patients of Greek origin. A total of 47 Kawasaki-diseased children and 50 control subjects were enrolled in the study. Polymerase chain reaction-restriction fragment length polymorphism assay was performed in rs1801274 genotyping. No association was observed between this polymorphism genotypes' or alleles' distribution between Kawasaki-diseased patients and controls. Furthermore, no association was revealed between this polymorphism and cardiovascular complications in Kawasaki-diseased patients. In the literature, the reported data over this polymorphism association with Kawasaki disease in Caucasian patients are contradictory. In addition, the disease shows low prevalence in the Caucasian populations. Therefore, the independent genetic association studies on rs1801274 with Kawasaki disease in various Caucasian groups increase the amount of genetic data, which could be used in a future meta-analysis, increasing the statistical power of the resultant conclusions.

Polymorphism of the p53 tumor suppressor gene is associated with susceptibility to uterine leiomyoma.

PubMed

Denschlag, Dominik; Bettendorf, Herta; Watermann, Dirk; Keck, Christoph; Tempfer, Clemens; Pietrowski, Detlef

2005-07-01

To evaluate the association between the presence of uterine leiomyoma and two single nuclear polymorphisms of the p53 tumor suppressor and the angiopoietin-2 (ANGPT2) genes. Prospective case control study. Academic research institution. One hundred thirty-two women with clinically and surgically diagnosed uterine leiomyomas and 280 controls. Peripheral venous puncture. Genotyping was performed by polymerase chain reaction-based amplification of the Arg and Pro variants at codon 72 of the p53 gene and by restriction fragment length polymorphism analysis of the G/G and G/A alleles in exon 4 of the ANGPT2 gene. Comparing women with uterine leiomyomas and controls, no statistically significant difference with respect to allele frequency and genotype distribution were ascertained for the ANGPT2 polymorphism (P=.2 and P=.5, respectively). However, for the p53 tumor suppressor gene polymorphism, statistically significant differences in terms of a higher Pro allele frequency and a higher prevalence of the Pro/Pro genotype among women with uterine leiomyoma (32.0% vs. 16.0%, respectively, and 21.3% vs. 4.7%, respectively) were ascertained (P=.001, OR 1.74; 95% CI 1.24-2.45, P=.001; OR 3.84, 95% CI 1.81-8.14; respectively). Carriage of the p53 polymorphism at codon 72 predicts the susceptibility to leiomyoma in a Caucasian population and may contribute to the pathogenesis of uterine leiomyoma.

ABCG8 polymorphisms and renal disease in type 2 diabetic patients.

PubMed

Nicolas, Anthony; Fatima, Sehrish; Lamri, Amel; Bellili-Muñoz, Naima; Halimi, Jean-Michel; Saulnier, Pierre-Jean; Hadjadj, Samy; Velho, Gilberto; Marre, Michel; Roussel, Ronan; Fumeron, Frédéric

2015-06-01

Sterols, bile acids and their receptors have been involved in diabetic nephropathy. The ATP-binding cassette transporters G5 and G8 (ABCG5 and ABCG8) play an important role in intestinal sterol absorption and bile acid secretion. The aim of our study was to assess the associations between two ABCG8 coding polymorphisms, T400K and D19H, and the incidence of renal events in type 2 diabetic subjects. Participants were the 3137 French type 2 diabetic subjects with micro- or macro-albuminuria from the genetic substudy of the DIABHYCAR trial. The mean duration of follow-up was 4years. Renal events were defined as a doubling of serum creatinine concentration or end-stage renal disease at follow-up. We then used a second population (DIAB2NEPHROGENE) of 2140 type 2 diabetic patients for the purpose of validation. In DIABHYCAR, the 400K allele was significantly associated with a higher risk of incident renal events in a multiple adjusted model (HR: 1.75 [95% CI 1.20-2.56], P=0.003). This association was still significant after further adjustments for baseline values of estimated glomerular filtration rate and urinary albumin excretion. In the validation population, the 400K allele was associated with the prevalence of end-stage renal disease (OR=2.01 [95% CI 1.15-3.54], P=0.015). No significant association was found between the D19H polymorphism and the risk of diabetic nephropathy. A polymorphism of the sterol transporter ABCG8 has been associated with the prevalence of end-stage renal disease and with the incidence of new renal events in type 2 diabetic patients. Copyright © 2015. Published by Elsevier Inc.

Inherited Thrombophilias Could Influence the Reproductive Outcome in Women with Systemic Lupus Erythematosus.

PubMed

Robeva, R; Tanev, D; Andonova, S; Nikolova, M; Tomova, A; Kumanov, Ph; Savov, A; Rashkov, R; Kolarov, Zl

2017-06-30

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease associated with different reproductive complications in the affected women. Inherited thrombophilias are genetic factors increasing the risk for thromboembolism and recurrent pregnancy loss, but their influence on other reproductive disturbances in SLE patients has not been completely clarified. Two hundred and twenty-three Caucasian women (112 with SLE and 111 controls) were included in the study. Complete reproductive history of all SLE patients was carefully obtained. Genotyping for the FV Leiden , FII G20210A , and MTHFR C677T polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. No significant differences in the prevalence of the FV Leiden , FII G20210A , and MTHFR C677T polymorphisms between patients and controls were established. Patients with FV Leiden had fewer pregnancies (0.57 ± 0.98 vs . 2.18 ± 1.58; p = 0.007) than the others, while no significant differences in the reproductive history of FII G20210A carriers and non-carriers were observed ( p >0.05). In the SLE group, 41.67% of women with the MTHFR C677T TT genotype had at least one miscarriage in comparison to only 14.00% of the other female patients ( p = 0.030). While the prevalence of the investigated thrombophilias was similar in patients with SLE and healthy women, a substantial influence of the inherited prothrombotic factors on the reproductive history of patients was revealed. The investigations of the FV Leiden and MTHFR C677T polymorphisms in SLE patients could help to identify women at highest risk for reproductive failure and thus, further studies in other ethnic groups would be of strong clinical importance.

Single Nucleotide Polymorphism in Gene Encoding Transcription Factor Prep1 Is Associated with HIV-1-Associated Dementia

PubMed Central

van Manen, Daniëlle; Bunnik, Evelien M.; van Sighem, Ard I.; Sieberer, Margit; Boeser-Nunnink, Brigitte; de Wolf, Frank; Schuitemaker, Hanneke; Portegies, Peter; Kootstra, Neeltje A.; van 't Wout, Angélique B.

2012-01-01

Background Infection with HIV-1 may result in severe cognitive and motor impairment, referred to as HIV-1-associated dementia (HAD). While its prevalence has dropped significantly in the era of combination antiretroviral therapy, milder neurocognitive disorders persist with a high prevalence. To identify additional therapeutic targets for treating HIV-associated neurocognitive disorders, several candidate gene polymorphisms have been evaluated, but few have been replicated across multiple studies. Methods We here tested 7 candidate gene polymorphisms for association with HAD in a case-control study consisting of 86 HAD cases and 246 non-HAD AIDS patients as controls. Since infected monocytes and macrophages are thought to play an important role in the infection of the brain, 5 recently identified single nucleotide polymorphisms (SNPs) affecting HIV-1 replication in macrophages in vitro were also tested. Results The CCR5 wt/Δ32 genotype was only associated with HAD in individuals who developed AIDS prior to 1991, in agreement with the observed fading effect of this genotype on viral load set point. A significant difference in genotype distribution among all cases and controls irrespective of year of AIDS diagnosis was found only for a SNP in candidate gene PREP1 (p = 1.2×10−5). Prep1 has recently been identified as a transcription factor preferentially binding the −2,518 G allele in the promoter of the gene encoding MCP-1, a protein with a well established role in the etiology of HAD. Conclusion These results support previous findings suggesting an important role for MCP-1 in the onset of HIV-1-associated neurocognitive disorders. PMID:22347417

P53 gene codon 72 polymorphism in patients with oral squamous cell carcinoma in the population of northern Iran.

PubMed

Sina, Mahmud; Pedram, Mehrdad; Ghojazadeh, Morteza; Kochaki, Ahmad; Aghbali, Amirala

2014-11-01

Squamous cell carcinoma is the most common cancer of the oral cavity, and several etiologic factors are involved in its developing. Single nucleotide polymorphism (SNP) of the P53 gene codon 72 (P53c72) changes the structure of the protein and affects its activity. The prevalence of P53c72 different genotypes, which seems to vary with race and geographic location, has shown a strong correlation with many types of human cancers. The aim of this study was to investigate the correlation between P53c72polymorphism and risk of oral squamous cell carcinoma (OSCC) in the heavily populated Gilan Province in northern Iran. This case-control study was done on 55 paraffin-embedded samples from OSCC patients and 100 samples of non-dysplastic oral cavity lesions. The P53c72 genotypes were determined using the ARMS-PCR method. SPSS-15 software was used for statistical analysis. There were no significant statistical differences found between the prevalence of different P53c72 genotypes in the OSCC group vs. the control. However, the Pro/Pro genotype in OSCC samples showed a strong correlation with age, as 70% of such patients were below 50 years old. Interestingly, a large portion (40%) of the patients with the Pro/Pro genotype had the tumor in the lip area. Although P53c72 polymorphism does not appear to be a predisposing factor for OSCC in the population of Northern Iran, the Pro/Pro genotype could be considered as a risk factor for OSCC in adults below 50 years old and the anatomical location of the tumor.

Role of treatment-modifying MTHFR677C>T and 1298A>C polymorphisms in metformin-treated Puerto Rican patients with type-2 diabetes mellitus and peripheral neuropathy.

PubMed

Jiménez-Ramírez, Francisco J; Castro, Liza M; Ortiz, Clarymar; Concepción, Jennifer; Renta, Jessicca Y; Morales-Borges, Raúl H; Miranda-Massari, Jorge R; Duconge, Jorge

2017-03-01

The study was conducted to investigate potential association between MTHFR genotypes and diabetic peripheral neuropathy (DPN) in Puerto Ricans with type-2 diabetes mellitus (T2DM) treated with metformin. The prevalence of major MTHFR polymorphisms in this cohort was also ascertained. DNAs from 89 metformin-treated patients with T2DM and DPN were genotyped using the PCR-based RFLP assay for MTHFR677C>T and 1298A>C polymorphisms. Frequency distributions of these variants in the study cohort were compared to those reported for three reference populations (HapMap project) and controls (400 newborn specimens). Chi-square (or Fischer's exact) tests and odds ratios (OR) were used to assess association with DPN susceptibility risk (patients vs. controls) and biochemical markers (wild types vs. carriers). Sixty-seven percent (67%) of participants carry at least one of these MTHFR polymorphisms. No deviations from Hardy-Weinberg equilibrium were detected. The genotype and allele frequencies showed statistically significant differences between participants and controls (p<0.0001 and p=0.03, respectively). Results suggest that 1298A>C but not 677C>T is associated with DPN susceptibility in this cohort (p=0.018). Different patterns of allelic dissimilarities are observed when comparing our cohort vs. the three parental ancestries. After sorting individuals by their carrier status, no significant associations were observed between these genetic variants (independently or combined) and any of the biochemical markers (HbA1c, folate, vitamin B12, homocysteine). Prevalence of major MTHFR variants in Puerto Rican patients with T2DM is first time ever reported. The study provides further evidence on the use of this genetic marker as an independent risk factor for DPN.

High circulating folate and vitamin B-12 concentrations in women during pregnancy are associated with increased prevalence of atopic dermatitis in their offspring.

PubMed

Kiefte-de Jong, Jessica C; Timmermans, Sarah; Jaddoe, Vincent W V; Hofman, Albert; Tiemeier, Henning; Steegers, Eric A; de Jongste, Johan C; Moll, Henriette A

2012-04-01

Recent studies suggest that in utero exposure of methyl donors influences programming of the fetal immune system in favor of development of allergic disease. The aim of this study was to assess whether the MTHFR C677T polymorphism, folic acid supplementation, and circulating folate and vitamin B-12 concentrations during pregnancy were associated with wheezing, shortness of breath, and atopic dermatitis in offspring. The study was a population-based birth cohort from fetal life until 48 mo (n = 8742). The use of folic acid supplementation during pregnancy was assessed by questionnaire. Plasma folate and serum vitamin B-12 concentrations and the MTHFR C677T polymorphism were available from blood collected in early pregnancy. Atopic dermatitis, wheezing, and shortness of breath in the offspring were assessed by parental-derived questionnaires at 12, 24, 36, and 48 mo. Maternal folate >16.2 nmol/L and vitamin B-12 >178 pmol/L were positively associated with the development of atopic dermatitis [adjusted OR: 1.18 (95% CI: 1.05-1.33) and adjusted OR: 1.30 (95% CI: 1.06-1.60) for the highest quartiles of folate and vitamin B-12 concentrations, respectively] but not with wheezing and shortness of breath. Maternal MTHFR C677T polymorphism and folic acid supplementation were not associated with wheezing, shortness of breath, and atopic dermatitis. No interactions were found by age, family history of atopy, folic acid supplementation, MTHFR C677T polymorphism, or maternal smoking (P-interaction > 0.10). High folate and vitamin B-12 levels during pregnancy are associated with increased prevalence of atopic dermatitis in the offspring. Potential risks of high folate and vitamin B-12 concentrations on allergic outcomes should be evaluated when discussing mandatory fortification programs.

Metabolic dysregulation in first-episode schizophrenia patients with respect to genetic variation in one-carbon metabolism.

PubMed

Misiak, Błażej; Łaczmański, Łukasz; Słoka, Natalia Kinga; Szmida, Elżbieta; Piotrowski, Patryk; Loska, Olga; Ślęzak, Ryszard; Kiejna, Andrzej; Frydecka, Dorota

2016-04-30

The aim of this study was to investigate the prevalence of metabolic disturbances in patients with first-episode schizophrenia (FES) and test the hypothesis that genetic variation in one-carbon metabolism may account for metabolic dysregulation in early psychosis. We measured fasting glucose, lipid profile parameters, homocysteine, folate and vitamin B12 in 135 patients with FES and 146 healthy controls (HCs). Polymorphisms in the following genes were determined: MTHFR (C677T and A1298C), MTHFD1 (G1958A), MTRR (A66G) and BHMT (G742A). Serum levels of folate and high-density lipoproteins (HDL) were significantly lower in patients with FES compared to HCs. In turn, serum levels of homocysteine and triglycerides were significantly higher in patients with FES than in HCs. Prevalence of hyperhomocysteinemia, low folate and HDL levels together with dyslipidemia was significantly higher in patients with FES compared to HCs. Higher homocysteine levels, lower vitamin B12 levels and the presence of metabolic syndrome were associated with higher severity of negative symptoms. None of studied polymorphisms was associated with schizophrenia risk. Several associations between studied polymorphisms and cardio-metabolic parameters were found. None of them remained significant after Bonferroni correction. Our results indicate that metabolic dysregulation in patients with FES is not associated with genetic variation in one-carbon metabolism. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Methylenetetrahydrofolate reductase C677T polymorphism and Factor V Leiden variant in Mexican women with preeclampsia/eclampsia.

PubMed

Dávalos, I P; Moran, M C; Martínez-Abundis, E; González-Ortiz, M; Flores-Martínez, S E; Machorro, V; Sandoval, L; Figuera, L E; Mena, J P; Oliva, J M; Tlacuilo-Parra, J A; Sánchez-Corona, J; Salazar-Páramo, M

2005-01-01

The etiology of preeclampsia is still a matter of controversy. An association between hyperhomocysteinemia and preeclamptic patients has been described. A common missense mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with increased plasma homocysteine concentrations. In addition, the polymorphism of gene encoding for Factor V Leiden G1691A is associated with a prothrombotic state in heterozygous subjects. Both mutations in these thrombophilic proteins appear to have different prevalence in the general population and in patients with preeclampsia/eclampsia (PE/E). We studied single nucleotide polymorphisms for MTHFR C677T and coagulation Factor V Leiden in 33 Mexican patients with PE/E as a genetic risk factor for these diseases, comparing with a normotensive pregnant control group. The genotype and allele frequencies of MTHFR C677T and Factor V Leiden mutations between Mexican women with PE/E and healthy controls were not different. We conclude that these polymorphisms do not contribute in the etiology of PE/E as it has been reported in other populations.

More Evidence for the Genetic Susceptibility of Mexican Population to Nonalcoholic Fatty Liver Disease through PNPLA3.

PubMed

Chinchilla-López, Paulina; Ramírez-Pérez, Oscar; Cruz-Ramón, Vania; Canizales-Quinteros, Samuel; Domínguez-López, Aarón; Ponciano-Rodríguez, Guadalupe; Sánchez-Muñoz, Fausto; Méndez-Sánchez, Nahum

2018-03-01

The gene for patatin-like phospholipase domain containing 3 (PNPLA3) is associated with nonalcoholic fatty liver disease (NAFLD) development. We previously found that Mexican indigenous population had the highest frequency reported of the PNPLA3 148M risk allele. Further, we observed a relationship between M148M genotype with elevated ALT levels in individuals with normal weight, overweight and obese. We sought to investigate whether PNPLA3 polymorphism is associated with NAFLD development in Mexicans. We enrolled 189 Mexican patients with NAFLD and 201 healthy controls. Anthropometric, metabolic, and biochemical variables were measured, and rs738409 (Ile148Met substitution) polymorphism was genotyped by sequencing. Logistic regression analysis, using a recessive model, suggested that PNPLA3 polymorphism in Mexican population is significantly associated (OR = 1.711, 95% CI: 1.014-2.886; P = 0.044) with NAFLD. The PNPLA3 gene is associated with NAFLD in Mexican population. More studies are required to explain the high prevalence of PNPLA3 polymorphism in Mexican-Americans, Mexican-Indians, and Mexican-Mestizos.

[Association of polymorphisms in toll-like receptor genes with atopic dermatitis in the Republic of Bashkortostan].

PubMed

Gimalova, G F; Karunas, A S; Fedorova, Iu Iu; Gumennaia, É R; Levasheva, S V; Khismatullina, Z R; Prans, E; Koks, S; Étkina, É I; Khusnutdinova, É K

2014-01-01

Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease developing as a result of the interaction between genetic predisposition and environmental factors. Considerable role in allergic diseases development is played by polymorphisms of genes of pattern-recognition receptors (PRR) which are capable of recognizing conservative standard molecular structures (patterns) unique for large pathogen groups. In this study polymorphic variants of PRR genes--Toll-like receptors (TLR1, TLR2, TLR4, TLR5, TLR6, TLR9, TLR10), NOD-like receptors (NOD1, NOD2), lipopolysaccharide receptor CD14 gene, and C11orf30 and LRRC32 genes, located in 11q13.5 region, have been investigated in AD patients and control subjects from the Republic of Bashkortostan. An association of TLR1 (rs5743571 and rs5743604), TLR6 (rs5743794) and TLR10 (rs11466617) with AD was found. Our results confirm an important role of the innate immune system in the pathogenesis of AD and the significance of polymorphisms within the Toll-like receptor 2 subfamily genes in AD development.

The mutagenicity of cassava (Manihot esculenta Crantz) preparations.

PubMed

De Meester, C; Rollmann, B; Mupenda, K; Mary, Y

1990-01-01

Different cassava products were found to contain mutagenic activities in the Ames test. This paper describes how the flavonol quercetin is released during the cooking of fresh cassava leaves, following a process very similar to culinary habits. The hydrolysis of the glucoside(s) and the release of free quercetin has been followed by the monitoring of mutagenic activities with a simultaneous isolation and purification by thin-layer chromatography. The fluorodensitometric method applied revealed that fresh leaves contained about 1300 mg quercetin per kg wet weight, of which 800 mg were released during a normal cooking process.

Cystic fibrosis transmembrane regulator haplotypes in households of patients with cystic fibrosis.

PubMed

Furgeri, Daniela Tenório; Marson, Fernando Augusto Lima; Correia, Cyntia Arivabeni Araújo; Ribeiro, José Dirceu; Bertuzzo, Carmen Sílvia

2018-01-30

Nearly 2000 mutations in the cystic fibrosis transmembrane regulator (CFTR) gene have been reported. The F508del mutation occurs in approximately 50-65% of patients with cystic fibrosis (CF). However, molecular diagnosis is not always possible. Therefore, silent polymorphisms can be used to label the mutant allele in households of patients with CF. To verify the haplotypes of four polymorphisms at the CFTR locus in households of patients with CF for pre-fertilization, pre-implantation, and prenatal indirect mutation diagnosis to provide better genetic counseling for families and patients with CF and to associate the genotypes/haplotypes with the F508del mutation screening. GATT polymorphism analysis was performed using direct polymerase chain reaction amplification, and the MP6-D9, TUB09 and TUB18 polymorphism analyses were performed using restriction fragment length polymorphism. Nine haplotypes were found in 37 CFTR alleles, and of those, 24 were linked with the F508del mutation and 13 with other CFTR mutations. The 6 (GATT), C (MP6-D9), G (TUB09), and C (TUB18) haplotypes showed the highest prevalence (48%) of the mutant CFTR allele and were linked to the F508del mutation (64%). In 43% of households analyzed, at least one informative polymorphism can be used for the indirect diagnostic test. CFTR polymorphisms are genetic markers that are useful for identifying the mutant CFTR alleles in households of patients with CF when it is not possible to establish the complete CFTR genotype. Moreover, the polymorphisms can be used for indirect CFTR mutation identification in cases of pre-fertilization, pre-implantation and prenatal analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

Polymorphism of DC-SIGN (CD209) promoter in association with clinical symptoms of dengue fever.

PubMed

Oliveira, Layanna Freitas de; Lima, Clayton Pereira Silva de; Azevedo, Raimunda do Socorro Silva; Mendonça, Dafne Silva Furtado de; Rodrigues, Sueli Guerreiro; Carvalho, Valéria Lima; Pinto, Eliana Vieira; Maia, Andreza Lopes; Maia, Maria Helena Thomaz; Vasconcelos, Janaina Mota; Silva, Andrea Luciana Soares da; Nunes, Márcio Roberto Teixeira; Sena, Leonardo; Vasconcelos, Pedro Fernando; Santos, Eduardo José Melo dos

2014-06-01

C-type lectin DC-SIGN receptor, encoded by CD209, plays a key role in the infection of dendritic cells by dengue virus (DENV). Because the -336A/G SNP (rs4804803) polymorphism in the promoter of CD209 modulates DC-SIGN expression, we investigated the putative association of this polymorphism with DENV infection and its pathogenesis. A control sample of 72 individuals, rigorously selected through a clinical investigation for absence of past dengue fever (DF) was compared to a sample of 168 patients (156 classical DF; 12 dengue hemorrhagic fever), all residents from Pará, Brazil. However, the prevalence of symptoms showed a trend higher in the AA genotype (Wilcoxon test; Z=2.02; p=0.04). Hence, our findings indicate that the G allele downregulates the spectrum of symptoms during the early acute phase of DENV infection, putatively decreasing the viremia, as suggested in the literature.

Recent developments in the study of opioid receptors.

PubMed

Cox, Brian M

2013-04-01

It is now about 40 years since Avram Goldstein proposed the use of the stereoselectivity of opioid receptors to identify these receptors in neural membranes. In 2012, the crystal structures of the four members of the opioid receptor family were reported, providing a structural basis for understanding of critical features affecting the actions of opiate drugs. This minireview summarizes these recent developments in our understanding of opiate receptors. Receptor function is also influenced by amino acid substitutions in the protein sequence. Among opioid receptor genes, one polymorphism is much more frequent in human populations than the many others that have been found, but the functional significance of this single nucleotide polymorphism (SNP) has been unclear. Recent studies have shed new light on how this SNP might influence opioid receptor function. In this minireview, the functional significance of the most prevalent genetic polymorphism among the opioid receptor genes is also considered.

Relationship among tobacco habits, human papilloma virus (HPV) infection, p53 polymorphism/mutation and the risk of oral squamous cell carcinoma.

PubMed

Chakrobarty, Bidyut; Roy, Jay Gopal; Majumdar, Sumit; Uppala, Divya

2014-05-01

The prevalence of oral squamous cell carcinoma (OSCC) has significantly increased over decades in several countries and human papilloma virus (HPV) has been indicated as one of the underlying causes. This suggests that HPV plays a role in the early stages of carcinogenesis but is not a requisite for the maintenance and progression of malignant state. p53 is a tumor suppressor gene that checks the cell and promotes apoptosis and cell repair that can be deactivated by mutations and a viral interaction leading to cancer and individuals with particular polymorphic variant of p53 is more susceptible to HPV-induced carcinogenesis. The present study has been carried out to detect and correlate p53 polymorphism/mutation, HPV DNA in the biopsy samples of oral cancer patients who had tobacco habits.

Cheating, trade-offs and the evolution of aggressiveness in a natural pathogen population

PubMed Central

Barrett, Luke; Bell, Thomas; Dwyer, Greg; Bergelson, Joy

2011-01-01

The evolutionary dynamics of pathogens are critically important for disease outcomes, prevalence and emergence. In this study we investigate ecological conditions that may promote the long-term maintenance of virulence polymorphisms in pathogen populations. Recent theory predicts that evolution towards increased virulence can be reversed if less aggressive social ‘cheats’ exploit more aggressive ‘cooperator’ pathogens. However, there is no evidence that social exploitation operates within natural pathogen populations. We show that for the bacterium Pseudomonas syringae, major polymorphisms for pathogenicity are maintained at unexpectedly high frequencies in populations infecting the host Arabidopsis thaliana. Experiments reveal that less aggressive strains substantially increase their growth potential in mixed infections and have a fitness advantage in non-host environments. These results suggest that niche differentiation can contribute to the maintenance of virulence polymorphisms, and that both within-host and between-host growth rates modulate cheating and cooperation in P. syringae populations. PMID:21951910

Serum protein polymorphisms in a Liberian population.

PubMed

Willcox, M; Beckman, G; Beckman, L

1986-01-01

Serum protein variations were studied in a Liberian population living in Buchanan town. Of the alpha 1-antitrypsin genes only M1 and M3 were polymorphic. The frequencies of the haptoglobin and Gc genes were in accordance with earlier known estimates in African populations. There was, however, a relatively low frequency of Hp 0 which may be related to the low malarial parasite prevalence in this group. The transferrin C2 gene was found in a significantly lower frequency among Liberians compared to European and Asiatic populations. A new transferrin variant was observed by isoelectric focusing. This variant could not be identified with conventional starch or polyacrylamide electrophoresis.

Phylogenetic reconstruction and polymorphism analysis of BK virus VP2 gene isolated from renal transplant recipients in China

PubMed Central

WANG, ZHANG-YANG; HONG, WEI-LONG; ZHU, ZHE-HUI; CHEN, YUN-HAO; YE, WEN-LE; CHU, GUANG-YU; LI, JIA-LIN; CHEN, BI-CHENG; XIA, PENG

2015-01-01

BK polyomavirus (BKV) is important pathogen for kidney transplant recipients, as it is frequently re-activated, leading to nephropathy. The aim of this study was to investigate the phylogenetic reconstruction and polymorphism of the VP2 gene in BKV isolated from Chinese kidney transplant recipients. Phylogenetic analysis was carried out in the VP2 region from 135 BKV-positive samples and 28 reference strains retrieved from GenBank. The unweighted pair-group method with arithmetic mean (UPGMA) grouped all strains into subtypes, but failed to subdivide strains into subgroups. Among the plasma and urine samples, all plasma (23/23) and 82 urine samples (82/95) were identified to contain subtype I; the other 10 urine samples contained subtype IV. A 86-bp fragment was identified as a highly conserved sequence. Following alignment with 36 published BKV sequences from China, 92 sites of polymorphism were identified, including 11 single nucleotide polymorphisms (SNPs) prevalent in Chinese individuals and 30 SNPs that were specific to the two predominant subtypes I and IV. The limitations of the VP2 gene segment in subgrouping were confirmed by phylogenetic analysis. The conserved sequence and polymorphism identified in this study may be helpful in the detection and genotyping of BKV. PMID:26640547

Smoking has no impact on survival and it is not associated with ACE gene I/D polymorphism in hemodialysis patients.

PubMed

Kiss, István; Kiss, Zoltán; Kerkovits, Lóránt; Paksy, András; Ambrus, Csaba

2017-01-01

The relationship between smoking and mortality in patients on hemodialysis is controversial. Earlier studies showed that the insertion/deletion (I/D) polymorphism of the ACE gene might have an effect on mortality. The aim of this study was to test the impact of smoking on survival and whether this association was influenced by ACE gene I/D polymorphism in patients on maintenance hemodialysis. In this prospective, multicenter cohort study we analyzed 709 prevalent patients on maintenance hemodialysis. Patients were allocated into groups based on their smoking habit. Outcome data were collected during the 144-month follow-up period. Outcomes of current smokers and lifelong non-smokers were compared. In order to control for interactions between predictor variables, we also identified 160 matched pairs for further sub-analysis. The vast majority of patients (67%) were non-smokers, followed by current smokers (22.2%) and ex-smokers (9.8%). Smoking had no impact on survival in the matched pair analysis ( p = 0.99). After adjustment for ACE I/D polymorphism and other co-variates, smoking had no effect on survival. Our data suggest that smoking has no impact on survival; neither is it associated with ACE gene I/D polymorphism in hemodialysis patients.

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.

Paraoxonase 1 (PON1) gene-108C>T and p.Q192R polymorphisms and arylesterase activity of the enzyme in patients with dementia.

PubMed

Bednarska-Makaruk, Małgorzata Ewa; Krzywkowski, Tomasz; Graban, Alla; Lipczyńska-Łojkowska, Wanda; Bochyńska, Anna; Rodo, Maria; Wehr, Hanna; Ryglewicz, Danuta Krystyna

2013-01-01

Paraoxonase 1 (PON1) activity was determined using phenylacetate as substrate (arylesterase activity) in 304 individuals with dementia--136 recognised as probable Alzheimer's disease (AD), 64 as dementia of vascular origin (VaD) and 104 as mixed dementia (MD) and in 129 persons without symptoms of dementia and in a good general health. -108C>T polymorphism in the PON1 gene promoter and p.Q192R polymorphism in the coding region were identified. PON1 activity was significantly lower in demented patients as compared with controls particularly in dementia of a neurodegenerative character (AD and MD). The prevalence of PON1-108T allele carriers was significantly higher in the AD group than in controls. The frequencies of the p.Q192R genotypes did not differ significantly between the investigated groups. An association of the rare T-R haplotype with dementia, particularly with dementia of the neurodegenerative type, was found. Multivariate regression analysis showed a significant association of PON1 activity with PON1 -108C>T and p.Q192R polymorphisms. The influence not only of promoter -108C>T, but also of p.Q192R polymorphism on PON1 arylesterase activity was observed. One has to admit that this kind of polymorphism does not preclude interference with the enzyme activity. It could be concluded that the PON1 gene promoter polymorphism plays an additional role in Alzheimer's disease development. It seems however that PON1 activity has a dominating influence on the dementia risk.

HLA-DQBl*0402 alleles polymorphisms detected in Javanese HIV patients with positive anti-Toxoplasma gondii IgM

NASA Astrophysics Data System (ADS)

Sari, Yulia; Haryati, Sri; Prasetyo, Afiono Agung; Hartono, Adnan, Zainal Arifin

2017-02-01

The human leukocyte antigen (HLA)-DQB1 gene polymorphisms may associated with the infection risk of Toxoplasma gondii in HIV patients. The HLA-DQB1*0402 in HIV-1-positive patients could be considered risk factors for developing neurological opportunistic infections, mainly Toxoplasma encephalitis. However, the HLA-DQB1*0402 gene polymorphisms status in the Javanese HIV patients is unknown. This study evaluated the prevalence of HLA-DQB*0402 alleles polymorphisms in Javanese HIV patients with positive anti-Toxoplasma gondii IgM status. Since 2009 our research group performing a molecular epidemiology of blood borne viruses in Central Java Indonesia, by collecting the epidemiological and clinical data from the high risk communities. All blood samples were screened for blood borne pathogens by serological and molecular assays including for HIV and Toxoplasma gondii. The genomic DNA was isolated from the whole blood samples. Genetic polymorphisms of HLA-DQB1*0402 alleles were detected with polymerase chain reaction-sequence-specific primers (PCR-SSPs) technique. The genotypes were defined according to generated fragment patterns in the agarose gel electrophoresis analysis of PCR products. All of the samples were tested at least in duplicate. HLA-DQB1*0402 alleles were detected in 20.8% (16/77) patients and not detected in all HIV positive samples with negative anti-Toxoplasma gondii IgM status (n= 200). The HLA-DQB1*0402 alleles polymorphisms were detected in Javanese HIV patients with positive anti-Toxoplasma gondii IgM. The polymorphisms found may have association with the infection risk of Toxoplasma gondii in HIV patients.

Single nucleotide polymorphisms and microsatellites in the canine glutathione S-transferase pi 1 (GSTP1) gene promoter.

PubMed

Sacco, James; Mann, Sarah; Toral, Keller

2017-01-01

Genetic polymorphisms within the glutathione S-transferase P1 ( GSTP1 ) gene affect the elimination of toxic xenobiotics by the GSTP1 enzyme. In dogs, exposure to environmental chemicals that may be GSTP1 substrates is associated with cancer. The objectives of this study were to investigate the genetic variability in the GSTP1 promoter in a diverse population of 278 purebred dogs, compare the incidence of any variants found between breeds, and predict their effects on gene expression. To provide information on ancestral alleles, a number of wolves, coyotes, and foxes were also sequenced. Fifteen single nucleotide polymorphisms (SNPs) and two microsatellites were discovered. Three of these loci were only polymorphic in dogs while three other SNPs were unique to wolves and coyotes. The major allele at c.-46 is T in dogs but is C in the wild canids. The c.-185 delT variant was unique to dogs. The microsatellite located in the 5' untranslated region (5'UTR) was a highly polymorphic GCC tandem repeat, consisting of simple and compound alleles that varied in size from 10 to 22-repeat units. The most common alleles consisted of 11, 16, and 17-repeats. The 11-repeat allele was found in 10% of dogs but not in the other canids. Unequal recombination and replication slippage between similar and distinct alleles may be the mechanism for the multiple microsatellites observed. Twenty-eight haplotypes were constructed in the dog, and an additional 8 were observed in wolves and coyotes. While the most common haplotype acrossbreeds was the wild-type *1A(17), other prevalent haplotypes included *3A(11) in Greyhounds, *6A(16) in Labrador Retrievers, *9A(16) in Golden Retrievers, and *8A(19) in Standard Poodles. Boxers and Siberian Huskies exhibited minimal haplotypic diversity. Compared to the simple 16*1 allele, the compound 16*2 allele (found in 12% of dogs) may interfere with transcription factor binding and/or the stability of the GSTP1 transcript. Dogs and other canids exhibit extensive variation in the GSTP1 promoter. Genetic polymorphisms within distinct haplotypes prevalent in certain breeds can affect GSTP1 expression and carcinogen detoxification, and thus may be useful as genetic markers for cancer in dogs.

Antioxidant and Antiradical Activities of Manihot esculenta Crantz (Euphorbiaceae) Leaves and Other Selected Tropical Green Vegetables Investigated on Lipoperoxidation and Phorbol-12-myristate-13-acetate (PMA) Activated Monocytes

PubMed Central

Tsumbu, Cesar N.; Deby-Dupont, Ginette; Tits, Monique; Angenot, Luc; Franck, Thierry; Serteyn, Didier; Mouithys-Mickalad, Ange

2011-01-01

Abelmoschus esculentus (Malvaceae), Hibiscus acetosella (Malvaceae), Manihot esculenta Crantz (Euphorbiaceae) and Pteridium aquilinum (Dennstaedtiaceae) leaves are currently consumed as vegetables by migrants from sub-Saharan Africa living in Western Europe and by the people in the origin countries, where these plants are also used in the folk medicine. Manihot leaves are also eaten in Latin America and some Asian countries. This work investigated the capacity of aqueous extracts prepared from those vegetables to inhibit the peroxidation of a linoleic acid emulsion. Short chain, volatile C-compounds as markers of advanced lipid peroxidation were measured by gas chromatography by following the ethylene production. The generation of lipid hydroperoxides, was monitored by spectroscopy using N-N′-dimethyl-p-phenylene-diamine (DMPD). The formation of intermediate peroxyl, and other free radicals, at the initiation of the lipid peroxidation was investigated by electron spin resonance, using α-(4-pyridyl-1-oxide)-N-tert-butylnitrone as spin trap agent. The ability of the extracts to decrease the cellular production of reactive oxygen species (ROS) in “inflammation like” conditions was studied by fluorescence technique using 2′,7′-dichlorofluorescine-diacetate as fluorogenic probe, in a cell model of human monocytes (HL-60 cells) activated with phorbol ester. Overall the extracts displayed efficient concentration-dependent inhibitory effects. Their total polyphenol and flavonoid content was determined by classic colorimetric methods. An HPLC-UV/DAD analysis has clearly identified the presence of some polyphenolic compounds, which explains at least partially the inhibitions observed in our models. The role of these plants in the folk medicine by sub-Saharan peoples as well as in the prevention of oxidative stress and ROS related diseases requires further consideration. PMID:22254126

Quantitative trait loci and candidate genes associated with starch pasting viscosity characteristics in cassava (Manihot esculenta Crantz).

PubMed

Thanyasiriwat, T; Sraphet, S; Whankaew, S; Boonseng, O; Bao, J; Lightfoot, D A; Tangphatsornruang, S; Triwitayakorn, K

2014-01-01

Starch pasting viscosity is an important quality trait in cassava (Manihot esculenta Crantz) cultivars. The aim here was to identify loci and candidate genes associated with the starch pasting viscosity. Quantitative trait loci (QTL) mapping for seven pasting viscosity parameters was carried out using 100 lines of an F1 mapping population from a cross between two cassava cultivars Huay Bong 60 and Hanatee. Starch samples were obtained from roots of cassava grown in 2008 and 2009 at Rayong, and in 2009 at Lop Buri province, Thailand. The traits showed continuous distribution among the F1 progeny with transgressive variation. Fifteen QTL were identified from mean trait data, with Logarithm of Odds (LOD) values from 2.77-13.01 and phenotype variations explained (PVE) from10.0-48.4%. In addition, 48 QTL were identified in separate environments. The LOD values ranged from 2.55-8.68 and explained 6.6-43.7% of phenotype variation. The loci were located on 19 linkage groups. The most important QTL for pasting temperature (PT) (qPT.1LG1) from mean trait values showed largest effect with highest LOD value (13.01) and PVE (48.4%). The QTL co-localised with PT and pasting time (PTi) loci that were identified in separate environments. Candidate genes were identified within the QTL peak regions. However, the major genes of interest, encoding the family of glycosyl or glucosyl transferases and hydrolases, were located at the periphery of QTL peaks. The loci identified could be effectively applied in breeding programmes to improve cassava starch quality. Alleles of candidate genes should be further studied in order to better understand their effects on starch quality traits. © 2013 German Botanical Society and The Royal Botanical Society of the Netherlands.

RNAi inhibition of feruloyl CoA 6'-hydroxylase reduces scopoletin biosynthesis and post-harvest physiological deterioration in cassava (Manihot esculenta Crantz) storage roots.

PubMed

Liu, Shi; Zainuddin, Ima M; Vanderschuren, Herve; Doughty, James; Beeching, John R

2017-05-01

Cassava (Manihot esculenta Crantz) is a major world crop, whose storage roots provide food for over 800 million throughout the humid tropics. Despite many advantages as a crop, the development of cassava is seriously constrained by the rapid post-harvest physiological deterioration (PPD) of its roots that occurs within 24-72 h of harvest, rendering the roots unpalatable and unmarketable. PPD limits cassava's marketing possibilities in countries that are undergoing increased development and urbanisation due to growing distances between farms and consumers. The inevitable wounding of the roots caused by harvesting triggers an oxidative burst that spreads throughout the cassava root, together with the accumulation of secondary metabolites including phenolic compounds, of which the coumarin scopoletin (7-hydroxy-6-methoxy-2H-1-benzopyran-2-one) is the most abundant. Scopoletin oxidation yields a blue-black colour, which suggests its involvement in the discoloration observed during PPD. Feruloyl CoA 6'-hydroxylase is a controlling enzyme in the biosynthesis of scopoletin. The cassava genome contains a seven membered family of feruloyl CoA 6'-hydroxylase genes, four of which are expressed in the storage root and, of these, three were capable of functionally complementing Arabidopsis T-DNA insertion mutants in this gene. A RNA interference construct, designed to a highly conserved region of these genes, was used to transform cassava, where it significantly reduced feruloyl CoA 6'-hydroxylase gene expression, scopoletin accumulation and PPD symptom development. Collectively, our results provide evidence that scopoletin plays a major functional role in the development of PPD symptoms, rather than merely paralleling symptom development in the cassava storage root.

Increased expression of native cytosolic Cu/Zn superoxide dismutase and ascorbate peroxidase improves tolerance to oxidative and chilling stresses in cassava (Manihot esculenta Crantz)

PubMed Central

2014-01-01

Background Cassava (Manihot esculenta Crantz) is a tropical root crop, and is therefore, extremely sensitive to low temperature; its antioxidative response is pivotal for its survival under stress. Timely turnover of reactive oxygen species (ROS) in plant cells generated by chilling-induced oxidative damages, and scavenging can be achieved by non-enzymatic and enzymatic reactions in order to maintain ROS homeostasis. Results Transgenic cassava plants that co-express cytosolic superoxide dismutase (SOD), MeCu/ZnSOD, and ascorbate peroxidase (APX), MeAPX2, were produced and tested for tolerance against oxidative and chilling stresses. The up-regulation of MeCu/ZnSOD and MeAPX2 expression was confirmed by the quantitative reverse transcriptase-polymerase chain reaction, and enzymatic activity analyses in the leaves of transgenic cassava plant lines with a single-transgene integration site. Upon exposure to ROS-generating agents, 100 μM ROS-generating reagent methyl viologen and 0.5 M H2O2, higher levels of enzymatic activities of SOD and APX were detected in transgenic plants than the wild type. Consequently, the oxidative stress parameters, such as lipid peroxidation, chlorophyll degradation and H2O2 synthesis, were lower in the transgenic lines than the wild type. Tolerance to chilling stress at 4°C for 2 d was greater in transgenic cassava, as observed by the higher levels of SOD, catalase, and ascorbate-glutathione cycle enzymes (e.g., APX, monodehydroascorbate reductase, dehydroascorbate reducatase and glutathione reductase) and lower levels of malondialdehyde content. Conclusions These results suggest that the expression of native cytosolic SOD and APX simultaneously activated the antioxidative defense mechanisms via cyclic ROS scavenging, thereby improving its tolerance to cold stress. PMID:25091029

Ground penetrating radar: a case study for estimating root bulking rate in cassava (Manihot esculenta Crantz).

PubMed

Delgado, Alfredo; Hays, Dirk B; Bruton, Richard K; Ceballos, Hernán; Novo, Alexandre; Boi, Enrico; Selvaraj, Michael Gomez

2017-01-01

Understanding root traits is a necessary research front for selection of favorable genotypes or cultivation practices. Root and tuber crops having most of their economic potential stored below ground are favorable candidates for such studies. The ability to image and quantify subsurface root structure would allow breeders to classify root traits for rapid selection and allow agronomist the ability to derive effective cultivation practices. In spite of the huge role of Cassava ( Manihot esculenta Crantz), for food security and industrial uses, little progress has been made in understanding the onset and rate of the root-bulking process and the factors that influence it. The objective of this research was to determine the capability of ground penetrating radar (GPR) to predict root-bulking rates through the detection of total root biomass during its growth cycle. Our research provides the first application of GPR for detecting below ground biomass in cassava. Through an empirical study, linear regressions were derived to model cassava bulking rates. The linear equations derived suggest that GPR is a suitable measure of root biomass ( r  = .79). The regression analysis developed accounts for 63% of the variability in cassava biomass below ground. When modeling is performed at the variety level, it is evident that the variety models for SM 1219-9 and TMS 60444 outperform the HMC-1 variety model (r 2  = .77, .63 and .51 respectively). Using current modeling methods, it is possible to predict below ground biomass and estimate root bulking rates for selection of early root bulking in cassava. Results of this approach suggested that the general model was over predicting at early growth stages but became more precise in later root development.

Domestication Syndrome Is Investigated by Proteomic Analysis between Cultivated Cassava (Manihot esculenta Crantz) and Its Wild Relatives

PubMed Central

An, Feifei; Chen, Ting; Stéphanie, Djabou Mouafi Astride; Li, Kaimian; Li, Qing X.; Carvalho, Luiz J. C. B.; Tomlins, Keith; Li, Jun; Gu, Bi; Chen, Songbi

2016-01-01

Cassava (Manihot esculenta Crantz) wild relatives remain a largely untapped potential for genetic improvement. However, the domestication syndrome phenomena from wild species to cultivated cassava remain poorly understood. The analysis of leaf anatomy and photosynthetic activity showed significantly different between cassava cultivars SC205, SC8 and wild relative M. esculenta ssp. Flabellifolia (W14). The dry matter, starch and amylose contents in the storage roots of cassava cultivars were significantly more than that in wild species. In order to further reveal the differences in photosynthesis and starch accumulation of cultivars and wild species, the globally differential proteins between cassava SC205, SC8 and W14 were analyzed using 2-DE in combination with MALDI-TOF tandem mass spectrometry. A total of 175 and 304 proteins in leaves and storage roots were identified, respectively. Of these, 122 and 127 common proteins in leaves and storage roots were detected in SC205, SC8 and W14, respectively. There were 11, 2 and 2 unique proteins in leaves, as well as 58, 9 and 12 unique proteins in storage roots for W14, SC205 and SC8, respectively, indicating proteomic changes in leaves and storage roots between cultivated cassava and its wild relatives. These proteins and their differential regulation across plants of contrasting leaf morphology, leaf anatomy pattern and photosynthetic related parameters and starch content could contribute to the footprinting of cassava domestication syndrome. We conclude that these global protein data would be of great value to detect the key gene groups related to cassava selection in the domestication syndrome phenomena. PMID:27023871

Toxic effects of prolonged administration of leaves of cassava (Manihot esculenta Crantz) to goats.

PubMed

Soto-Blanco, Benito; Górniak, Silvana Lima

2010-07-01

Cassava (Manihot esculenta Crantz) is a major source of dietary energy for humans and domestic animals in many tropical countries. However, consumption of cassava is limited by its characteristic content of cyanogenic glycosides. The present work aimed to evaluate the toxic effects of ingestion of cassava leaves by goats for 30 consecutive days, and to compare the results with the toxic effects of cyanide in goats, which have been described previously. Eight Alpine cross-bred female goats were divided into two equal groups, and were treated with ground frozen cassava leaves at a target dose of 6.0mg hydrogen cyanide (HCN)/kg/day (treated animals), or with ground hay and water only (control group) by gavage for 30 consecutive days. Blood samples were collected on days 0, 7, 15, 21, and 30 for biochemical panel and cyanide determination. At the end of the experiment, fragments of pancreas, thyroid gland, liver, kidney, lungs, heart, spleen, and the whole central nervous system were collected for histopathological examination. Clinical signs were observed in all goats treated with cassava on the first day of the experiment. From the second day the dose of cassava leaves was reduced to 4.5mgHCN/kg/day. No changes were found in the blood chemical panel. A mild increase in the number of resorption vacuoles in the thyroid follicular colloid, slight vacuolation of periportal hepatocytes, and spongiosis of the mesencephalon were found in goats treated with cassava. The pattern of lesions seen in the present goats was similar to what has been described previously in cyanide-dosed goats. Thus, the toxic effects of the ingestion of cassava leaves by goats can be attributed to the action of cyanide released from cyanogenic glycosides, and none of the effects was promoted by these glycosides directly.

Increased expression of native cytosolic Cu/Zn superoxide dismutase and ascorbate peroxidase improves tolerance to oxidative and chilling stresses in cassava (Manihot esculenta Crantz).

PubMed

Xu, Jia; Yang, Jun; Duan, Xiaoguang; Jiang, Yueming; Zhang, Peng

2014-08-05

Cassava (Manihot esculenta Crantz) is a tropical root crop, and is therefore, extremely sensitive to low temperature; its antioxidative response is pivotal for its survival under stress. Timely turnover of reactive oxygen species (ROS) in plant cells generated by chilling-induced oxidative damages, and scavenging can be achieved by non-enzymatic and enzymatic reactions in order to maintain ROS homeostasis. Transgenic cassava plants that co-express cytosolic superoxide dismutase (SOD), MeCu/ZnSOD, and ascorbate peroxidase (APX), MeAPX2, were produced and tested for tolerance against oxidative and chilling stresses. The up-regulation of MeCu/ZnSOD and MeAPX2 expression was confirmed by the quantitative reverse transcriptase-polymerase chain reaction, and enzymatic activity analyses in the leaves of transgenic cassava plant lines with a single-transgene integration site. Upon exposure to ROS-generating agents, 100 μM ROS-generating reagent methyl viologen and 0.5 M H₂O₂, higher levels of enzymatic activities of SOD and APX were detected in transgenic plants than the wild type. Consequently, the oxidative stress parameters, such as lipid peroxidation, chlorophyll degradation and H₂O₂ synthesis, were lower in the transgenic lines than the wild type. Tolerance to chilling stress at 4°C for 2 d was greater in transgenic cassava, as observed by the higher levels of SOD, catalase, and ascorbate-glutathione cycle enzymes (e.g., APX, monodehydroascorbate reductase, dehydroascorbate reducatase and glutathione reductase) and lower levels of malondialdehyde content. These results suggest that the expression of native cytosolic SOD and APX simultaneously activated the antioxidative defense mechanisms via cyclic ROS scavenging, thereby improving its tolerance to cold stress.

Unveiling the Micronome of Cassava (Manihot esculenta Crantz)

PubMed Central

2016-01-01

MicroRNAs (miRNAs) are an important class of endogenous non-coding single-stranded small RNAs (21–24 nt in length), which serve as post-transcriptional negative regulators of gene expression in plants. Despite the economic importance of Manihot esculenta Crantz (cassava) only 153 putative cassava miRNAs (from multiple germplasm) are available to date in miRBase (Version 21), and identification of a number of miRNAs from the cassava EST database have been limited to comparisons with Arabidopsis. In this study, mature sequences of all known plant miRNAs were used as a query for homologous searches against cassava EST and GSS databases, and additional identification of novel and conserved miRNAs were gleaned from next generation sequencing (NGS) of two cassava landraces (T200 from southern Africa and TME3 from West Africa) at three different stages post explant transplantation and acclimatization. EST and GSS derived data revealed 259 and 32 miRNAs in cassava, and one of the miRNA families (miR2118) from previous studies has not been reported in cassava. NGS data collectively displayed expression of 289 conserved miRNAs in leaf tissue, of which 230 had not been reported previously. Of the 289 conserved miRNAs identified in T200 and TME3, 208 were isomiRs. Thirty-nine novel cassava-specific miRNAs of low abundance, belonging to 29 families, were identified. Thirty-eight (98.6%) of the putative new miRNAs identified by NGS have not been previously reported in cassava. Several miRNA targets were identified in T200 and TME3, highlighting differential temporal miRNA expression between the two cassava landraces. This study contributes to the expanding knowledge base of the micronome of this important crop. PMID:26799216

A Polymorphism in the Retinol Binding Protein 4 Gene is Not Associated with Gestational Diabetes Mellitus in Several Different Ethnic Groups

PubMed Central

Urschitz, Johann; Sultan, Omar; Ward, Kenneth

2011-01-01

Objective Various Asian and Pacifific Islander groups have higher prevalence rates of type 2 diabetes and gestational diabetes. This increased incidence is likely to include genetic factors. Single nucleotide polymorphisms in the retinol binding protein 4 gene have been linked to the occurrence of type 2 diabetes. Hypothesizing a link between retinol binding protein 4 and gestational diabetes, we performed a candidate gene study to look for an association between an important retinol binding protein gene polymorphism (rs3758539) and gestational diabetes. Study Design Blood was collected from Caucasian, Asian, and Pacific Islander women diagnosed with gestational diabetes and from ethnically matched non-diabetic controls. DNA was extracted and real time PCR technology (TaqMan, Applied Biosystems) used to screen for the rs3758539 single nucleotide polymorphism located 5′ of exon 1 of the retinol binding protein 4 gene. Results Genotype and allele frequencies in the controls and gestational diabetes cases were tested using chi-square contingency tests. Genotype frequencies were in Hardy-Weinberg equilibrium. There was no association between the rs3758539 retinol binding protein 4 single nucleotide polymorphism and gestational diabetes in the Caucasian, Filipino, or Pacific Islander groups. Conclusion Interestingly, the rs3758539 retinol binding protein 4 single nucleotide polymorphism was not found to be associated with gestational diabetes. The absence of association suggests that gestational and type 2 diabetes may have more divergent molecular pathophysiology than previously suspected. PMID:21886308

Apolipoprotein A-V: a potential modulator of plasma triglyceride levels in Turks.

PubMed

Hodoglugil, Ugur; Tanyolaç, Sinan; Williamson, David W; Huang, Yadong; Mahley, Robert W

2006-01-01

The apolipoprotein A-V gene (APOA5) plays an important role in determining plasma triglyceride levels. We studied the effects of APOA5 polymorphisms on plasma triglyceride levels in Turks, a population with low levels of HDL cholesterol and a high prevalence of coronary artery disease. We found 15 polymorphisms, three of which were novel. Seven haplotype-tagging single nucleotide polymorphisms (SNPs) were chosen and genotyped in approximately 3,000 subjects. The rare alleles of the -1464T>C, -1131T>C, S19W, and 1259T>C SNPs were significantly associated with increased triglyceride levels (19-86 mg/dl; P < 0.05) and had clear gene-dose effects. Haplotype analysis of the nine common APOA5 haplotypes revealed significant effects on triglyceride levels (P < 0.001). Detailed analysis of haplotypes clearly showed that the -1464T>C polymorphism had no effect by itself but was a marker for the -1131T>C, S19W, and 1259T>C polymorphisms. The -1131T>C and 1259T>C polymorphisms were in a strong but incomplete linkage disequilibrium and appeared to have independent effects. Thus, the APOA5 -1131T>C, S19W, and 1259T>C rare alleles were associated with significant increases in plasma triglyceride levels. At least one of these alleles was present in approximately 40% of the Turks. Similar associations were observed for -1131T>C and S19W in white Americans living in San Francisco, California.

The Association of Polymorphisms in Leptin/Leptin Receptor Genes and Ghrelin/Ghrelin Receptor Genes With Overweight/Obesity and the Related Metabolic Disturbances: A Review

PubMed Central

Ghalandari, Hamid; Hosseini-Esfahani, Firoozeh; Mirmiran, Parvin

2015-01-01

Context: Leptin and ghrelin are two important appetite and energy balance-regulating peptides. Common polymorphisms in the genes coding these peptides and their related receptors are shown to be associated with body weight, different markers of obesity and metabolic abnormalities. This review article aims to investigate the association of common polymorphisms of these genes with overweight/obesity and the metabolic disturbances related to it. Evidence Acquisition: The keywords leptin, ghrelin, polymorphism, single-nucleotide polymorphism (SNP), obesity, overweight, Body Mass Index, metabolic syndrome, and type 2 diabetes mellitus (T2DM) (MeSH headings) were used to search in the following databases: Pubmed, Sciencedirect (Elsevier), and Google scholar. Overall, 24 case-control studies, relevant to our topic, met the criteria and were included in the review. Results: The most prevalent leptin/leptin receptor genes (LEP/LEPR) and ghrelin/ghrelin receptor genes (GHRL/GHSR) single nucleotide polymorphisms studied were LEP G-2548A, LEPR Q223R, and Leu72Met, respectively. Nine studies of the 17 studies on LEP/LEPR, and three studies of the seven studies on GHRL/GHSR showed significant relationships. Conclusions: In general, our study suggests that the association between LEP/LEPR and GHRL/GHSR with overweight/obesity and the related metabolic disturbances is inconclusive. These results may be due to unidentified gene-environment interactions. More investigations are needed to further clarify this association. PMID:26425125

The effects of three factor VII polymorphisms on factor VII coagulant levels in healthy Singaporean Chinese, Malay and Indian newborns.

PubMed

Quek, S C; Low, P S; Saha, N; Heng, C K

2006-11-01

Factor VII (FVII) is an independent risk factor for coronary artery disease. Three polymorphisms of the factor VII gene (F7) were studied in a group of healthy newborns comprising 561 Chinese, 398 Malays and 226 Asian Indians from Singapore. The allele frequencies of 3 polymorphisms (R353Q, Promoter 0/10bp Del/Ins and Intron 7) in the FVII gene were ascertained through genotyping by polymerase chain reaction and restriction digestion of amplified fragments. In Chinese the minor allele frequencies are Q: 0.04, Ins: 0.03, R7: 0.44; Malays, Q: 0.06, Ins: 0.10, R7: 0.41; and Indians, Q: 0.25, Ins: 0.23, R7: 0.43. Strong linkage disequilibrium (Delta > 0.7) is observed between the 0/10 bp and the R353Q sites in all ethnic groups. We conclude that: (i) the prevalence of the minor Q and Ins alleles of the R353Q and 0/10 bp polymorphisms are significantly higher in the Indian newborns than the Chinese and Malays; (ii) the Q allele is significantly associated (p = 0.01) with a lower plasma FVII coagulant level in the Indian and Malay neonates; and this polymorphism explains up to 3.8% of the variance in FVII coagulant levels; (iii) there is no significant difference in allele frequencies of the three polymorphisms between neonates with and without family histories of CAD.

Fibromyalgia, mood disorders, and intense creative energy: A1AT polymorphisms are not always silent.

PubMed

Schmechel, Donald E; Edwards, Christopher L

2012-12-01

Persons with single copies of common alpha-1-antitrypsin polymorphisms such as S and Z are often considered "silent carriers". Published evidence however supports a complex behavioral phenotype or trait - intense creative energy ("ICE")-associated with A1AT polymorphisms. We now confirm that phenotype and present an association of fibromyalgia syndrome (FMS) and A1AT in a consecutive series of neurological patients. This is a retrospective case control series of 3176 consecutive patients presenting to Duke University Memory Clinic (747 patients) and to regional community-based Caldwell Hospital Neurology and Memory center (2429 patients). Work-up included medical history and examination, psychological evaluation, and genetic analysis. Chronic widespread pain (CWP) or FMS were diagnosed according to clinical guidelines, mostly as secondary diagnoses. Neurological patients carrying A1AT polymorphisms were common (ca 16% prevalence) and carriers had significantly higher use of inhaler and anxiolytic medications. Patients with ICE phenotype had a significantly higher proportion of A1AT polymorphisms (42%) compared to non-ICE patients (13%). Presence of CWP or FMS was common (14-22%) with average age at presentation of 56 years old and mostly female gender (82%). Patients with CWP/FMS had again significantly higher proportion of A1AT polymorphisms (38%) compared to other neurological patients (13%). Patients with anxiety disorders, bipolar I or bipolar II disorders or PTSD also had increased proportion of A1AT polymorphisms and significant overlap with ICE and FMS phenotype. Significant reductions in CWP/FMS prevalence are seen in apolipoprotein E4 carriers and methylene tetrahydrofolate reductase (MTHFR) mutation homozygotes. Since ICE phenotype is reported as a lifelong behavioral attribute, the presumption is that A1AT carriers have fundamental differences in brain development and inflammatory response. In support of this concept is finding those persons reporting a diagnosis of juvenile rheumatoid or idiopathic arthritis (JRA, JIA) had a significantly high proportion of A1AT polymorphisms (63%), suggesting a spectrum for JRA to later FMS presentations. Likewise, persons reporting a history of attention deficit disorder (ADD) had an increased proportion of A1AT polymorphisms (26%) compared to non-ADD persons (13%). Toxic environmental exposures are common (23%) and associated with diagnoses of PSP, PPA, FTD, FTD-PD, PD and ADVD. A1AT carriers were increased in cases of toxic exposure and PSP, PPA and FTD-PD. Our findings support the ICE behavioral phenotype for A1AT polymorphism carriers and the reported association with anxiety and bipolar spectrum disorders. We now extend that phenotype to apparent vulnerability to inflammatory muscle disease in a spectrum from JRA to fibromyalgia (FMS) and specific behavioral subsets of ADD, PTSD, and specific late onset neurological syndromes (FTD-PD and PPA). High and low risk FMS subsets can be defined using A1AT, MTHFR and APOE genotyping. Clinical diagnoses associated with A1AT polymorphisms included fibromyalgia, JRA/JIA, bipolar disorder, PTSD, primary progressive aphasia and FTDPD, but not most Alzheimer Disease subtypes. These results support an extended phenotype for A1AT mutation carriers beyond liver and lung vulnerability to selective advantages: ICE phenotype and disadvantages: fibromyalgia, affective disorders, and selected late onset neurological syndromes. Copyright © 2012 Elsevier Inc. All rights reserved.

HPV16 variants distribution in invasive cancers of the cervix, vulva, vagina, penis, and anus.

PubMed

Nicolás-Párraga, Sara; Gandini, Carolina; Pimenoff, Ville N; Alemany, Laia; de Sanjosé, Silvia; Xavier Bosch, F; Bravo, Ignacio G

2016-10-01

Human papillomavirus (HPV)16 is the most oncogenic human papillomavirus, responsible for most papillomavirus-induced anogenital cancers. We have explored by sequencing and phylogenetic analysis the viral variant lineages present in 692 HPV16-monoinfected invasive anogenital cancers from Europe, Asia, and Central/South America. We have assessed the contribution of geography and anatomy to the differential prevalence of HPV16 variants and to the nonsynonymous E6 T350G polymorphism. Most (68%) of the variance in the distribution of HPV16 variants was accounted for by the differential abundance of the different viral lineages. The most prevalent variant (above 70% prevalence) in all regions and in all locations was HPV16_A1-3, except in Asia, where HPV16_A4 predominated in anal cancers. The differential prevalence of variants as a function of geographical origin explained 9% of the variance, and the differential prevalence of variants as a function of anatomical location accounted for less than 3% of the variance. Despite containing similar repertoires of HPV16 variants, we confirm the worldwide trend of cervical cancers being diagnosed significantly earlier than other anogenital cancers (early fifties vs. early sixties). Frequencies for alleles in the HPV16 E6 T350G polymorphism were similar across anogenital cancers from the same geographical origin. Interestingly, anogenital cancers from Central/South America displayed higher 350G allele frequencies also within HPV16_A1-3 lineage compared with Europe. Our results demonstrate ample variation in HPV16 variants prevalence in anogenital cancers, which is partly explained by the geographical origin of the sample and only marginally explained by the anatomical location of the lesion, suggesting that tissue specialization is not essential evolutionary forces shaping HPV16 diversity in anogenital cancers. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

A Haplotype of Two Novel Polymorphisms in δ-Sarcoglycan Gene Increases Risk of Dilated Cardiomyopathy in Mongoloid Population

PubMed Central

Wang, Hong; Wei, Sisi; Chen, Dan; Ying, Li; Zhou, Qing; Li, Gang; Li, Joyce; Gao, Jimin; Kato, Naoya; Hu, Wei; Li, Yigang; Wang, Yuepeng

2015-01-01

The role of genetic abnormality of δ-sarcoglycan (δ-SG) gene in dilated (DCM) and hypertrophied (HCM) cardiomyopathy patients is still unfolding. In this study we first defined the promoter region and then searched for polymorphisms/mutations among the promoter, 5'-untranslated region, and the encoding exons in δ-SG gene in 104 Chinese patients with DCM, 145 with HCM, and 790 normal controls. Two novel polymorphisms were found, an 11 base-pair (bp) deletion (c.-100~-110; -) in the promoter region and a missense polymorphism of A848G resulting in p.Q283R in the highly conserved C-terminus. The prevalence of homozygous genotype -/- of c.-100~-110 was slightly higher in DCM (14.42%) and HCM patients (14.48%), as compared with normal controls (11.01%). The prevalence of genotype of 848A/G was significantly higher in DCM (6.73%; OR = 9.43; p = 0.0002), but not in HCM patients (1.38%; OR = 1.37; p = 0.62), as compared with controls (0.76%). Haplotype -_G consisting c.-100~-110 and A848G was associated with increased risk of DCM (OR = 17.27; 95%CI = 3.19–93.56; p = 0.001) but not associated with HCM (OR = 1.90; 95%CI = 0.38–9.55; p = 0.44). Co-occurrence of the genotypes -/- of c.-100~-110 and 848A/G was found in 5 patients with DCM (4.81%; OR = 39.85; p = 0.0001), none of HCM patients, and only 1 of the controls (0.13%). Both polymorphisms were also found in the Japanese population, but not in the Africans and Caucasians. C.-100~-110 resulted in a decrease of δ-SG promoter activity to 64±3% of the control level (p<0.01). Both co-immunoprecipitation and in vitro protein pull-down assays demonstrated that δ-SG-283R interacts normally to β- and γ-SG, but significantly decreased localization of β/δ/γ-SG on the plasma membrane. In conclusion, haplotype -_G composed of c.-100~-110 and A848G confers higher susceptibility to DCM in the Mongoloid population. PMID:26720722

Gene polymorphisms as risk factors for predicting the cardiovascular manifestations in Marfan syndrome. Role of folic acid metabolism enzyme gene polymorphisms in Marfan syndrome.

PubMed

Benke, Kálmán; Ágg, Bence; Mátyás, Gábor; Szokolai, Viola; Harsányi, Gergely; Szilveszter, Bálint; Odler, Balázs; Pólos, Miklós; Maurovich-Horvat, Pál; Radovits, Tamás; Merkely, Béla; Nagy, Zsolt B; Szabolcs, Zoltán

2015-10-01

Folic acid metabolism enzyme polymorphisms are believed to be responsible for the elevation of homocysteine (HCY) concentration in the blood plasma, correlating with the pathogenesis of aortic aneurysms and aortic dissection. We studied 71 Marfan patients divided into groups based on the severity of cardiovascular involvement: no intervention required (n=27, Group A); mild involvement requiring intervention (n=17, Group B); severe involvement (n=27, Group C) subdivided into aortic dilatation (n=14, Group C1) and aortic dissection (n=13, Group C2), as well as 117 control subjects. We evaluated HCY, folate, vitamin B12 and the polymorphisms of methylenetetrahydrofolate reductase (MTHFR;c.665C>T and c.1286A>C), methionine synthase (MTR;c.2756A>G) and methionine synthase reductase (MTRR;c.66A>G). Multiple comparisons showed significantly higher levels of HCY in Group C2 compared to Groups A, B, C1 and control group (p<0.0001, p<0.0001, p=0.001 and p=0.003, respectively). Folate was lower in Group C2 than in Groups A, B, C1 and control subjects (p<0.0001, p=0.02, p<0.0001 and p<0.0001, respectively). Group C2 had the highest prevalence of homozygotes for all four gene polymorphisms. Multivariate logistic regression analysis revealed that HCY plasma level was an independent risk factor for severe cardiovascular involvement (Group C; odds ratio [OR] 1.85, 95% confidence interval [CI] 1.28-2.67, p=0.001) as well as for aortic dissection (Group C2; OR 2.49, 95%CI 1.30-4.78, p=0.006). In conclusion, severe cardiovascular involvement in Marfan patients, and especially aortic dissection, is associated with higher HCY plasma levels and prevalence of homozygous genotypes of folic acid metabolism enzymes than mild or no cardiovascular involvement. These results suggest that impaired folic acid metabolism has an important role in the development and remodelling of the extracellular matrix of the aorta.

Angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism is not a risk factor for hypertension in SLE nephritis.

PubMed

Negi, Vir S; Devaraju, Panneer; Gulati, Reena

2015-09-01

SLE is a systemic autoimmune disease with high prevalence of hypertension. Around 40-75 % of SLE patients develop nephritis, a major cause of hypertension and mortality. Angiotensin-converting enzyme (ACE) maintains the blood pressure and blood volume homeostasis. An insertion/deletion (I/D) polymorphism in intron 16 of ACE gene was reported to influence the development of hypertension, nephritis, and cardiovascular diseases in different ethnic populations. Despite compelling evidence for the high prevalence of hypertension in individuals with SLE, underlying factors for its development are not well studied. With this background, we analyzed the influence of ACE insertion/deletion polymorphism on susceptibility to SLE, development of nephritis and hypertension, other clinical features and autoantibody phenotype in South Indian SLE patients. Three hundred patients with SLE and 460 age and sex similar ethnicity matched individuals were included as patients and healthy controls, respectively. The ACE gene insertion/deletion polymorphism was analyzed by PCR. Insertion (I) and deletion (D) alleles were observed to be equally distributed among patients (57 and 43 %) and controls (59 and 41 %), respectively. The mutant (D) allele did not confer significant risk for SLE (II vs. ID: p = 0.4, OR 1.15, 95 % CI 0.8-1.6; II vs. DD: p = 0.34, OR 1.22, 95 % CI 0.8-1.85). There was no association of the ACE genotype or the allele with development of lupus nephritis (II vs. ID: p = 0.19, OR 1.41, 95 % CI 0.84-2.36; II vs. DD: p = 0.41, OR 0.74, 95 % CI 0.38-1.41) or hypertension (II vs. ID: p = 0.85, OR 0.9, 95 % CI 0.43-1.8; II vs. DD: p = 0.66, OR 1.217, 95 % CI 0.5-2.8). The presence of mutant allele (D) was not found to influence any clinical features or autoantibody phenotype. The insertion/deletion polymorphism of the ACE gene is not a genetic risk factor for SLE and does not influence development of hypertension or lupus nephritis in South Indian Tamils.

Trans-species polymorphism at antimicrobial innate immunity cathelicidin genes of Atlantic cod and related species

PubMed Central

Árnason, Einar

2015-01-01

Natural selection, the most important force in evolution, comes in three forms. Negative purifying selection removes deleterious variation and maintains adaptations. Positive directional selection fixes beneficial variants, producing new adaptations. Balancing selection maintains variation in a population. Important mechanisms of balancing selection include heterozygote advantage, frequency-dependent advantage of rarity, and local and fluctuating episodic selection. A rare pathogen gains an advantage because host defenses are predominantly effective against prevalent types. Similarly, a rare immune variant gives its host an advantage because the prevalent pathogens cannot escape the host’s apostatic defense. Due to the stochastic nature of evolution, neutral variation may accumulate on genealogical branches, but trans-species polymorphisms are rare under neutrality and are strong evidence for balancing selection. Balanced polymorphism maintains diversity at the major histocompatibility complex (MHC) in vertebrates. The Atlantic cod is missing genes for both MHC-II and CD4, vital parts of the adaptive immune system. Nevertheless, cod are healthy in their ecological niche, maintaining large populations that support major commercial fisheries. Innate immunity is of interest from an evolutionary perspective, particularly in taxa lacking adaptive immunity. Here, we analyze extensive amino acid and nucleotide polymorphisms of the cathelicidin gene family in Atlantic cod and closely related taxa. There are three major clusters, Cath1, Cath2, and Cath3, that we consider to be paralogous genes. There is extensive nucleotide and amino acid allelic variation between and within clusters. The major feature of the results is that the variation clusters by alleles and not by species in phylogenetic trees and discriminant analysis of principal components. Variation within the three groups shows trans-species polymorphism that is older than speciation and that is suggestive of balancing selection maintaining the variation. Using Bayesian and likelihood methods positive and negative selection is evident at sites in the conserved part of the genes and, to a larger extent, in the active part which also shows episodic diversifying selection, further supporting the argument for balancing selection. PMID:26038731

Prevalence and Mental Health Correlates of Sleep Disruption Among Military Members Serving in a Combat Zone

DTIC Science & Technology

2014-07-01

likely yielded higher operational tempo, greater security concerns, more hazardous environ­ mental exposures, exaggerated daily operational stressors,43...Burmeister M: PER3 polymorphism and insomnia severity in alcohol dependence. Sleep 2012; 35(4): 571-7. 10. Pigeon WR. Pinquart M, Conner K: Meta

The influence of polymorphism of the MUC7 gene on the teeth and dental hygiene of students at a faculty of dentistry in Poland.

PubMed

Buczkowska-Radlińska, Jadwiga; Pol, Justyna; Szmidt, Monika; Bińczak-Kuleta, Agnieszka

2012-04-19

The aim of the study was to analyze polymorphism of the MUC7 gene and its correlation with the DMFT value and the Plaque Control Record by O'Leary. The study was carried out on 158 students of a faculty of dentistry in Poland. Students were subjected to a clinical oral examination. The status of caries was determined using the decayed, missing and filled teeth (DMFT) value. The status of dental hygiene was examined by the Plaque Control Record (PCR Plaque Index by O'Leary T, Drake R, Naylor, 1972) index. Sherlock AX, a universal kit for DNA isolation from biological tracks (A&A BIOTECHNOLOGY), was used for DNA isolation. VNTR polymorphism in the MUC7 gene was examined by polymerase chain reaction (PCR). The prevalence of the MUC7*6/*6 genotype was definitely higher than MUC7*5/*6. The distribution of prevalence of MUC7*6/*6 and MUC7*5/*6 in the control group was similar to another. The distribution of the value of the DMFT index in the group examined with MUC7*6/*6 was similar to the group with MUC7*5/*6. Statistical analysis did not show a significant correlation between genotypes of the MUC7 gene and DMFT and the Plaque Control Record index. This study does not show a correlation between the MUC7 genotypes and caries and oral hygiene of students.

Study of the association between 3111T/C polymorphism of the CLOCK gene and the presence of overweight in schoolchildren.

PubMed

Giovaninni, Nayara P; Fuly, Jeanne T; Moraes, Leonardo I; Coutinho, Thais N; Trarbach, Ericka B; Jorge, Alexander A de L; Costalonga, Everlayny F

2014-01-01

To evaluate the association between 3111T/C polymorphism of the CLOCK gene and the presence of obesity and sleep duration in children aged 6-13 years. In adults, this genetic variant has been associated with duration of sleep, ghrelin levels, weight, and eating habits. Although short sleep duration has been linked to obesity in children, no study has aimed to identify the possible molecular mechanisms of this association to date. Weight, height, and circumferences were transformed into Z-scores for age and gender. Genotyping was performed using TaqMan methodology. A questionnaire regarding hours of sleep was provided to parents. The appropriate statistical tests were performed. This study evaluated 370 children (45% males, 55% females, mean age 8.5 ± 1.5 years). The prevalence of overweight was 18%. The duration of sleep was, on average, 9.7hours, and was inversely related to age (p<0.001). Genotype distribution was: 4% CC, 31% CT, and 65% TT. There was a trend toward higher prevalence of overweight in children who slept less than nine hours (23%) when compared to those who slept more than ten hours (16%, p=0.06). Genotype was not significantly correlated to any of the assessed outcomes. The CLOCK 3111T/C polymorphism was not significantly associated with overweight or sleep duration in children in this city. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

A pilot study on predictors of brainstem raphe abnormality in patients with major depressive disorder.

PubMed

Kostić, Milutin; Munjiza, Ana; Pesic, Danilo; Peljto, Amir; Novakovic, Ivana; Dobricic, Valerija; Tosevski, Dusica Lecic; Mijajlovic, Milija

2017-02-01

Hypo/anechogenicity of the brainstem raphe (BR) structures has been suggested as a possible transcranial parenchymal sonography (TCS) marker associated with depression. The aim of this study was to analyze possible association of the abnormal BR echogenicity in patients with major depression when compared to healthy controls, and to evaluate its clinical and genetic correlates. TCS was performed in 53 patients diagnosed as major depressive disorder (MDD) without psychotic symptoms and in 54 healthy matched controls. The TCS detected BR abnormalities were significantly more frequent in MDD patients (35 out of 53; 66%) in comparison to matched controls (5 out of 56; 9%). The prevalence of short allele (s) homozygocity in the length polymorphism of the promoter region of the serotonin transporter gene (5-HTTLPR) was significantly higher in MDD patients relative to those with normal BR echogenicity. A stepwise statistical discriminant analysis revealed statistically significant separation between MDD patients with and without BR abnormalities groups based on the four predictors combined: the Hamilton Anxiety Rating Scale item 5 ("difficulty in concentration, poor memory"), presence of social phobia, s allele homozygocity of the 5-HTTLPR polymorphism, and presence of generalized anxiety disorder. Cross-sectional design and heterogenous treatment of depressed patients. Reduced BR echogenicity in at least a subgroup of MDD patients may reflect a particular phenotype, characterized by more prevalent comorbid anxiety disorders, associated with particular genetic polymorphisms and neurotransmitter(s) deficits, most probably altered serotonergic mechanisms. Copyright © 2016 Elsevier B.V. All rights reserved.

A serotonin transporter gene polymorphism predicts peripartum depressive symptoms in an at-risk psychiatric cohort.

PubMed

Binder, Elisabeth B; Newport, D Jeffrey; Zach, Elizabeth B; Smith, Alicia K; Deveau, Todd C; Altshuler, Lori L; Cohen, Lee S; Stowe, Zachary N; Cubells, Joseph F

2010-07-01

Peripartum major depressive disorder (MDD) is a prevalent psychiatric disorder with potential detrimental consequences for both mother and child. Despite its enormous health care relevance, data regarding genetic predictors of peripartum depression are sparse. The aim of this study was to investigate associations of the serotonin-transporter linked polymorphic region (5-HTTLPR) genotype with peripartum MDD in an at-risk population. Two hundred and seventy four women with a prior history of MDD were genotyped for 5-HTTLPR and serially evaluated in late pregnancy (gestational weeks 31-40), early post-partum (week 1-8) and late post-partum (week 9-24) for diagnosis of a current major depressive episode (MDE) and depressive symptom severity. 5-HTTLPR S-allele carrier status predicted the occurrence of a MDE in the early post-partum period only (OR=5.13, p=0.017). This association persisted despite continued antidepressant treatment. The 5-HTTLPR genotype may be a clinically relevant predictor of early post-partum depression in an at-risk population. Peripartum major depressive disorder is a prevalent psychiatric disorder with potential detrimental consequences for both mother and child. Despite its enormous health care relevance, data regarding genetic predictors of peripartum depression are sparse. The aim of this study was to investigate associations of the serotonin-transporter linked polymorphic region (5-HTTLPR) genotype with peripartum MDD in an at-risk population. Copyright 2009 Elsevier Ltd. All rights reserved.

Increased carrier prevalence of deficient CYP2C9, CYP2C19 and CYP2D6 alleles in depressed patients referred to a tertiary psychiatric hospital.

PubMed

Ruaño, Gualberto; Villagra, David; Rahim, Umme Salma; Windemuth, Andreas; Kocherla, Mohan; Bower, Bruce; Szarek, Bonnie L; Goethe, John W

2008-11-01

This study compared the types and carrier prevalences of clinically significant DNA polymorphisms in the cytochrome P450 (CYP450) genes CYP2C9, CYP2C19 and CYP2D6 in major depressive disorder patients with a control group of nonpsychiatrically ill, medical outpatients. We conducted a case-control study using 73 psychiatric outpatients diagnosed with depression and referred to a tertiary center, The Institute of Living (Hartford, CT, USA), for treatment resistance or intolerable side-effects to psychotropic drugs. The controls were 120 cardiovascular patients from Hartford Hospital being treated for dyslipidemia but otherwise healthy and not psychiatrically ill. DNA typing to detect polymorphisms in the genes CYP2C9, CYP2C19 and CYP2D6 was accomplished with the Tag-It™ mutation detection assay and the Luminex xMAP ® system. The percentage of individuals in psychiatric versus control groups with two wild-type alleles for CYP2C9, CYP2C19 and CYP2D6 genes, were 50 versus 74% (p < 0.001), 71 versus 73% (not statistically significant) and 36 versus 43% (trend, p < 0.2), respectively. Within the psychiatric population, 57% of individuals were carriers of non-wild-type alleles for 2-3 genes, compared with 36% in the control population (p < 0.0001). The balance, 43% in the psychiatric population and 64% in the control, were carriers of non-wild-type alleles for none or one gene. These findings reveal that clinically relevant CYP2C9 polymorphisms occur more frequently in depressed psychiatric patients than in nonpsychiatric controls. The same trend was found for polymorphisms in the CYP2D6 gene. We found a significant cumulative metabolic deficiency in the psychiatric population for combinations of the CYP2C9, CYP2C19 and CYP2D6 genes. The significant enrichment of CYP2C9-deficient alleles in the psychiatric population validates a previously reported association of this gene with the risk for depression disorders. The high prevalence of carriers with deficient and null alleles suggests that CYP450 DNA typing may play a role in the management of psychiatric patients at tertiary care institutions.

Prevalence of common disease-associated variants in Asian Indians

PubMed Central

Pemberton, Trevor J; Mehta, Niyati U; Witonsky, David; Di Rienzo, Anna; Allayee, Hooman; Conti, David V; Patel, Pragna I

2008-01-01

Background Asian Indians display a high prevalence of diseases linked to changes in diet and environment that have arisen as their lifestyle has become more westernized. Using 1200 genome-wide polymorphisms in 432 individuals from 15 Indian language groups, we have recently shown that: (i) Indians constitute a distinct population-genetic cluster, and (ii) despite the geographic and linguistic diversity of the groups they exhibit a relatively low level of genetic heterogeneity. Results We investigated the prevalence of common polymorphisms that have been associated with diseases, such as atherosclerosis (ALOX5), hypertension (CYP3A5, AGT, GNB3), diabetes (CAPN10, TCF7L2, PTPN22), prostate cancer (DG8S737, rs1447295), Hirschsprung disease (RET), and age-related macular degeneration (CFH, LOC387715). In addition, we examined polymorphisms associated with skin pigmentation (SLC24A5) and with the ability to taste phenylthiocarbamide (TAS2R38). All polymorphisms were studied in a cohort of 576 India-born Asian Indians sampled in the United States. This sample consisted of individuals whose mother tongue is one of 14 of the 22 "official" languages recognized in India as well as individuals whose mother tongue is Parsi, a cultural group that has resided in India for over 1000 years. Analysis of the data revealed that allele frequency differences between the different Indian language groups were small, and interestingly the variant alleles of ALOX5 g.8322G>A and g.50778G>A, and PTPN22 g.36677C>T were present only in a subset of the Indian language groups. Furthermore, a latitudinal cline was identified both for the allele frequencies of the SNPs associated with hypertension (CYP3A5, AGT, GNB3), as well as for those associated with the ability to taste phenylthiocarbamide (TAS2R38). Conclusion Although caution is warranted due to the fact that this US-sampled Indian cohort may not represent a random sample from India, our results will hopefully assist in the design of future studies that investigate the genetic causes of these diseases in India. Our results also support the inclusion of the Indian population in disease-related genetic studies, as it exhibits unique genotype as well as phenotype characteristics that may yield new insights into the underlying causes of common diseases that are not available in other populations. PMID:18248681

Association of TNF polymorphisms with sarcoidosis, its prognosis and tumour necrosis factor (TNF)-α levels in Asian Indians

PubMed Central

Sharma, S; Ghosh, B; Sharma, S K

2008-01-01

Tumour necrosis factor (TNF)-α, an important proinflammatory cytokine, has been implicated in the pathogenesis of sarcoidosis, a multi-systemic granulomatous disorder of unknown aetiology. Here, we report for the first time the association of TNF haplotypes and genotypes with sarcoidosis and its prognosis in the Indian population. Five potentially functional promoter polymorphisms in the TNFA gene and a LTA_NcoI polymorphism (+252 position) of the LTA gene were genotyped in a clinically well-defined cohort of North-Indian patients with sarcoidosis (n = 96) and their regional controls (n = 155). Serum TNF-α (sTNF-α) and serum angiotensin converting enzyme (SACE) levels were measured and correlated with genotypes and haplotypes. The TNFA_-1031 and TNFA_-863 polymorphisms were identified as markers for disease onset (FET P = 0·006 and 0·042 for TNFA_-1031 and TNFA_-863, respectively). Additionally, the allele A of LTA_NcoI polymorphism was shown to be prevalent in the ‘no treatment’ group (FET P = 0·005), while the G allele was associated with frequent relapses on drug withdrawal (P = 0·057). Furthermore, the TNFA-308G>A and the TNFA-238G>A polymorphisms were found to influence sTNF-α (P = 0·054 and 0·0005, respectively) and SACE levels (P = 0·0017 and 0·056, respectively). The haplotype frequencies were significantly different in the patients and the controls (P = 0·0067). The haplotype GTCCGG was identified as the major risk/susceptibility haplotype (P = 0·003) and was associated with increased SACE levels in the patient population. In conclusion, our study suggests an association of TNF polymorphisms with sarcoidosis. PMID:18062795

Interleukin-1 gene cluster variants in hemodialysis patients with end stage renal disease: An association and meta-analysis

PubMed Central

Tripathi, G.; Rangaswamy, D.; Borkar, M.; Prasad, N.; Sharma, R. K.; Sankhwar, S. N.; Agrawal, S.

2015-01-01

We evaluated whether polymorphisms in interleukin (IL-1) gene cluster (IL-1 alpha [IL-1A], IL-1 beta [IL-1B], and IL-1 receptor antagonist [IL-1RN]) are associated with end stage renal disease (ESRD). A total of 258 ESRD patients and 569 ethnicity matched controls were examined for IL-1 gene cluster. These were genotyped for five single-nucleotide gene polymorphisms in the IL-1A, IL-1B and IL-1RN genes and a variable number of tandem repeats (VNTR) in the IL-1RN. The IL-1B − 3953 and IL-1RN + 8006 polymorphism frequencies were significantly different between the two groups. At IL-1B, the T allele of − 3953C/T was increased among ESRD (P = 0.0001). A logistic regression model demonstrated that two repeat (240 base pair [bp]) of the IL-1Ra VNTR polymorphism was associated with ESRD (P = 0.0001). The C/C/C/C/C/1 haplotype was more prevalent in ESRD = 0.007). No linkage disequilibrium (LD) was observed between six loci of IL-1 gene. We further conducted a meta-analysis of existing studies and found that there is a strong association of IL-1 RN VNTR 86 bp repeat polymorphism with susceptibility to ESRD (odds ratio = 2.04, 95% confidence interval = 1.48-2.82; P = 0.000). IL-1B − 5887, +8006 and the IL-1RN VNTR polymorphisms have been implicated as potential risk factors for ESRD. The meta-analysis showed a strong association of IL-1RN 86 bp VNTR polymorphism with susceptibility to ESRD. PMID:25684870

Association among oral health, apical periodontitis, CD14 polymorphisms, and coronary heart disease in middle-aged adults.

PubMed

Pasqualini, Damiano; Bergandi, Loredana; Palumbo, Luigi; Borraccino, Alberto; Dambra, Valentina; Alovisi, Mario; Migliaretti, Giuseppe; Ferraro, Gaetana; Ghigo, Dario; Bergerone, Serena; Scotti, Nicola; Aimetti, Mario; Berutti, Elio

2012-12-01

There is evidence to suggest that an association exists between oral infections and coronary heart disease (CHD). Subjects presenting lesions of endodontic origin (LEOs) or pulpal inflammation had an increased risk of developing CHD. However, findings concerning systemic manifestations of apical periodontitis (AP) remain controversial. An association between CD14 gene polymorphisms and atherosclerosis-associated diseases has been shown, but there are no data regarding an association between CD14 polymorphism and AP. This study evaluated associations between clinical oral health status, CD14 polymorphisms, and CHD. A case-controlled clinical trial was designed to compare middle-aged adults with acute myocardial infarction or unstable angina (n = 51) within 12 months of the acute event defined as first manifestation with healthy controls (n = 49). Participants were matched for age, sex, and socioeconomic status. Indicators of oral disease and compliance were evaluated. CD14 polymorphisms were analyzed by restriction fragment length polymorphism-polymerase chain reaction. CHD subjects had a higher prevalence of oral diseases and lower compliance to oral preventive strategies than healthy controls. Multivariate analysis showed a positive association between missing teeth (odds ratio [OR] = 1.37; 95% confidence interval [CI], 1.02-1.85), the number of LEOs (OR = 4.37; 95% CI, 1.69-11.28), chronic periodontitis (OR = 5.87; 95% CI, 1.17-29.4), and CHD. No statistically significant association emerged between the CD14 C(-260)T and the CD14 C(-159)T polymorphism, endodontic or periodontal disease, and CHD. Chronic oral diseases may increase the risk of CHD and may be an unconventional risk factor for CHD. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms and the risk of acute lymphoblastic leukemia (ALL) in Filipino children.

PubMed

Alcasabas, Patricia; Ravindranath, Yaddanapudi; Goyette, Gerard; Haller, Andrew; Del Rosario, Luz; Lesaca-Medina, Maria Ysabel; Darga, Linda; Ostrea, Enrique M; Taub, Jeffrey W; Everson, Richard B

2008-08-01

5,10-Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism. Polymorphisms at the C677T and A1298C loci are associated with reduced activity; consequently more folate substrates are shunted toward thymidylate and DNA synthesis. Several studies have reported a reduced risk of developing ALL in children with MTHFR polymorphisms. The objective of this study was to determine the association between MTHFR polymorphisms and ALL in Filipino children. We conducted a case control study in children diagnosed with ALL at the Philippine General Hospital from 1/2001 through 12/2005. Bone marrow aspirate slides were reviewed by two expert hematologists to verify the morphologic diagnosis of ALL. DNA was isolated from the slides and MTHFR polymorphisms, C677T and A1298C, were determined using Taqman real-time PCR. Cord blood of healthy Filipino newborns served as control. There were a total of 191 ALL and 394 controls genotyped. The distribution of C677T polymorphisms was similar in the two groups (P = 1.0). However, for A1298C, there was significantly more AC and CC genotypes in the ALL compared to controls (P = 0.02; OR 1.57; CI: 1.08-2.28). The 1298C allele frequency for the control group was 36.8% and 677T allele frequency was 9.9%. A1298C polymorphisms is associated with an increased risk for ALL in Filipino children. This may be due to a difference in leukemia biology or to a high prevalence of folate deficiency in Filipinos. Our study reiterates the gene and environment interaction in leukemogenesis.

Association among oxidized LDL levels, MnSOD, apolipoprotein E polymorphisms, and cardiovascular risk factors in a south Brazilian region population.

PubMed

Gottlieb, Maria G V; Schwanke, Carla H A; Santos, Adriana F R; Jobim, Paulo F; Müssel, Denise P; da Cruz, Ivana B M

2005-12-30

Oxidized LDL (ox-LDL) is involved in the initiation and progression of atherosclerosis. Many factors can affect the LDL oxidation such as oxidative stress. The present study tested whether ox-LDL levels would be associated with apolipoprotein E (APOE), manganese superoxide dismutase (MnSOD) Ala16Val polymorphisms, and classic cardiovascular risk factors. ox-LDL levels were measured by thiobarbituric acid-reactive substances and both polymorphisms were determined by polymerase chain reaction/restriction fragment length polymorphism in a sample of 252 subjects (70 men, 182 women, mean age, 54-85 years). Subjects with ox-LDL >or=0.5 nmol/mg apoprotein were considered the high level group (HLG, N = 82) and subjects with ox-LDL <0.5 nmol/mg apoprotein were considered the expected level group (ELG, N = 170). Classic risk factors were also evaluated. The results showed that diabetes mellitus was more prevalent in HLG, whereas other cardiovascular risk factors were similar between groups. The APOE genotype frequencies did not differ between HLG and ELG subjects. However, AA genotype from MnSOD polymorphism was more frequent in ELG (chi(2) = 8.48; P = 0.014). AV and VV subjects from ELG present highest ox-LDL levels (OR = 3.61; CI95% = 1.42-9.17) than AA. Additional analysis did not find gene-gene interactions associated with ox-LDL levels. Multivariate analysis showed that diabetes and the MnSOD polymorphism were independent factors associated with higher ox-LDL levels in HLG. The results suggest that an important framework on modulation of the redox status influenced by genetic polymorphisms could affect the cardiovascular homeostasis.

The effect of FokI vitamin D receptor polymorphism on bone mineral density in Jordanian perimenopausal women

PubMed Central

Kanan, Raed M.

2013-01-01

CONTEXT: Osteoporosis is a polygenic, multifactorial disease that is characterized by demineralization of bone, and thus presented with decreasing bone mineral mass. Vitamin D receptor (VDR) gene polymorphisms in the 3’-end region (as determined by the enzymes BsmI and ApaI) have been inconsistently associated with bone mineral mass. Another important VDR start codon polymorphism (as determined by the enzyme FokI) has been found to be related to adult bone mineral density (BMD) in pre-and post-menopausal American women. AIMS: This study aims to investigate the prevalence of the FokI VDR gene polymorphism in Jordanian perimenopausal women and study its relationship with bone mineral density. MATERIALS AND METHODS: DNA was isolated from 90 controls (Mean age = 50.41 ± 1.29 y), and 120 patients with symptomatic vertebral fractures (Mean age = 49.14 ± 3.19 y). Restriction Fragment Length Polymorphism (RFLP) analysis of FokI was performed on DNA samples. STATISTICAL ANALYSIS: Data was analyzed using SPSS v19 and Microsoft Excel 2007. RESULTS: The results showed that in controls, the FF (−0.70 ± 0.51) genotype is associated with high lumbar spine BMD Z-score as compared to Ff (−1.25 ± 0.26) and ff (−1.66 ± 0.47) genotypes (P = 0.0095). In patients, the ff genotype was associated with lower lumbar spine BMD in T-score (−2.31 ± 0.17) and Z-score (−1.56 ± 0.09) genotypes (P = 0.031). No significant association was seen in the femoral neck BMD. CONCLUSION: FokI polymorphism may be associated with low BMD in our studied population; however, further studies including other polymorphisms and large sample number are needed. PMID:24019627

Emerging role of NUDT15 polymorphisms in 6-mercaptopurine metabolism and dose related toxicity in acute lymphoblastic leukaemia.

PubMed

Singh, Minu; Bhatia, Prateek; Khera, Sanjeev; Trehan, Amita

2017-11-01

Despite more than 80% long term survival in ALL, morbidity due to drug related myelotoxicity remains high. Germline variants of thiopurine metabolizing enzymes (TPMT and ITPA) have been described which are associated with increased drug toxicity during maintenance phase, but their prevalence in different ethnic groups is variable to account for relatively high myelotoxicity incidence. NUDT15 variant (rs116855232) has been recently identified as a novel polymorphism related with thiopurine-induced leucopenia in inflammatory bowel disease and ALL. Current review highlights the scientific data on NUDT15 enzyme variant and its relation to 6-MP toxicity in various ethnic populations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evidence of transmission of Mycobacterium tuberculosis by random amplified polymorphic DNA (RAPD) fingerprinting in Taipei City, Taiwan.

PubMed Central

Harn, H J; Shen, K L; Ho, L I; Yu, K W; Liu, G C; Yueh, K C; Lee, J H

1997-01-01

AIMS: To determine, by strain identification of Mycobacterium tuberculosis, whether transmission has occurred between individuals or whether new strains are present. METHODS: A rapid protocol for random amplified polymorphic DNA (RAPD) analysis was developed. This protocol was applied to 64 strains of M tuberculosis that had been confirmed by culture and microbiological methods. RESULTS: There are five groups of M tuberculosis prevalent in Taipei city, Taiwan. The major types are groups I and III. Groups I and II had been prevalent until the end of last year when, according to our group analysis, they had been eradicated. However, group III was continuously present from the middle of 1995 to the middle of 1996, and group IV was present at the end of both years, which indicated that both groups were transmitted continuously. These clustered strains had demographic characteristics consistent with a finding of transmission tuberculosis. Also, there were 13 of 64 strains with unique RAPD fingerprints that were inferred to be due primarily to the reactivation of infection. In the drug resistance analysis, the major type represented included group III and part of group IV. CONCLUSIONS: Our preliminary data imply, not only that the prevalence of M tuberculosis in Taipei city is due to transmission rather than reactivation, but that drug resistance also may play a role in tuberculosis transmission. Images PMID:9378819

rs10767664 Gene Variant in Brain-Derived Neurotrophic Factor Is Associated with Diabetes Mellitus Type 2 in Caucasian Females with Obesity.

PubMed

de Luis, Daniel Antonio; Aller, Rocío; Izaola, Olatz; Primo, David; Romero, Enrique

2017-01-01

The role of brain-derived neurotrophic factor (BDNF) variants on diabetes prevalence, basal adipokine levels, body weight, and cardiovascular risk factors remains unclear in obese patients. This study is aimed at analyzing the effects of rs10767664 BDNF gene polymorphism on diabetes mellitus prevalence, body weight, cardiovascular risk factors, and serum adipokine levels in obese female patients. A total of 507 obese women were enrolled in a prospective way. Biochemical evaluation and anthropometric measures were recorded. The frequency of diabetes mellitus in the group of patients with non-T allele was 20.1 and 28.3% in T-allele carriers. Logistic regression showed a risk of diabetes mellitus of 1.33 (95% CI 1.17-2.08) in subjects with T allele adjusted by age and body mass index (BMI). T-allele carriers with diabetes mellitus have a higher weight, BMI, waist circumference, blood pressure, glucose, homeostasis model assessment insulin resistance (HOMA-IR), insulin, and C-reactive protein (CRP) levels than non-T-allele carriers. rs10767664 polymorphism of BDNF gene is associated with prevalence of diabetes mellitus in obese female patients. T-allele carriers with diabetes mellitus have a higher weight, fat mass, blood pressure, level of insulin, glucose, HOMA-IR, and CRP than non-T-allele carriers. © 2017 S. Karger AG, Basel.

Quinine Treatment Selects the pfnhe–1 ms4760–1 Polymorphism in Malian Patients with Falciparum Malaria

PubMed Central

Kone, Aminatou; Mu, Jianbing; Maiga, Hamma; Beavogui, Abdoul H.; Yattara, Omar; Sagara, Issaka; Tekete, Mamadou M.; Traore, Oumar B.; Dara, Antoine; Dama, Souleymane; Diallo, Nouhoum; Kodio, Aly; Traoré, Aliou; Björkman, Anders; Gil, Jose P.; Doumbo, Ogobara K.; Wellems, Thomas E.; Djimde, Abdoulaye A.

2013-01-01

Background. The mechanism of Plasmodium falciparum resistance to quinine is not known. In vitro quantitative trait loci mapping suggests involvement of a predicted P. falciparum sodium–hydrogen exchanger (pfnhe–1) on chromosome 13. Methods. We conducted prospective quinine efficacy studies in 2 villages, Kollé and Faladié, Mali. Cases of clinical malaria requiring intravenous therapy were treated with standard doses of quinine and followed for 28 days. Treatment outcomes were classified using modified World Health Organization protocols. Molecular markers of parasite polymorphisms were used to distinguish recrudescent parasites from new infections. The prevalence of pfnhe–1 ms4760–1 among parasites before versus after quinine treatment was determined by direct sequencing. Results. Overall, 163 patients were enrolled and successfully followed. Without molecular correction, the mean adequate clinical and parasitological response (ACPR) was 50.3% (n = 163). After polymerase chain reaction correction to account for new infections, the corrected ACPR was 100%. The prevalence of ms4760–1 increased significantly, from 26.2% (n = 107) before quinine treatment to 46.3% (n = 54) after therapy (P = .01). In a control sulfadoxine–pyrimethamine study, the prevalence of ms4760–1 was similar before and after treatment. Conclusions. This study supports a role for pfnhe–1 in decreased susceptibility of P. falciparum to quinine in the field. PMID:23162138

Characterization of Mycobacterium leprae Genotypes in China--Identification of a New Polymorphism C251T in the 16S rRNA Gene.

PubMed

Yuan, Youhua; Wen, Yan; You, Yuangang; Xing, Yan; Li, Huanying; Weng, Xiaoman; Wu, Nan; Liu, Shuang; Zhang, Shanshan; Zhang, Wenhong; Zhang, Ying

2015-01-01

Leprosy continues to be prevalent in some mountainous regions of China, and genotypes of leprosy strains endemic to the country are not known. Mycobacterium lepromatosis is a new species that was discovered in Mexico in 2008, and it remains unclear whether this species exists in China. Here, we conducted PCR- restriction fragment length polymorphism (RFLP) analysis to classify genotypes of 85 DNA samples collected from patients from 18 different provinces. All 171 DNA samples from skin biopsies of leprosy patients were tested for the presence of Mycobacterium leprae and Mycobacterium lepromatosis by amplifying the 16S rRNA gene using nested PCR, followed by DNA sequencing. The new species M. lepromatosis was not found among the 171 specimens from leprosy patients in 22 provinces in China. However, we found three SNP genotypes among 85 leprosy patients. A mutation at C251T in the 16S rRNA gene was found in 76% of the strains. We also found that the strains that showed the 16S rRNA C251T mutation belonged to SNP type 3, whereas strains without the point mutation belonged to SNP type 1. The SNP type 3 leprosy strains were observed in patients from both the inner and coastal regions of China, but the SNP type 1 strains were focused only in the coastal region. This indicated that the SNP type 3 leprosy strains were more prevalent than the SNP type 1 strains in China. In addition, the 16S rRNA gene sequence mutation at C251T also indicated a difference in the geographical distribution of the strains. To our knowledge, this is the first report of a new polymorphism in 16S rRNA gene in M. leprae in China. Our findings shed light on the prevalent genotypes and provide insight about leprosy transmission that are important for leprosy control in China.

Single-nucleotide polymorphism in the 5-α-reductase gene (SRD5A2) is associated with increased prevalence of metabolic syndrome in chemotherapy-treated testicular cancer survivors.

PubMed

Boer, Hink; Westerink, Nico-Derk L; Altena, Renske; Nuver, Janine; Dijck-Brouwer, D A Janneke; van Faassen, Martijn; Klont, Frank; Kema, Ido P; Lefrandt, Joop D; Zwart, Nynke; Boezen, H Marike; Smit, Andries J; Meijer, Coby; Gietema, Jourik A

2016-02-01

Chemotherapy-treated testicular cancer survivors are at risk for development of the metabolic syndrome, especially in case of decreased androgen levels. Polymorphisms in the gene encoding steroid 5-α-reductase type II (SRD5A2) are involved in altered androgen metabolism. We investigated whether single-nucleotide polymorphisms (SNPs) rs523349 (V89L) and rs9282858 (A49T) in SRD5A2 are associated with cardiometabolic status in testicular cancer survivors. In 173 chemotherapy-treated testicular cancer survivors, hormone levels and cardiometabolic status were evaluated cross-sectionally (median 5 years [range 3-20] after chemotherapy) and correlated with SNPs in SRD5A2. The metabolic syndrome was more prevalent in survivors who were homozygous or heterozygous variant for SRD5A2 rs523349 compared to wild type (33% versus 19%, P = 0.032). In particular, patients with lower testosterone levels (<15 nmol/l) and a variant genotype showed a high prevalence of the metabolic syndrome (66.7%). Mean intima-media thickness of the carotid artery and urinary albumin excretion, both markers of vascular damage, were higher in the group of survivors homozygous or heterozygous variant for rs523349 (0.62 versus 0.57 mm, P = 0.026; 5.6 versus 3.1 mg/24 h, P = 0.017, respectively). No association was found between cardiometabolic status and SNP rs9282858 in SRD5A2. Metabolic syndrome develops more frequently in testicular cancer survivors homozygous or heterozygous variant for SNP rs523349 in SRD5A2. Altered androgen sensitivity appears to be involved in the development of adverse metabolic and vascular changes in testicular cancer survivors and is a target for intervention. Copyright © 2015 Elsevier Ltd. All rights reserved.

Haptoglobin gene polymorphisms in peri-implantitis and chronic periodontitis.

PubMed

Ebadian, Ahmad R; Kadkhodazadeh, Mahdi; Naghavi, Seyed Hamid Hosseini; Torshabi, Maryam; Tamizi, Mahmood

2014-05-01

The haptoglobin-hemoglobin (Hp-Hb) complex plays a significant role in regulating immune responses and acts as a bacteriostatic agent. Haptoglobin polymorphisms result in different Hb binding affinities. This study sought to assess whether Hp 2-2 could be a genetic determinant for increasing the risk of peri-implantitis and chronic periodontitis. Of the Iranian subjects referred to the Department of Periodontics, Shahid Beheshti University, Tehran, 203 were entered into the study, including 117 patients and 86 periodontally healthy individuals. Polymerase chain reaction (PCR) was performed for genotyping. Data were analyzed by Kruskal-Wallis test using the SPSS statistics software package. The prevalence of Hp 2-2, 2-1, and 1-1 did not differ significantly between patients and healthy subjects (P > 0.05). The highest frequencies of Hp 1-1, 2-1, and 2-2 genotypes were seen in the control (7%), peri-implantitis (51%) and periodontitis (64%) groups, respectively. Haptoglobin polymorphisms may not play a role in development of peri-implantitis or chronic periodontitis among Iranians but we strongly suggest researchers to evaluate this polymorphism in further studies on larger sample sizes, different populations, and other types of periodontitis. © 2013 Wiley Publishing Asia Pty Ltd.

Hepatitis C virus genotypes in Southern Brazil.

PubMed

Krug, L P; Lunge, V R; Ikuta, N; Fonseca, A S; Cheinquer, H; Ozaki, L S; Barros, S G

1996-12-01

The prevalence of hepatitis C virus (HCV) genotypes in Southern Brazil was studied in the plasma of 100 HCV-RNA-positive patients attended in Porto Alegre, South of Brazil. Reverse transcription-polymerase chain reaction (RT-PCR) products from the 5' noncoding region were double digested with RsaI-HaeIII and BstNI-HinfI and analyzed by restriction fragment length polymorphism (RFLP). Three genotypes (1, 2 and 3) were demonstrable, the most prevalent being HCV type 1 (55 of 100 patients, 55%), followed by HCV type 3 (37 of 100 patients, 37%) and HCV type 2 (8 of 100 patients, 8%). There was an unusual high prevalence of genotype 3, in contrast to the majority of published data from the Southeast region.

PTPN22 -1123G>C polymorphism and anti-cyclic citrullinated protein antibodies in rheumatoid arthritis.

PubMed

Muñoz-Valle, José Francisco; Padilla-Gutiérrez, Jorge Ramón; Hernández-Bello, Jorge; Ruiz-Noa, Yeniley; Valle, Yeminia; Palafox-Sánchez, Claudia Azucena; Parra-Rojas, Isela; Gutiérrez-Ureña, Sergio Ramón; Rangel-Villalobos, Hector

2017-08-10

The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene encodes an important negative regulator of T-cell activation, lymphoid-specific phosphatase -Lyp- and has been associated with different autoimmune disorders. The PTPN22 -1123G>C polymorphism appears to affect the transcriptional control of this gene, but to date, the biological significance of this polymorphisms on rheumatoid arthritis (RA) risk remains unknown. We evaluate the association of PTPN22 -1123G>C polymorphism with anti-cyclic citrullinated protein antibodies (anti-CCP) and risk for RA in population from Western Mexico. A transversal analytic study, which enrolled 300 RA patients classified according to ACR-EULAR criteria and 300 control subjects (CS) was conducted. The -1123 G>C polymorphism was genotyped by PCR-RFLP. The anti-CCP antibodies levels were quantified by ELISA kit. We found a higher prevalence of homozygous PTPN22 -1123CC genotype in CS than in RA patients (OR 0.41; 95% confidence interval 0.24-0.71; P=.001), suggesting a potential protective effect against RA. Concerning anti-CCP levels, the CC genotype carriers showed the lowest median levels in RA (P<.05). The PTPN22 -1123CC genotype is a protector factor to RA in a Mexican-mestizo population and is associated with low anti-CCP antibodies. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Angiotensin-converting enzyme gene polymorphism in arrhythmogenic right ventricular dysplasia: is DD genotype helpful in predicting syncope risk?

PubMed

Ozben, Beste; Altun, Ibrahim; Sabri Hancer, Veysel; Bilge, Ahmet Kaya; Tanrikulu, Azra Meryem; Diz-Kucukkaya, Reyhan; Fak, Ali Serdar; Yilmaz, Ercument; Adalet, Kamil

2008-12-01

Arrhythmogenic right ventricular dysplasia (ARVD) is a heritable disorder characterised by fibrofatty replacement of right ventricular myocytes and increased risk of ventricular arrhythmias and sudden cardiac death. Angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism affects myocardial ACE levels. DD genotype favours myocardial fibrosis and is associated with malignant ventricular tachycardia. The aim of this study was to explore ACE gene polymorphism in ARVD patients. Twenty-nine patients with ARVD and 24 controls were included. All ARVD patients had documented sustained ventricular tachycardia. Thirteen patients had syncopal episodes. Six patients were resuscitated from sudden cardiac death. ACE gene polymorphism was identified by polymerase chain reaction technique. There was no significant difference in DD genotype frequency between ARVD patients and controls (44.8% vs. 45.8%, p=0.94). However, DD genotype frequency was significantly higher in ARVD patients with syncopal episodes compared to those without syncope (69.2% vs. 25.0%, p=0.017, odds ratio:6.750, 95% confidence interval: 1.318-34.565). DD genotype was detected in higher frequency also in patients with a family history of sudden cardiac death (66.7% vs. 39.1%,p=0.36). High prevalence of DD genotype in ARVD patients with syncope suggests that ACE I/D polymorphism might be useful in identifying high-risk patients for syncope.

Association of brain-derived neurotrophic factor valine to methionine polymorphism with sexual dysfunction following selective serotonin reuptake inhibitor treatment in female patients with major depressive disorder.

PubMed

Nazree, Nur Elia; Mohamed, Zahurin; Reynolds, Gavin P; Mohd Zain, Shamsul; Masiran, Ruziana; Sidi, Hatta; Chong, Lu Ann; Hway, Anne Yee; Adlan, Aida Syarinaz; Zainal, Nor Zuraida

2016-12-01

The occurrence of female sexual dysfunction (FSD) in patients with major depressive disorder (MDD) receiving selective serotonin reuptake inhibitors (SSRIs) treatment gives negative impacts on patients' quality of life and causes treatment discontinuation. We aimed to investigate whether genetic polymorphism of identified candidate gene is associated with FSD in our study population. This is a cross-sectional study. A total of 95 female patients with MDD who met the criteria of the study were recruited and were specifically assessed on the sexual function by trained psychiatrists. Patients' DNA was genotyped for BDNF Val66Met polymorphism using real-time polymerase chain reaction. The prevalence of FSD in this study is 31.6%. In the FSD group, patients with problematic marriage were significantly more frequent compared with patients who did not have problematic marriage (P = 0.009). Significant association was detected in the lubrication domain with BDNF Val66Met polymorphism (P = 0.030) using additive genetic model, with even stronger association when using the recessive model (P = 0.013). This study suggested that there was no significant association between BDNF Val66Met with FSD. However, this polymorphism is significantly associated with lubrication disorder in patients treated with SSRIs. © 2015 Wiley Publishing Asia Pty Ltd.

Association of the Risk of Dental Caries and Polymorphism of MBL2 rs11003125 Gene in Iranian Adults.

PubMed

Mokhtari, Mohammad Javad; Koohpeima, Fatemeh; Hashemi-Gorji, Feyzollah

2018-06-14

This case-control study aimed to investigate the effect of rs11003125 in dental caries. For this purpose, a total number of 404 individuals - from Fars Province in Iran - were studied. The technique of this research was the tetra-primer amplification-refractory mutation system (ARMS)-PCR. Dental caries prevalence among the 404 individuals was assessed by counting the number of decayed, missing, and filled teeth. In this research, individuals were divided into two groups: cases (n = 238) and controls (n = 166), and the peripheral blood samples were used to extract the genomic DNA. For genotyping of DNA, the tetra-primer ARMS-PCR method was conducted using specific primer pairs. While examining MBL2 rs11003125 polymorphism, we found significant differences in the genotype frequencies between the case and the control group. The pooled estimates indicated that the GG and GC genotypes of MBL2 rs11003125 polymorphism significantly increased, and therefore caries risk (OR = 2.40, 95% CI = 1.31-4.40, p = 0.004) under the dominant model. These findings suggested that polymorphism in MBL2 gene was associated with dental caries in Iranian adults. Further verification is needed with more ethnic groups and larger sample sizes to determine whether rs11003125 polymorphism is related to dental caries in other regions or not. © 2018 S. Karger AG, Basel.

No association of the G972S polymorphism of the insulin receptor substrate-1 gene with polycystic ovary syndrome in lean PCOS women with biochemical hyperandrogenemia.

PubMed

Marioli, Dimitra J; Koika, Vasiliki; Adonakis, George L; Saltamavros, Alexandros D; Karela, Anastasia; Armeni, Anastasia K; Tsapanos, Vasilios S; Decavalas, George O; Georgopoulos, Neoklis A

2010-06-01

The aim of the present study was to determine the prevalence and association of the G972S polymorphism of the insulin receptor substrate-1 gene (IRS-1 G972S SNP) with polycystic ovary syndrome (PCOS) and insulin resistance-related traits in a distinct phenotypic group of lean PCOS women with biochemical hyperandrogenemia, excluding obesity, which is considered to be an aggravating parameter of insulin resistance. The study included 162 women with PCOS and 122 regularly menstruating, ovulatory women as controls. Physical measurements included weight, height, fat-free mass, fat mass, systolic and diastolic blood pressure and resting heart rate. Biochemical parameters included the serum testosterone, free testosterone, androstenedione, total cholesterol, triglycerides, HDL and LDL cholesterol and glucose levels. Insulin resistance was assessed by determining fasting insulin levels, fasting glucose levels, the fasting glucose/insulin ratio, as well as the HOMA and QUICKI indexes. All DNA samples were genotyped by a PCR-restriction fragment length polymorphism (RLFP) assay. No association of the genotype frequencies of the G972S polymorphism in insulin receptor substrate-1 gene (IRS-1 G972S SNP) with PCOS phenotype and insulin resistance was detected. The G972S polymorphism of the IRS-1 gene should not be viewed as major contributor to the development of PCOS or as a causative variant for insulin resistance.

How direct competition shapes coexistence and vaccine effects in multi-strain pathogen systems.

PubMed

Gjini, Erida; Valente, Carina; Sá-Leão, Raquel; Gomes, M Gabriela M

2016-01-07

We describe an integrated modeling framework for understanding strain coexistence in polymorphic pathogen systems. Previous studies have debated the utility of neutral formulations and focused on cross-immunity between strains as a major stabilizing mechanism. Here we convey that direct competition for colonization mediates stable coexistence only when competitive abilities amongst pathogen clones satisfy certain pairwise asymmetries. We illustrate our ideas with nested SIS models of single and dual colonization, applied to polymorphic pneumococcal bacteria. By fitting the models to cross-sectional prevalence data from Portugal (before and after the introduction of a seven-valent pneumococcal conjugate vaccine), we are able to not only statistically compare neutral and non-neutral epidemiological formulations, but also estimate vaccine efficacy, transmission and competition parameters simultaneously. Our study highlights that the response of polymorphic pathogen populations to interventions holds crucial information about strain interactions, which can be extracted by suitable nested modeling. Copyright © 2015 Elsevier Ltd. All rights reserved.

Association of the -1082 G/A promoter polymorphism of interleukin-10 gene with the autoantibodies production in patients with rheumatoid arthritis.

PubMed

Nemec, Petr; Pavkova-Goldbergova, Monika; Gatterova, Jindra; Fojtik, Zdenek; Vasku, Anna; Soucek, Miroslav

2009-08-01

Interleukin-10 (IL-10) is an immunoregulatory cytokine, usually considered to mediate the downregulation of the inflammatory response in rheumatoid arthritis (RA). Some effects of IL-10 are not anti-inflammatory; for example, the activation of B cells to promote autoantibody production. Allelic polymorphisms located in the promoter region of the IL-10 gene may contribute to the regulation of autoantibodies production. To examine the putative association between the -1082 G/A polymorphism in the promoter region of the IL-10 gene and the susceptibility to disease onset and severity of RA, a total of 144 patients with RA diagnosed according to the revised criteria of the American College of Rheumatology for RA were consecutively recruited into the study. Radiographic progression of RA was scored according to the Sharp/van der Heijde method. Serum levels of rheumatoid factors (RFs) were measured by enzyme-linked immunosorbent assay. Polymerase chain reaction amplification was used for the analysis of the promoter polymorphism of the IL-10 gene. We observed significant differences in genotype distribution of the -1082 G/A polymorphism between IgM RF, IgA RF, and IgG RF positive/negative subgroups of RA patients, with higher prevalence of the GG genotype within IgM RF (Pg = 0.006), IgA RF (Pg = 0.05), and IgG RF (Pg = 0.007) negative RA patients. Results obtained in this study provide the evidence of an association between the -1082 G/A polymorphism in the IL-10 gene promoter and the production of RFs in RA patients.

RAGE polymorphisms and oxidative stress levels in Hashimoto's thyroiditis.

PubMed

Giannakou, Maria; Saltiki, Katerina; Mantzou, Emily; Loukari, Eleni; Philippou, Georgios; Terzidis, Konstantinos; Lili, Kiriaki; Stavrianos, Charalampos; Kyprianou, Miltiades; Alevizaki, Maria

2017-05-01

Polymorphisms of the receptor for advanced glycation end products (RAGE) gene have been studied in various autoimmune disorders, but not in Hashimoto's thyroiditis. Also, increased oxidative stress has been described in patients with Hashimoto's thyroiditis. The aim of this study was to investigate the possible role of two common RAGE polymorphisms (-429T>C, -374T>A) in Hashimoto's thyroiditis; in parallel, we studied oxidative stress levels. A total of 300 consecutive euthyroid women were examined and classified into three groups: Hashimoto's thyroiditis with treatment (n = 96), Hashimoto's thyroiditis without treatment (n = 109) and controls (n = 95). For a rough evaluation of oxidative stress, total lipid peroxide levels in serum were measured. The -429T>C AluI and -374T>A MfeI polymorphisms of RAGE were studied in genomic DNA. Significant association of the RAGE system with Hashimoto's thyroiditis was found only with regard to the prevalence of the -429T>C, but not with -374T>A polymorphism. The levels of oxidative stress were significantly elevated in Hashimoto's thyroiditis patients under treatment. Further analysis demonstrated that an oxidative stress cut-off value of 590 μmol/L is associated with an increased risk of progression of Hashimoto's thyroiditis from euthyroidism to hypothyroidism; this risk is further increased in carriers of the RAGE -429T>C polymorphism. Our findings indicate that both examined risk factors may be implicated in the occurrence of Hashimoto's thyroiditis, but this covers only a fraction of the pathophysiology of the disease. © 2017 Stichting European Society for Clinical Investigation Journal Foundation.

Genetic polymorphisms of superoxide dismutase-1 A251G and catalase C-262T with the risk of colorectal cancer.

PubMed

Jamhiri, Iman; Saadat, Iraj; Omidvari, Shahpour

2017-06-01

Oxidative stress is significant in numerous types of disease including cancer. To protect cells and organs against reactive oxygen species (ROS), the body has evolved an antioxidant protection system that involved in the detoxification of ROS. Single nucleotide polymorphisms (SNP) of anti-oxidative enzymes may dramatically change the activity of the encoded proteins; therefore, certain alleles can be established as risk factors for some kind of multi-factorial diseases including cancer. In present study we investigate the possible association between polymorphisms of superoxide dismutase 1 ( SOD1 , OMIM: 147450) and catalase ( CAT , OMIM: 115500) genes and the risk of colorectal cancer (CRC). The study included 204 colorectal cancer patients and 239 healthy control group matched for gender and age. Genotyping of SOD1 A251G and CAT C-262T were done by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. There was no significant association between CAT C-262T polymorphism and susceptibility to CRC (P>0.05). The carries of the G allele of SOD1 significantly showed higher prevalence in CRC patients compared with the control group (OR=1.84, 95% CI=1.13-2.98, P=0.013). We assessed the effect of combination of genotypes of the study polymorphisms on the risk of CRC. We found that the combination of AG+GG ( SOD1 ) and CC ( CAT ) increases the risk of developing CRC (OR=2.38, 95% CI=1.25-4.52, P=0.008).

Genetic polymorphisms of superoxide dismutase-1 A251G and catalase C-262T with the risk of colorectal cancer

PubMed Central

Jamhiri, Iman; Saadat, Iraj; Omidvari, Shahpour

2017-01-01

Oxidative stress is significant in numerous types of disease including cancer. To protect cells and organs against reactive oxygen species (ROS), the body has evolved an antioxidant protection system that involved in the detoxification of ROS. Single nucleotide polymorphisms (SNP) of anti-oxidative enzymes may dramatically change the activity of the encoded proteins; therefore, certain alleles can be established as risk factors for some kind of multi-factorial diseases including cancer. In present study we investigate the possible association between polymorphisms of superoxide dismutase 1 (SOD1, OMIM: 147450) and catalase (CAT, OMIM: 115500) genes and the risk of colorectal cancer (CRC). The study included 204 colorectal cancer patients and 239 healthy control group matched for gender and age. Genotyping of SOD1 A251G and CAT C-262T were done by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. There was no significant association between CAT C-262T polymorphism and susceptibility to CRC (P>0.05). The carries of the G allele of SOD1 significantly showed higher prevalence in CRC patients compared with the control group (OR=1.84, 95% CI=1.13-2.98, P=0.013). We assessed the effect of combination of genotypes of the study polymorphisms on the risk of CRC. We found that the combination of AG+GG (SOD1) and CC (CAT) increases the risk of developing CRC (OR=2.38, 95% CI=1.25-4.52, P=0.008). PMID:28775994

4G/5G and A-844G Polymorphisms of Plasminogen Activator Inhibitor-1 Associated with Glioblastoma in Iran--a Case-Control Study.

PubMed

Pooyan, Honari; Ahmad, Ebrahimi; Azadeh, Rakhshan

2015-01-01

Glioblastoma is a highly aggressive and malignant brain tumor. Risk factors are largely unknown however, although several biomarkers have been identified which may support development, angiogenesis and invasion of tumor cells. One of these biomarkers is PAI-1. 4G/5G and A-844G are two common polymorphisms in the gene promotor of PAI 1 that may be related to high transcription and expression of this gene. Studies have shown that the prevalence of the 4G and 844G allele is significantly higher in patients with some cancers and genetic disorders. We here assessed the association of 4G/5G and A-844G polymorphisms with glioblastoma cancer risk in Iranians in a case-control study. All 71 patients with clinically confirmed and 140 volunteers with no history and symptoms of glioblastoma as control group were screened for 4G/5G and A-844G polymorphisms of PAI-1, using ARMS-PCR. Genotype and allele frequencies of case and control groups were analyzed using the DeFinetti program. Our results showed significant associations between 4G/5G (p=0.01824) and A-844G (p=0.02012) polymorphisms of the PAI-1 gene with glioblastoma cancer risk in our Iranian population. The results of this study supporting an association of the PAI-1 4G/5G (p=0.01824) and A-844G (p=0.02012) polymorphisms with increasing glioblastoma cancer risk in Iranian patients.

Sparse networks of directly coupled, polymorphic, and functional side chains in allosteric proteins.

PubMed

Soltan Ghoraie, Laleh; Burkowski, Forbes; Zhu, Mu

2015-03-01

Recent studies have highlighted the role of coupled side-chain fluctuations alone in the allosteric behavior of proteins. Moreover, examination of X-ray crystallography data has recently revealed new information about the prevalence of alternate side-chain conformations (conformational polymorphism), and attempts have been made to uncover the hidden alternate conformations from X-ray data. Hence, new computational approaches are required that consider the polymorphic nature of the side chains, and incorporate the effects of this phenomenon in the study of information transmission and functional interactions of residues in a molecule. These studies can provide a more accurate understanding of the allosteric behavior. In this article, we first present a novel approach to generate an ensemble of conformations and an efficient computational method to extract direct couplings of side chains in allosteric proteins, and provide sparse network representations of the couplings. We take the side-chain conformational polymorphism into account, and show that by studying the intrinsic dynamics of an inactive structure, we are able to construct a network of functionally crucial residues. Second, we show that the proposed method is capable of providing a magnified view of the coupled and conformationally polymorphic residues. This model reveals couplings between the alternate conformations of a coupled residue pair. To the best of our knowledge, this is the first computational method for extracting networks of side chains' alternate conformations. Such networks help in providing a detailed image of side-chain dynamics in functionally important and conformationally polymorphic sites, such as binding and/or allosteric sites. © 2014 Wiley Periodicals, Inc.

Mitochondrial pathogenic mutations are population-specific.

PubMed

Breen, Michael S; Kondrashov, Fyodor A

2010-12-31

Surveying deleterious variation in human populations is crucial for our understanding, diagnosis and potential treatment of human genetic pathologies. A number of recent genome-wide analyses focused on the prevalence of segregating deleterious alleles in the nuclear genome. However, such studies have not been conducted for the mitochondrial genome. We present a systematic survey of polymorphisms in the human mitochondrial genome, including those predicted to be deleterious and those that correspond to known pathogenic mutations. Analyzing 4458 completely sequenced mitochondrial genomes we characterize the genetic diversity of different types of single nucleotide polymorphisms (SNPs) in African (L haplotypes) and non-African (M and N haplotypes) populations. We find that the overall level of polymorphism is higher in the mitochondrial compared to the nuclear genome, although the mitochondrial genome appears to be under stronger selection as indicated by proportionally fewer nonsynonymous than synonymous substitutions. The African mitochondrial genomes show higher heterozygosity, a greater number of polymorphic sites and higher frequencies of polymorphisms for synonymous, benign and damaging polymorphism than non-African genomes. However, African genomes carry significantly fewer SNPs that have been previously characterized as pathogenic compared to non-African genomes. Finding SNPs classified as pathogenic to be the only category of polymorphisms that are more abundant in non-African genomes is best explained by a systematic ascertainment bias that favours the discovery of pathogenic polymorphisms segregating in non-African populations. This further suggests that, contrary to the common disease-common variant hypothesis, pathogenic mutations are largely population-specific and different SNPs may be associated with the same disease in different populations. Therefore, to obtain a comprehensive picture of the deleterious variability in the human population, as well as to improve the diagnostics of individuals carrying African mitochondrial haplotypes, it is necessary to survey different populations independently. This article was reviewed by Dr Mikhail Gelfand, Dr Vasily Ramensky (nominated by Dr Eugene Koonin) and Dr David Rand (nominated by Dr Laurence Hurst).

Detection of a single nucleotide polymorphism in the human alpha-lactalbumin gene: implications for human milk proteins.

PubMed

Chowanadisai, Winyoo; Kelleher, Shannon L; Nemeth, Jennifer F; Yachetti, Stephen; Kuhlman, Charles F; Jackson, Joan G; Davis, Anne M; Lien, Eric L; Lönnerdal, Bo

2005-05-01

Variability in the protein composition of breast milk has been observed in many women and is believed to be due to natural variation of the human population. Single nucleotide polymorphisms (SNPs) are present throughout the entire human genome, but the impact of this variation on human milk composition and biological activity and infant nutrition and health is unclear. The goals of this study were to characterize a variant of human alpha-lactalbumin observed in milk from a Filipino population by determining the location of the polymorphism in the amino acid and genomic sequences of alpha-lactalbumin. Milk and blood samples were collected from 20 Filipino women, and milk samples were collected from an additional 450 women from nine different countries. alpha-Lactalbumin concentration was measured by high-performance liquid chromatography (HPLC), and milk samples containing the variant form of the protein were identified with both HPLC and mass spectrometry (MS). The molecular weight of the variant form was measured by MS, and the location of the polymorphism was narrowed down by protein reduction, alkylation and trypsin digestion. Genomic DNA was isolated from whole blood, and the polymorphism location and subject genotype were determined by amplifying the entire coding sequence of human alpha-lactalbumin by PCR, followed by DNA sequencing. A variant form of alpha-lactalbumin was observed in HPLC chromatograms, and the difference in molecular weight was determined by MS (wild type=14,070 Da, variant=14,056 Da). Protein reduction and digestion narrowed the polymorphism between the 33rd and 77th amino acid of the protein. The genetic polymorphism was identified as adenine to guanine, which translates to a substitution from isoleucine to valine at amino acid 46. The frequency of variation was higher in milk from China, Japan and Philippines, which suggests that this polymorphism is most prevalent in Asia. There are SNPs in the genome for human milk proteins and their implications for protein bioactivity and infant nutrition need to be considered.

Role of treatment-modifying MTHFR677C>T and 1298A > C polymorphisms in metformin-treated Puerto Rican patients with type-2 diabetes mellitus and peripheral neuropathy

PubMed Central

Jiménez-Ramírez, Francisco J.; Castro, Liza M.; Ortiz, Clarymar; Concepción, Jennifer; Renta, Jessicca Y.; Morales-Borges, Raúl H.; Miranda-Massari, Jorge R.; Duconge, Jorge

2017-01-01

Background The study was conducted to investigate potential association between MTHFR genotypes and diabetic peripheral neuropathy (DPN) in Puerto Ricans with type-2 diabetes mellitus (T2DM) treated with metformin. The prevalence of major MTHFR polymorphisms in this cohort was also ascertained. Methods DNAs from 89 metformin-treated patients with T2DM and DPN were genotyped using the PCR-based RFLP assay for MTHFR677C > T and 1298A > C polymorphisms. Frequency distributions of these variants in the study cohort were compared to those reported for three reference populations (HapMap project) and controls (400 newborn specimens). Chi-square (or Fischer’s exact) tests and odds ratios (OR) were used to assess association with DPN susceptibility risk (patients vs. controls) and biochemical markers (wild types vs. carriers). Results Sixty-seven percent (67%) of participants carry at least one of these MTHFR polymorphisms. No deviations from Hardy-Weinberg equilibrium were detected. The genotype and allele frequencies showed statistically significant differences between participants and controls (p < 0.0001 and p = 0.03, respectively). Results suggest that 1298A > C but not 677C > T is associated with DPN susceptibility in this cohort (p = 0.018). Different patterns of allelic dissimilarities are observed when comparing our cohort vs. the three parental ancestries. After sorting individuals by their carrier status, no significant associations were observed between these genetic variants (independently or combined) and any of the biochemical markers (HbA1c, folate, vitamin B12, homocysteine). Conclusions Prevalence of major MTHFR variants in Puerto Rican patients with T2DM is first time ever reported. The study provides further evidence on the use of this genetic marker as an independent risk factor for DPN. PMID:28231061

Polymorphisms in IL-10 and INF-γ genes are associated with early atherosclerosis in coronary but not in carotid arteries: A study of 122 autopsy cases of young adults.

PubMed

Esperança, José Carlos P; Miranda, William R R; Netto, José B; Lima, Fabiane S; Baumworcel, Leonardo; Chimelli, Leila; Silva, Rosane; Ürményi, Turán P; Cabello, Pedro H; Rondinelli, Edson; Faffe, Débora S

2015-06-01

Atherosclerosis is a complex disease, involving both genetic and environmental factors. However, the influence of genetic variations on its early development remains unclear. This study examined the association of 12 different polymorphisms with atherosclerosis severity in anterior descending coronary (DA, n = 103) and carotid arteries (CA, n = 66) of autopsied young adults (< 30 years old). Histological sections (H-E) were classified according to the American Heart Association. Polymorphisms in ACE, TNF-α (- 308G/A and - 238 G/A), IFN-γ (+ 874 A/T), MMP-9 (- 1562 C/T), IL-10 (- 1082 A/G and - 819 C/T), NOS3 (894 G/T), ApoA1 (rs964184), ApoE (E2E3E4 isoforms), and TGF-β (codons 25 and 10) genes were genotyped by gel electrophoresis or automatic DNA sequencing. Firearm projectile or car accident was the main cause of death, and no information about classical risk factors was available. Histological analysis showed high prevalence of type III atherosclerotic lesions in both DA (69%) and CA (39%) arteries, while severe type IV and V lesions were observed in 14% (DA) and 33% (CA). Allele frequencies and genotype distributions were determined. Among the polymorphisms studied, IFN-γ and IL-10 (- 1082 A/G) were related to atherosclerosis severity in DA artery. No association between genotypes and lesion severity was found in CA. In conclusion, we observed that the high prevalence of early atherosclerosis in young adults is associated with IFN-γ (p < 0.001) and IL-10 (p = 0.013) genotypes. This association is blood vessel dependent. Our findings suggest that the vascular system presents site specialization, and specific genetic variations may provide future biomarkers for early disease identification.

Association between polymorphisms in renin-angiotensin system genes and primary ovarian insufficiency in Korean women.

PubMed

Jung, Yong Wook; Jeon, Young Joo; Park, Hye Mi; Lee, Bo Eun; Rah, Hyungchul; Lee, Woo Sik; Yoon, Tae Ki; Kim, Nam Keun

2013-05-01

The purpose of this study was to evaluate the relationship between angiotensin-converting enzyme (ACE; insertion/deletion), angiotensinogen (AGT M235T), and angiotensin II type 1 receptor (AT1R 1166A>C) and the prevalence of primary ovarian insufficiency (POI) in Korean women. A total of 133 women with POI and 238 controls were genotyped for polymorphic sites in each gene using polymerase chain reaction-restriction fragment length polymorphism analysis. ACE ID and ID + II variants occurred more frequently in women with POI than in controls (odds ratio [OR], 1.830; 95% CI, 1.040-3.221; P = 0.040; and OR, 1.797; 95% CI, 1.055-3.060; P = 0.031, respectively). The AT1R 1166AC genotype occurred more frequently in participants with POI than in controls (OR, 3.171; 95% CI, 1.562-6.436; P = 0.002). Comparing the combined genotype frequencies of ACE/AT1R revealed that the frequencies of ID/AA, ID/AC, and II/AC were higher in participants than in controls (OR, 1.916; 95% CI, 1.053-3.485; P = 0.043; OR, 3.544; 95% CI, 1.207-10.407; P = 0.036; and OR, 7.875; 95% CI, 2.224-27.881; P = 0.001, respectively). The TT/AC genotype for combined genotyping of AGT/AT1R was more frequently observed in the POI group than in the control group (OR, 3.472; 95% CI, 1.450-8.313; P = 0.006). In multifactor dimensionality reduction-based haplotype analysis, the I-T-C genotype of ACE/AGT/AT1R was a possible predisposing factor for POI (OR, 4.678; 95% CI, 1.721-12.717; P = 0.002). This study demonstrates that polymorphisms in the renin-angiotensin system are related to the prevalence of POI. Thus, these renin-angiotensin system genes may serve as a novel marker for predicting the development of POI.

Vancomycin modifies the expression of the agr system in multidrug-resistant Staphylococcus aureus clinical isolates

PubMed Central

Cázares-Domínguez, Vicenta; Ochoa, Sara A.; Cruz-Córdova, Ariadnna; Rodea, Gerardo E.; Escalona, Gerardo; Olivares, Alma L.; Olivares-Trejo, José de Jesús; Velázquez-Guadarrama, Norma; Xicohtencatl-Cortes, Juan

2015-01-01

Staphylococcus aureus is an opportunistic pathogen that colonizes human hosts and causes a wide variety of diseases. Two interacting regulatory systems called agr (accessory gene regulator) and sar (staphylococcal accessory regulator) are involved in the regulation of virulence factors. The aim of this study was to evaluate the effect of vancomycin on hld and spa gene expression during the exponential and post-exponential growth phases in multidrug-resistant (MDR) S. aureus. Methods: Antibiotic susceptibility was evaluated by the standard microdilution method. The phylogenetic profile was obtained by pulsed-field gel electrophoresis (PFGE). Polymorphisms of agr and SCCmec (staphylococcal cassette chromosome mec) were analyzed by multiplex polymerase chain reaction (PCR). The expression levels of hld and spa were analyzed by reverse transcription-PCR. An enzyme-linked immunosorbent assay (ELISA) was performed to detect protein A, and biofilm formation was analyzed via crystal violet staining. Results: In total, 60.60% (20/33) of S. aureus clinical isolates were MDR. Half (10/20) of the MDR S. aureus isolates were distributed in subcluster 10, with >90% similarity among them. In the isolates of this subcluster, a high prevalence (100%) for the agrII and the cassette SCCmec II polymorphisms was found. Our data showed significant increases in hld expression during the post-exponential phase in the presence and absence of vancomycin. Significant increases in spa expression, protein A production and biofilm formation were observed during the post-exponential phase when the MDR S. aureus isolates were challenged with vancomycin. Conclusion: The polymorphism agrII, which is associated with nosocomial isolates, was the most prevalent polymorphism in MDR S. aureus. Additionally, under our study conditions, vancomycin modified hld and spa expression in these clinical isolates. Therefore, vancomycin may regulate alternative systems that jointly participate in the regulation of these virulence factors. PMID:25999924

Salmonella enterica serovar Kentucky isolates from dairy cows and poultry demonstrate different evolutionary histories and host-specific polymorphisms

USDA-ARS?s Scientific Manuscript database

Salmonella enterica subsp. enterica serovar Kentucky is commonly isolated from dairy cows and poultry in the United States. Although it is not among the most frequently isolated serovars from cases of human salmonellosis, its high prevalence in livestock and poultry indicate it is a potential public...

Has enhanced folate status during pregnancy altered natural selection and possibly Autism prevalence? A closer look at a possible link.

PubMed

Rogers, Eugene J

2008-09-01

The inverse association between maternal folate status and incidence of infants born with neural tube defects (NTD's) was recognized over twenty years ago and led the US health agencies in the early 1990s to recommend that women of childbearing age consume 400 microg of folic acid each day. The FDA followed by mandating that certain foods be fortified with folic acid and this has resulted in a significant enhancement of maternal folate status to levels that are often difficult to otherwise achieve naturally. At least one study indicates that this has decreased the incidence of NTD's. However, this same time period directly coincides with what many feel is the apparent beginning and continuous increase in the prevalence of Autism and related Autism Spectrum Disorders (ASD's) in the US. Are these similar time frames of changes in maternal folate status and possible Autism prevalence a random event or has improved maternal (and fetal) folate status during pregnancy played a role? It is not only plausible but highly likely. A particular polymorphic form to a key enzyme required to activate folate for methylation in neurodevelopment, 5-methylenetetrahydrofolate reductase (MTHFR), demonstrates reduced activity under low or normal folate levels but normal activity under conditions of higher folate nutritional status. A consequence of the presence of the polymorphic form of this enzyme during normal or reduced folate status are higher plasma homocysteine levels than noncarriers and the combination of these factors have been shown in several studies to result in an increase rate of miscarriage via thrombotic events. However, the incidence of hyperhomocysteinemia in the presence of the polymorphism is reduced under the common condition of enhanced folate status and thereby masks the latent adverse effects of the presence of this enzyme form during pregnancy. Of great importance is that this polymorphism, although common in the normal population, is found in significantly higher frequency in Autisic individuals. It is hypothesized here that the enhancement of maternal folate status before and during pregnancy in the last 15 years has altered natural selection by increasing survival rates during pregnancy of infants possessing the MTHFR C677T polymorphism, via reduction in hyperhomocysteinemia associated with this genotype and thereby miscarriage rates. This also points directly to an increased rate of births of infants with higher postnatal requirements for folic acid needed for normal methylation during this critical neurodevelopmental period. If these numbers have increased then so have the absolute number of infants that after birth fail to maintain the higher folate status experienced in utero thus leading to an increased number of cases of developmental disorders such as Autism. Detection of the C677T polymorphism as well as other methionine cycle enzymes related to folate metabolism and methylation at birth as part of newborn screening programs could determine which newborns need be monitored and maintained on diets or supplements that ensure adequate folate status during this critical postnatal neurodevelopment period.

Prevalence, Patterns, and Genetic Association Analysis of Modic Vertebral Endplate Changes.

PubMed

Kanna, Rishi Mugesh; Shanmuganathan, Rajasekaran; Rajagopalan, Veera Ranjani; Natesan, Senthil; Muthuraja, Raveendran; Cheung, Kenneth Man Chee; Chan, Danny; Kao, Patrick Yu Ping; Yee, Anita; Shetty, Ajoy Prasad

2017-08-01

A prospective genetic association study. The etiology of Modic changes (MCs) is unclear. Recently, the role of genetic factors in the etiology of MCs has been evaluated. However, studies with a larger patient subset are lacking, and candidate genes involved in other disc degeneration phenotypes have not been evaluated. We studied the prevalence of MCs and genetic association of 41 candidate genes in a large Indian cohort. MCs are vertebral endplate signal changes predominantly observed in the lumbar spine. A significant association between MCs and lumbar disc degeneration and nonspecific low back pain has been described, with the etiopathogenesis implicating various mechanical, infective, and biochemical factors. We studied 809 patients using 1.5-T magnetic resonance imaging to determine the prevalence, patterns, distribution, and type of lumbar MCs. Genetic association analysis of 71 single nucleotide polymorphisms (SNPs) of 41 candidate genes was performed based on the presence or absence of MCs. SNPs were genotyped using the Sequenome platform, and an association test was performed using PLINK software. The mean age of the study population (n=809) was 36.7±10.8 years. Based on the presence of MCs, the cohort was divided into 702 controls and 107 cases (prevalence, 13%). MCs were more commonly present in the lower (149/251, 59.4%) than in the upper (102/251, 40.6%) endplates. L4-5 endplates were the most commonly affected levels (30.7%). Type 2 MCs were the most commonly observed pattern (n=206, 82%). The rs2228570 SNP of VDR ( p =0.02) and rs17099008 SNP of MMP20 ( p =0.03) were significantly associated with MCs. Genetic polymorphisms of SNPs of VDR and MMP20 were significantly associated with MCs. Understanding the etiopathogenetic mechanisms of MCs is important for planning preventive and therapeutic strategies.

IL28B gene polymorphism rs12979860, but not rs8099917, contributes to the occurrence of chronic HCV infection in Uruguayan patients.

PubMed

Echeverría, Natalia; Chiodi, Daniela; López, Pablo; Sanchez Ciceron, Adriana; Angulo, Jenniffer; López-Lastra, Marcelo; Silvera, Paola; Canavesi, Adrian; Bianchi, Carla; Colistro, Valentina; Cristina, Juan; Hernandez, Nelia; Moreno, Pilar

2018-03-02

Host single-nucleotide polymorphisms (SNPs) near the interleukin 28B (IL28B) locus are associated with sustained virological response to antiviral therapy and with spontaneous Hepatitis C Virus (HCV) clearance. Prevalence of these SNPs varies depending on ethnicity. The impact of IL28B SNPs in HCV-infected patients is currently unknown in Uruguay. Therefore, the aim of this study was to evaluate and compare the distribution of polymorphisms in the IL28B gene (rs12979860 and rs8099917) among HCV-infected patients and healthy individuals in Uruguay and thus assess their possible association with the establishment of HCV infection. DNA was recovered from 92 non-infected individuals and 78 HCV-infected patients and SNPs were determined by RFLP and allelic discrimination by real-time PCR. The distribution of rs12979860 genotypes for the infected population was 29.5%-CC, 47.4%-CT and 23.1%-TT and for the control group 45.7%, 42.4% and 11.9%, respectively. Prevalence in both infected and uninfected individuals is similar to that reported in other countries with admixed populations. The distribution of rs8099917 genotypes for the infected population was 57.7%-TT, 27.2%-TG and 14.1%-GG and for the control group 60.9%, 33.7% and 5.4%, respectively. The comparison of rs12979860 genotype distribution between the two populations evidenced a higher prevalence of the favourable genotype (CC) in the uninfected control group (p < 0.05). Additionally, results generated using logistic regression analysis show that individuals carrying rs12979860-TT or CT genotypes have a higher likelihood of developing chronic hepatitis upon infection with HCV, when compared to CC carriers, considering rs8099917 genotype as constant. Patients with HCV infection have a statistically significant lower prevalence of the favourable rs12979860 genotype when compared to uninfected individuals; therefore we can establish that only IL28B rs12979860-CT and TT genotypes seem to contribute to the occurrence of chronic HCV infection in the cohort of Uruguayan population studied. Considering that a trend towards a higher frequency of "good" response genotypes was observed in responder patients, we believe that IL28B rs12979860 genotyping could be a useful tool for predicting different therapies outcome, including in the DAA era.

Mutation covariation of HIV-1 CRF07_BC reverse transcriptase during antiretroviral therapy.

PubMed

Li, Zhenpeng; Huang, Yang; Ouyang, Yabo; Xing, Hui; Liao, Lingjie; Jiang, Shibo; Shao, Yiming; Ma, Liying

2013-11-01

To understand the effect of HIV-1 drug resistance mutations in the context of antiretroviral therapy (ART), we compared the prevalence of protease (PR) and reverse transcriptase (RT) mutations in HIV-1 CRF07_BC sequences from blood samples of treatment-naive and ART-treated patients. Mutation covariation in the RT and PR of HIV-1 CRF07_BC viruses from 542 treatment-naive patients and 261 patients treated with lamivudine/zidovudine/nevirapine or lamivudine/zidovudine/efavirenz was analysed. Stratified networks were used to display the mutation covariation. Based on the comparison between treatment-naive and ART-treated patients, three types of featured mutations for RT and PR were initially identified: treatment-associated mutations, treatment-agonistic mutations and overlapping polymorphisms. Twelve significant covariation pairs were found between five treatment-associated mutations (K103N, M184V, Q197K, G190A and Y181C) and nine overlapping polymorphisms (A36E, D39N, Y121H, D123E, R135I, T200A, R277K, L283I and D291E). Meanwhile, three covariation pairs between three treatment-associated mutations (I132L and M184V for RT and I15V for PR) and three overlapping polymorphisms (L10I, L36M and A71V) for PR were also detected. Finally, the overlapping polymorphisms for RT and PR were both found to have significant correlations with treatment-associated mutations, indicating a possible association between polymorphisms and drug resistance. When compared with HIV-1 subtype B under the same regimens as CRF07_BC, the mutation covariations of CRF07_BC showed a distinct pattern of RT and PR mutation covariation. The role of polymorphisms in the development of drug resistance has been widely reported. Here, we found a significant correlation between overlapping polymorphisms for RT and PR and treatment-associated mutations, indicating that polymorphisms exert a global influence on treatment-associated mutations. Polymorphism mutations might therefore be considered before initiating ART to improve the efficacy of drug combinations.

Genetic associations of body composition, flexibility and injury risk with ACE, ACTN3 and COL5A1 polymorphisms in Korean ballerinas

PubMed Central

Kim, Jun Ho; Jung, Eun Sun; Kim, Chul-Hyun; Youn, Hyeon; Kim, Hwa Rye

2014-01-01

[Purpose] The purpose of this study was to exam the association of body composition, flexibility, and injury risk to genetic polymorphisms including ACE ID, ACTN3 RX, and COL5A1 polymorphisms in ballet dancers in Korea. [Methods] For the purpose of this study, elite ballerinas (n = 97) and normal female adults (n = 203) aged 18 to 39 were recruited and these participants were tested for body weight, height, body fat, fat free mass, flexibility, injury risks on the joints and gene polymorphisms (ACE, ACTN3, COL5A1 polymorphism). [Results] As results, the ACE DD genotype in ballerinas was associated with higher body fat and percentage of body fat than the ACE II and ID genotypes (p < 0.05). In the study on the ACTN3 polymorphism and ballerinas, the XX genotype in ballerinas had lower body weight and lower fat-free mass than the RR and RX genotype (p < 0.005). Also, the means of sit and reach test for flexibility was lower in the ACTN3 XX genotype of ballerinas than the RR and RX genotype of ballerinas (p < 0.05). Among the sports injuries, the ankle injury of the XX-genotyped ballerinas was in significantly more prevalence than the RR and XX-genotyped ballerinas (p < 0.05). According to the odd ratio analysis, XX-genotyped ballerinas have the injury risk on the ankle about 4.7 (95% CI: 1.6~13.4, p < 0.05) times more than the RR and RX-genotyped ballerinas. Meanwhile, the COL5A1 polymorphism in ballerinas has no association with any factors including flexibility and injury risks. [Conclusion] In conclusion, ACE polymorphism and ACTN3 polymorphism were associated with ballerinas' performance capacity; COL5A1 was not associated with any factors of performance of Ballerinas. The results suggested that the ACE DD genotype is associated with high body fat, the ACTN3 XX genotype is associated with low fat-free mass, low flexibility, and higher risk of ankle-joint injury. PMID:25566457

Genetic Polymorphisms in Cytokine Genes in Colombian Patients with Ocular Toxoplasmosis.

PubMed

Naranjo-Galvis, C A; de-la-Torre, A; Mantilla-Muriel, L E; Beltrán-Angarita, L; Elcoroaristizabal-Martín, X; McLeod, R; Alliey-Rodriguez, N; Begeman, I J; López de Mesa, C; Gómez-Marín, J E; Sepúlveda-Arias, J C

2018-04-01

Toxoplasmosis is caused by infection with the protozoan parasite Toxoplasma gondii , which has the capacity to infect all warm-blooded animals worldwide. Toxoplasmosis is a major cause of visual defects in the Colombian population; however, the association between genetic polymorphisms in cytokine genes and susceptibility to ocular toxoplasmosis has not been studied in this population. This work evaluates the associations between polymorphisms in genes coding for the cytokines tumor necrosis factor alpha (TNF-α) (rs1799964, rs1800629, rs1799724, rs1800630, and rs361525), interleukin 1β (IL-1β) (rs16944, rs1143634, and rs1143627), IL-1α (rs1800587), gamma interferon (IFN-γ) (rs2430561), and IL-10 (rs1800896 and rs1800871) and the presence of ocular toxoplasmosis (OT) in a sample of a Colombian population (61 patients with OT and 116 healthy controls). Genotyping was performed with the "dideoxynucleotide (ddNTP) primer extension" technique. Functional-effect predictions of single nucleotide polymorphisms (SNPs) were done by using FuncPred. A polymorphism in the IL-10 gene promoter (-1082G/A) was significantly more prevalent in OT patients than in controls ( P = 1.93e-08; odds ratio [OR] = 5.27e+03; 95% confidence interval [CI] = 3.18 to 8.739; Bonferroni correction [BONF] = 3.48e-07). In contrast, haplotype "AG" of the IL-10 gene promoter polymorphisms (rs1800896 and rs1800871) was present at a lower frequency in OT patients ( P = 7e-04; OR = 0.10; 95% CI = 0.03 to 0.35). The +874A/T polymorphism of IFN-γ was associated with OT ( P = 3.37e-05; OR = 4.2; 95% CI = 2.478 to 7.12; BONF = 6.07e-04). Haplotype "GAG" of the IL-1β gene promoter polymorphisms (rs1143634, rs1143627, and rs16944) appeared to be significantly associated with OT ( P = 0.0494). The IL-10, IFN-γ, and IL-1β polymorphisms influence the development of OT in the Colombian population. Copyright © 2018 American Society for Microbiology.

Apolipoprotein C3 SstI polymorphism and triglyceride levels in Asian Indians

PubMed Central

Chhabra, S; Narang, R; Krishnan, LR; Vasisht, S; Agarwal, DP; Srivastava, LM; Manchanda, SC; Das, N

2002-01-01

Background A close association between Sst I polymorphism in the 3' untranslated region of the apolipoproteinC3 (APOC3) gene and levels of plasma triglycerides (TG) had been reported by different investigators. Hypertriglyceridemia(HTG) is a known risk factor for coronary artery disease (CAD) in the context of Asian Indians. We conducted a study on the relationship between APOC3 SstI polymorphism (S1S1, S1S2 and S2S2 genotypes) and plasma TG levels in a group of 139 male healthy volunteers from Northern India. Methods DNA samples were analyzed by polymerase chain reaction (PCR) followed by SstI digestion. Digested PCR products were run on 3% agarose gel and visualized by ethidium bromide staining. Results Rare S2 allele was highly prevalent in our study population (0.313) as compared to the Caucasians (0.00–0.11). The genotypic distribution was in agreement with Hardy-Weinberg equilibrium. S2 allele was almost two times more prevalent in the HTG group (N = 34) as compared to NTG group (N = 105) (p = 0.001). Multiple logistic regression revealed S1S2 individuals had age-adjusted odds ratio of 2.43 (95%CI = 0.99–6.01, p = 0.054) and S2S2 had 9.9 (95%CI = 2.66–37.29, p = 0.0006) for developing HTG in comparison to S1S1 genotype. Conclusions Our study shows a significant association between rare S2 allele and HTG in Asian Indians. PMID:12052247

Genetic disposition and modifiable factors independently associated with anemia in patients with type 2 diabetes mellitus.

PubMed

Chiou, Terry Ting-Yu; Lee, Jong-Jer; Wang, Ming-Chung; Chung, Min-Shien; Pan, Lin-Lin; Hsieh, Ching-Jung; Huang, Siang-Ting; Chang, Hsueh-Wen; Yang, Kuender D; Lee, Chien-Te; Liu, Rue-Tsuan

2015-04-01

Anemia is prevalent but under-recognized in patients with diabetes mellitus (DM). Genetic variants in angiotensin-converting enzyme (ACE), tumor necrosis factor-alpha (TNF-α) and erythropoietin (EPO) have been associated with diabetic nephropathy. In the present study, we investigated the associations between anemia and polymorphisms in EPO promoter (rs1617640), TNF-α G-308A and ACE Insertion/Deletion in Chinese patients with type 2 diabetes. Polymorphisms in ACE, TNF-α and EPO were genotyped in 1142 patients. Anemia was defined as hemoglobin (Hb) levels below 12 g/dL for women and 13 g/dL for men. 286 (25%) patients had anemia. Patients with anemia were older, had longer duration of diabetes, worse renal function and more albuminuria. ACE Insertion/Deletion and TNF-a G-308A were not associated with anemia. The frequencies of EPO polymorphism (rs1617640) were significantly different between anemic and nonanemic patients. Patients with TT genotype had higher prevalence of anemia than those with TG and GG. Regression analysis identified EPO SNP, duration of DM, serum albumin, albuminuria and renal function independently associated with anemia. After adjusting for multiple variables, TT and TG genotypes were associated with 3-5-fold increased risk for anemia compared to GG. The EPO genotype in Chinese patients with type 2 diabetes is associated with anemia and may help to identify those at risk. Further evaluation of its effect on clinical outcomes in prospective studies may be useful to predict the outcomes of erythropoiesis stimulating therapy, and to individualize anemia management. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Naturally acquired antibody responses to recombinant Pfs230 and Pfs48/45 transmission blocking vaccine candidates.

PubMed

Jones, Sophie; Grignard, Lynn; Nebie, Issa; Chilongola, Jaffu; Dodoo, Daniel; Sauerwein, Robert; Theisen, Michael; Roeffen, Will; Singh, Shrawan Kumar; Singh, Rajesh Kumar; Singh, Sanjay; Kyei-Baafour, Eric; Tetteh, Kevin; Drakeley, Chris; Bousema, Teun

2015-07-01

Pfs48/45 and Pfs230 are Plasmodium falciparum sexual stage proteins and promising malaria transmission-blocking vaccine candidates. Antibody responses against these proteins may be naturally acquired and target antigens may be under selective pressure. This has consequences for the future evaluation of vaccine immunogenicity and efficacy in populations naturally exposed to malaria. We determined naturally acquired antibody responses to the recombinant proteins Pfs48/45-10C and Pfs230-230CMB in children from three malaria endemic settings in Ghana, Tanzania and Burkina Faso. We also examined genetic polymorphisms in the P. falciparum gene pfs48/45. Antibody prevalence was 1.1-18.2% for 10C and 6.7-18.9% for 230CMB. In Burkina Faso we observed evidence of an age-dependent acquisition pattern for both 10C (p < 0.001) and 230CMB (p = 0.031). Membrane feeding assays on a separate dataset demonstrated an association between functional transmission reducing activity and antibody prevalence for both 10C (p = 0.017) and 230CMB (p = 0.049). 17 single nucleotide polymorphisms were found in pfs48/45 (from 126 samples), with 5 non-synonymous SNPs in the Pfs48/45 10C region. We conclude there are naturally acquired antibody responses to both vaccine candidates which have functional relevance by reducing the transmissibility of infected individuals. We identified genetic polymorphisms, in pfs48/45 which exhibited geographical specificity. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Association of CRP gene polymorphism with CRP levels and Coronary Artery Disease in Type 2 Diabetes in Ahvaz, southwest of Iran

PubMed Central

Ghaffari, Mohammad Ali; Askari Sede, Saeed; Rashtchizadeh, Nadereh; Mohammadzadeh, Ghorban; Majidi, Shahla

2014-01-01

Introduction: We evaluated the association between four polymorphisms in the CRP gene with serum C-reactive protein (CRP) levels, prevalence and severity of coronary artery disease (CAD) in type 2 diabetes mellitus (T2DM) patients. Methods: We performed coronary angiography for 308 T2DM patients and classified them into two groups: T2DM with CAD and T2DM without CAD. All patients were from Ahvaz, Iran. serum levels of CRP, glucose and lipid profile were measured. Genotyping was performed by PCR/RFLP, and the severity of coronary artery disease was determined by Gensini score. Results: The GG genotype of SNP rs279421 was associated with the increased risk of CAD (OR= 2.38; 95% CI: 1.12- 5.8; p= 0.02) and CA, TT, TA genotypes and A allele of SNP rs3091244 and GA genotypes and A allele of SNP rs3093062 were significantly associated with increased CRP levels. None of genotypes or alleles was associated with Gensini score. We found that the haplotype 7 (AGCG) was associated with decreased risk of CAD (OR= 0.11; 95% CI: 0.02, 0.66; p= 0.017) and the Gensini score was correlated with increased levels of CRP, only in CAD group. Conclusion: Although genetic polymorphisms were influenced on serum RP levels, none of the alleles and genotypes raising or falling C-reactive protein levels was consistently associated with an increased prevalence of CAD or protected from that. PMID:25337466

Combined 677CC/1298AC genotypes of methylenetetrahydrofolate reductase (MTHFR ) reduce susceptibility to precursor B lymphoblastic leukemia in a Chinese population.

PubMed

Lv, Ling; Wu, Cuie; Sun, Henjuan; Zhu, Saijuan; Yang, Yongchen; Chen, Xi; Fu, Hua; Bao, Liming

2010-06-01

The methylenetetrahydrofolate reductase (MTHFR) encodes a major enzyme in folate metabolism. It has been suggested that two MTHFR polymorphisms, 677C>T and 1298A>C, influence risk of acute lymphoblastic leukemia (ALL). Most studies on relation of MTHFR polymorphisms to ALL susceptibility have been in pediatric populations because ALL is relatively rare in adults. Here, we report a case-control study of 127 Chinese patients with adult precursor B lymphoblastic leukemia (B-ALL) to examine correlation between the MTHFR polymorphisms and B-ALL susceptibility in adults. Our data show that although the prevalence of genotype 1298CC was significantly higher in the female patients than in the controls (P = 0.04), the differences in distributions of combined genotypes of 1298CC with either 677CC or 677CT between the cases and the controls were statistically insignificant. Haplotype analysis revealed no significant difference between the cases and the controls. The prevalence for joint MTHFR genotypes 677CC/1298AC was significantly lower in the female B-ALL cases than in the controls [odds ratio (OR) = 0.06, 95% CI = 0.00-0.53, P = 0.0033] and no differences among the men [OR = 0.71, 95% CI = 0.20-2.53, P = 0.55], suggesting that protective effects of combined MTHFR 677CC/1298AC genotypes on susceptibility of adult B-ALL are gender bias toward women with 677CC/1298AC women being at a 17-fold reduced odds to develop B-ALL.

A polymorphism in the gene encoding procolipase produces a colipase, Arg92Cys, with decreased function against long-chain triglycerides

PubMed Central

D’Silva, Sheryl; Xiao, Xunjun; Lowe, Mark E.

2013-01-01

Type 2 diabetes mellitus is a multifactorial and polygenic disorder with increasing prevalence. Recently, a polymorphism in the gene encoding procolipase, a cysteine for arginine substitution at position 92, was associated with type 2 diabetes in two human populations. Because procolipase plays a critical role in dietary fat metabolism, polymorphisms that affect the function of procolipase could influence the development of type 2 diabetes. We hypothesized that the Arg92Cys polymorphism has functional consequences. To test our hypothesis, we expressed recombinant cysteine 92 (Cys92) procolipase in a yeast expression system and compared the function and stability of purified Cys92 with that of the more common arginine 92 (Arg92) procolipase. Cys92 fully restored the activity of bile-salt inhibited lipase with short- and medium-chain triglycerides but only had 50% of Arg92 function with long-chain triglycerides. After storage at 4°C, Cys92 lost the ability to restore pancreatic triglyceride lipase activity with medium- and long-chain triglycerides. The loss of function correlated with the inability of Cys92 to anchor lipase on an emulsion surface and oxidation of the cysteine. No detectable degradation or intramolecular disulfide formation occurred in Cys92 after storage. Our findings demonstrate that the Arg92Cys polymorphism decreases the function of Cys92 colipase. This change may contribute to the development of type 2 diabetes. PMID:17715423

Single nucleotide polymorphism-specific regulation of matrix metalloproteinase-9 by multiple miRNAs targeting the coding exon

PubMed Central

Duellman, Tyler; Warren, Christopher; Yang, Jay

2014-01-01

Microribonucleic acids (miRNAs) work with exquisite specificity and are able to distinguish a target from a non-target based on a single nucleotide mismatch in the core nucleotide domain. We questioned whether miRNA regulation of gene expression could occur in a single nucleotide polymorphism (SNP)-specific manner, manifesting as a post-transcriptional control of expression of genetic polymorphisms. In our recent study of the functional consequences of matrix metalloproteinase (MMP)-9 SNPs, we discovered that expression of a coding exon SNP in the pro-domain of the protein resulted in a profound decrease in the secreted protein. This missense SNP results in the N38S amino acid change and a loss of an N-glycosylation site. A systematic study demonstrated that the loss of secreted protein was due not to the loss of an N-glycosylation site, but rather an SNP-specific targeting by miR-671-3p and miR-657. Bioinformatics analysis identified 41 SNP-specific miRNA targeting MMP-9 SNPs, mostly in the coding exon and an extension of the analysis to chromosome 20, where the MMP-9 gene is located, suggesting that SNP-specific miRNAs targeting the coding exon are prevalent. This selective post-transcriptional regulation of a target messenger RNA harboring genetic polymorphisms by miRNAs offers an SNP-dependent post-transcriptional regulatory mechanism, allowing for polymorphic-specific differential gene regulation. PMID:24627221

The 14 bp Del/Ins HLA-G polymorphism is related with high blood pressure in acute coronary syndrome and type 2 diabetes mellitus.

PubMed

García-González, Ilian Janet; Valle, Yeminia; Rivas, Fernando; Figuera-Villanueva, Luis Eduardo; Muñoz-Valle, José Francisco; Flores-Salinas, Hector Enrique; Gutiérrez-Amavizca, Bianca Ethel; Dávalos-Rodríguez, Nory Omayra; Padilla-Gutiérrez, Jorge Ramón

2014-01-01

Immunologic and inflammatory processes are involved in the pathogenesis of acute coronary syndrome (ACS) and type 2 diabetes mellitus (DM2). Human leukocyte antigen-G (HLA-G) is a negative regulator of the immune response. This study evaluates the 14 bp Del/Ins HLA-G polymorphism in ACS and DM2. Three hundred and seventy individuals from Western Mexico were recruited and categorized into three groups: ACS (86), DM2 without coronary complications (70), and healthy subjects (214). Genotyping of the 14 bp Del/Ins HLA-G polymorphism was performed by PCR and Native-PAGE. The most common risk factors were hypertension and overweight in ACS and DM2, respectively. The genetic distribution of the 14 bp Del/Ins HLA-G polymorphism showed no significant differences between groups (P ≥ 0.23). Nonetheless, the Ins/Ins genotype was associated with high blood pressure (HBP) in the DM2 group (OR(c) = 1.65, P = 0.02). The genetic recessive model showed similar findings (OR(c) = 3.03, P = 0.04). No association was found in ACS, with a P of 0.05; nevertheless, the prevalence of Ins/Ins carriers was quite similar to that found in the DM2-HBP group. The 14 bp Del/Ins HLA-G polymorphism was not a susceptibility factor for ACS or DM2; however, the Ins/Ins genotype might have contributed to the development of HBP in the studied groups.

The 14 bp Del/Ins HLA-G Polymorphism Is Related with High Blood Pressure in Acute Coronary Syndrome and Type 2 Diabetes Mellitus

PubMed Central

García-González, Ilian Janet; Valle, Yeminia; Rivas, Fernando; Figuera-Villanueva, Luis Eduardo; Muñoz-Valle, José Francisco; Flores-Salinas, Hector Enrique; Gutiérrez-Amavizca, Bianca Ethel; Dávalos-Rodríguez, Nory Omayra; Padilla-Gutiérrez, Jorge Ramón

2014-01-01

Immunologic and inflammatory processes are involved in the pathogenesis of acute coronary syndrome (ACS) and type 2 diabetes mellitus (DM2). Human leukocyte antigen-G (HLA-G) is a negative regulator of the immune response. This study evaluates the 14 bp Del/Ins HLA-G polymorphism in ACS and DM2. Three hundred and seventy individuals from Western Mexico were recruited and categorized into three groups: ACS (86), DM2 without coronary complications (70), and healthy subjects (214). Genotyping of the 14 bp Del/Ins HLA-G polymorphism was performed by PCR and Native-PAGE. The most common risk factors were hypertension and overweight in ACS and DM2, respectively. The genetic distribution of the 14 bp Del/Ins HLA-G polymorphism showed no significant differences between groups (P ≥ 0.23). Nonetheless, the Ins/Ins genotype was associated with high blood pressure (HBP) in the DM2 group (ORc = 1.65, P = 0.02). The genetic recessive model showed similar findings (ORc = 3.03, P = 0.04). No association was found in ACS, with a P of 0.05; nevertheless, the prevalence of Ins/Ins carriers was quite similar to that found in the DM2-HBP group. The 14 bp Del/Ins HLA-G polymorphism was not a susceptibility factor for ACS or DM2; however, the Ins/Ins genotype might have contributed to the development of HBP in the studied groups. PMID:24689061

Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and promoter methylation in cervical oncogenic lesions and cancer

PubMed Central

Botezatu, Anca; Socolov, Demetra; Iancu, Iulia V; Huica, Irina; Plesa, Adriana; Ungureanu, Carmen; Anton, Gabriela

2013-01-01

The aim of this study was to investigate the role of methylenetetrahydrofolate reductase (MTHFR) polymorphisms and MTHFR methylation pattern in cervical lesions development among women from Romania, a country with high prevalence of human papillomavirus (HPV) cervical infections. To achieve this goal, blood samples and cervical cytology specimens (n = 77)/tumour tissue specimens (n = 23) were investigated. As control, blood and negative cytological smears (n = 50) were used. A statistically significant association was found between T allele of C677T polymorphism and cervical lesions, heterozygote women presenting a threefold increased risk (normal/cervical lesions and tumours: wild homozygote 34/41 (0.68/0.41), heterozygote 14/51 (0.28/0.51), mutant homozygote 2/8 (0.04/0.08); OR = 3.081, P = 0.0035). Using χ square test for the control group, the HPV-negative and HPV-positive patients with cervix lesions, a significant correlation between viral infection and T allele of C677T polymorphism (P = 0.0287) was found. The MTHFR promoter was methylated in all HGSIL and tumour samples, significant differences being noted between HPV-positive samples, control group and cases of cervical dysplastic lesions without HPV DNA (P < 0. 0001) and between samples from patients with high-risk (hr)HPV versus low-risk (lr)HPV (P = 0.0026). No correlations between polymorphisms and methylation were observed. In Romania, individuals carrying T allele are susceptible for cervical lesions. MTHFR promoter methylation is associated with cervical severity lesions and with hrHPV. PMID:23444906

Polymorphism of matrix metalloproteinase genes (MMP1 and MMP3) in patients with varicose veins.

PubMed

Kurzawski, M; Modrzejewski, A; Pawlik, A; Droździk, M

2009-07-01

Several risk factors for varicose veins have been identified: female gender, combined with obesity and pregnancy, occupations requiring standing for long periods, sedentary lifestyle, history of deep-vein thrombosis and family history. However, no specific gene variants related to a wide prevalence of varicosities in general population have been identified. Extracellular matrix composition, predominantly maintained by matrix metalloproteinases (MMPs), may affect the vein-wall structure, which may lead to dilation of vessels and cause varicosities. MMP-1 (tissue collagenase I) and MMP-3 (stromelysin I) expression was found to be raised in varicose veins compared with normal vessels. Therefore, a study was conducted to evaluate a potential association between MMP1 and MMP3 promoter polymorphisms and a risk of varicose veins. Genotyping for the presence of the polymorphisms -1607dupG (rs1799750) in MMP1 and -1171dupA (rs3025058) in the MMP3 promoter region was performed using PCR and restriction-fragment length polymorphism assays in a group of 109 patients diagnosed with varicose veins and 112 healthy controls. The frequencies of the MMP1 and MMP3 alleles (minor allele frequency 0.440 in patients vs. 0.451 in the controls for MMP1-1607*G and 0.514 vs. 0.469 for MMP3-1171*dupA, respectively) and of genotypes did not differ significantly between patients and controls. The MMP1-1607dupG and MMP3-1171dupA promoter polymorphisms are not valuable markers of susceptibility for varicose veins.

Body adiposity but not insulin resistance is associated with -675 4G/5G polymorphism in the PAI-1 gene in a sample of Mexican children.

PubMed

de la Cruz-Mosso, Ulises; Muñoz-Valle, José Francisco; Salgado-Bernabé, Aralia Berenice; Castro-Alarcón, Natividad; Salgado-Goytia, Lorenzo; Sánchez-Corona, José; Flores-Martínez, Silvia Esperanza; Parra-Rojas, Isela

2013-01-01

To assess whether the -675 4G/5G polymorphism in the plasminogen activator inhibitor-1 gene is associated with obesity and insulin resistance in Mexican children. A cross-sectional study was performed in 174 children, 89 with normal-weight and 85 with obesity, aged from 6 to 13 years. All children were from state of Guerrero, and recruited from three primary schools in the city of Chilpancingo, state of Guerrero, Mexico. Insulin levels were determined by immunoenzymatic assay. The homeostasis model assessment was used to determine insulin resistance. The -675 4G/5G polymorphism in PAI-1 gene was analyzed by polymerase chain reaction-restriction fragment length polymorphism. The prevalence of insulin resistance in the obese group was higher (49.41%) than in the normal-weight group (16.85%). The 4G/5G PAI-1 polymorphism was found in Hardy Weinberg equilibrium. The 4G/5G genotype contributed to a significant increase in waist-hip ratio (β=0.02, p=0.006), waist circumference (β=4.42, p=0.009), and subscapular skinfold thickness (β=1.79, p=0.04); however, it was not related with insulin resistance. The -675 4G/5G genotype of PAI-1 gene was associated with increase of body adiposity in Mexican children. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Detection of an ABCA1 Variant Associated with Type 2 Diabetes Mellitus Susceptibility for Biochemistry and Genetic Laboratory Courses

ERIC Educational Resources Information Center

Legorreta-Herrera, M.; Mosqueda-Romo, N. A.; Hernández-Clemente, F.; Soto-Cruz, I.

2013-01-01

We selected diabetes mellitus for this laboratory exercise to provide students with an explicit model for scientific research concerning the association between the R230C polymorphism and susceptibility to type 2 diabetes mellitus, which is highly prevalent in the Mexican population. We used a collaborative project-based learning to engage…

Serotonergic genes and depressive disorder in acute coronary syndrome: The Korean depression in ACS (K-DEPACS) study.

PubMed

Kim, Jae-Min; Stewart, Robert; Kang, Hee-Ju; Bae, Kyung-Yeol; Kim, Sung-Wan; Shin, Il-Seon; Hong, Young Joon; Ahn, Youngkeun; Jeong, Myung Ho; Park, Sung-Woo; Kim, Young-Hoon; Yoon, Jin-Sang

2015-06-01

Genes coding for the serotonergic pathway have been associated with depressive disorders. However, these associations have rarely been tested in acute coronary syndrome (ACS) patients vulnerable to depression. This study aimed to investigate whether polymorphisms of serotonin transporter (5-HTT) and serotonin 2a receptor (5-HTR2a) genes are associated with occurrence of depressive disorder in ACS. 969 patients with recently developed ACS were recruited at baseline, and 711 were followed 1 year thereafter. Depressive disorder was diagnosed according to DSM-IV criteria, and analysed as an outcome at baseline (prevalence), and follow up (incidence and persistence). Genotypes were ascertained for 5-HTTLPR, STin2 VNTR, 5-HTR2a 102T/C, and 5-HTR2a 1438A/G. Logistic regression models were used to investigate associations. The 5-HTTLPR s/s genotype was independently associated with depressive disorder prevalence and persistence following ACS, but no significant associations were found with the other polymorphisms. ACS patients with the 5-HTTLPR s allele are thus potentially susceptible to depressive disorder in the early phase after ACS, and with its persistence over the subsequent year. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

PRKCSH genetic mutation was not found in Taiwanese patients with polycystic liver disease.

PubMed

Yang, An-Ming; Shih, Shou-Chuan; Chu, Cheng-Hsin; Wang, Tsang-En; Yang, Wei-Shiung

2010-03-01

Polycystic liver disease (PCLD) without polycystic kidney is infrequent in clinical setting. Family clustering is found in patients with PCLD, and it is inherited in an autosomal dominant fashion. Through positional cloning in North America and Europe (mostly in Dutch and Finnish descents), mutations in PRKCSH gene on chromosome 19 were found to be responsible for the disease. We investigated the prevalence of liver cysts and PCLD in Taiwan and investigated whether the PRKCSH mutations exist in Taiwanese. The prevalence of liver cysts is only 0.17% in people under 30 years old and increased gradually to 14.29% in people between 55 and 60 years old and 14.19% in people over 65 years old. PCLD was not found in people under 40 years old. The prevalence is 0.15% between 40 and 45 years old, and increased to 1.37% between 55 and 60 years old, 1.21% between 60 and 65 years old, and 0.99% over 65 years old. There is only one polymorphism (deletion of one GAG repeat in exon 11) found, and the genotype and allele frequency were the same in Taiwanese patients and controls. No mutation, even polymorphism reported in the literature, was found in the 20 cases of PCLD. Our results suggest that PRKCSH gene is not a major genetic cause of PCLD and there may be at least another locus responsible for the disease in Taiwan.

Can data science inform environmental justice and community risk screening for type 2 diabetes?

PubMed

Davis, J Allen; Burgoon, Lyle D

2015-01-01

Having the ability to scan the entire country for potential "hotspots" with increased risk of developing chronic diseases due to various environmental, demographic, and genetic susceptibility factors may inform risk management decisions and enable better environmental public health policies. Develop an approach for community-level risk screening focused on identifying potential genetic susceptibility hotpots. Our approach combines analyses of phenotype-genotype data, genetic prevalence of single nucleotide polymorphisms, and census/geographic information to estimate census tract-level population attributable risks among various ethnicities and total population for the state of California. We estimate that the rs13266634 single nucleotide polymorphism, a type 2 diabetes susceptibility genotype, has a genetic prevalence of 56.3%, 47.4% and 37.0% in Mexican Mestizo, Caucasian, and Asian populations. Looking at the top quintile for total population attributable risk, 16 California counties have greater than 25% of their population living in hotspots of genetic susceptibility for developing type 2 diabetes due to this single genotypic susceptibility factor. This study identified counties in California where large portions of the population may bear additional type 2 diabetes risk due to increased genetic prevalence of a susceptibility genotype. This type of screening can easily be extended to include information on environmental contaminants of interest and other related diseases, and potentially enables the rapid identification of potential environmental justice communities. Other potential uses of this approach include problem formulation in support of risk assessments, land use planning, and prioritization of site cleanup and remediation actions.

Geographically Distinct and Domain-Specific Sequence Variations in the Alleles of Rice Blast Resistance Gene Pib

PubMed Central

Vasudevan, Kumar; Vera Cruz, Casiana M.; Gruissem, Wilhelm; Bhullar, Navreet K.

2016-01-01

Rice blast is caused by Magnaporthe oryzae, which is the most destructive fungal pathogen affecting rice growing regions worldwide. The rice blast resistance gene Pib confers broad-spectrum resistance against Southeast Asian M. oryzae races. We investigated the allelic diversity of Pib in rice germplasm originating from 12 major rice growing countries. Twenty-five new Pib alleles were identified that have unique single nucleotide polymorphisms (SNPs), insertions and/or deletions, in addition to the polymorphic nucleotides that are shared between the different alleles. These partially or completely shared polymorphic nucleotides indicate frequent sequence exchange events between the Pib alleles. In some of the new Pib alleles, nucleotide diversity is high in the LRR domain, whereas, in others it is distributed among the NB-ARC and LRR domains. Most of the polymorphic amino acids in LRR and NB-ARC2 domains are predicted as solvent-exposed. Several of the alleles and the unique SNPs are country specific, suggesting a diversifying selection of alleles in various geographical locations in response to the locally prevalent M. oryzae population. Together, the new Pib alleles are an important genetic resource for rice blast resistance breeding programs and provide new information on rice-M. oryzae interactions at the molecular level. PMID:27446145

[Study of genetic variants in the BDNF, COMT, DAT1 and SERT genes in Colombian children with attention deficit disorder].

PubMed

Ortega-Rojas, Jenny; Arboleda-Bustos, Carlos E; Morales, Luis; Benítez, Bruno A; Beltrán, Diana; Izquierdo, Álvaro; Arboleda, Humberto; Vásquez, Rafael

Attention deficit and hyperactive disorder (ADHD) is highly prevalent among children in Bogota City. Both genetic and environmental factors play a very important role in the etiology of ADHD. However, to date few studies have addressed the association of genetic variants and ADHD in the Colombian population. To test the genetic association between polymorphisms in the DAT1, HTTLPR, COMT and BDNF genes and ADHD in a sample from Bogota City. We genotyped the most common polymorphisms in DAT1, SERT, COMT and BDNF genes associated with ADHD using conventional PCR followed by restriction fragment length polymorphism (RFLP) in 97 trios recruited in a medical center in Bogota. The transmission disequilibrium test (TDT) was used to determine the association between such genetic variants and ADHD. The TDT analysis showed that no individual allele of any variant studied has a preferential transmission. Our results suggest that the etiology of the ADHD may be complex and involves several genetic factors. Further studies in other candidate polymorphisms in a larger sample size will improve our knowledge of the ADHD in Colombian population. Copyright © 2016 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Molecular epidemiology of HFE gene polymorphic variants (C282Y, H63D and S65C) in the population of Espírito Santo, Brazil.

PubMed

Alves, L N R; Santos, E V W; Stur, E; Silva Conforti, A M A; Louro, I D

2016-04-27

Hereditary hemochromatosis (HH) is an autosomal recessive disorder that leads to progressive iron accumulation and may cause cirrhosis, hepatocellular carcinoma, diabetes, and heart failure. Most cases of HH have been linked to mutations in genes associated with iron homeostasis. There have been three major variants in the high Fe (HFE) gene associated with the disease: C282Y, H63D and S65C. In this context, we aimed to evaluate the prevalence of the polymorphic variants (C282Y, H63D and S65C) of the HFE gene in the population of the Espírito Santo State (ES), Brazil by analyzing three different groups: general population (N = 120), Pomeranian descendants (N = 59), and patients with HH (N = 20). Using genomic DNA extracted from peripheral blood, polymorphic variant identification was performed by polymerase chain reaction-restriction fragment length polymorphism. Statistically significant differences were observed for genotype distribution of C282Y (P < 0.001) and H63D (P = 0.013) between the general population and the patients diagnosed with HH. This is the first study to analyze HFE gene allele frequencies for the general population, Pomeranian subpopulation, and patients with HH of ES, Brazil.

Beta 2 adrenergic receptor polymorphisms, at codons 16 and 27, and bronchodilator responses in adult Venezuelan asthmatic patients.

PubMed

Larocca, Nancy; Moreno, Dolores; Garmendia, Jenny Valentina; Velasquez, Olga; Martin-Rojo, Joana; Talamo, Carlos; Garcia, Alexis; De Sanctis, Juan Bautista

2013-12-01

One of the gene polymorphisms often studied in asthmatic patients is the β2 adrenergic receptor (ADRβ2). Even though in the Venezuelan Mestizo population there is a high incidence of asthma, there are no direct reports of ADRβ2 gene polymorphism, and treatment response. The aim of this study was to assess, in this population, the gene frequency of ADRβ2 polymorphisms at codons 16 Arg/Gly and 27 Gln/Glu, allergen sensitization, and its relationship to bronchodilator response. Purified genomic DNA was obtained form 105 Mestizo asthmatic and 100 Mestizo healthy individuals from Venezuela. The two polymorphisms were assessed by PCR-RFLP. Patient sensitization to aeroallergens and their response to bronchodilatation were correlated. Significant differences between patients and controls were recorded in: 1) the prevalence of Arg/Arg at codon 16 (28.6% in patients vs. 47% in controls, P<0.01), 2) the frequency of heterozygotes Arg/Gly (55% in patients vs. 35% in controls, P<0.01). Conversely, no differences in polymorphism frequencies were found at codon 27. The haplotypes Arg/Gly-Gln/Gln were more common in patients than controls (P <0.01), whereas the Arg/Arg-Gln/Glu combination prevailed in the control group (P<0.01). The Arg/Gly and Gln/Glu genotypes were associated with better responses after salbutamol. The asthmatic homozygotes Arg/Arg have higher sensitivity to aeroallergens. The difference in Arg/Arg frequency between groups suggests that this could be a protective genotype although the asthmatic group had a higher sensitivity to aeroallergens. The asthmatic heterozygotes had better bronchodilator responses than the homozygotes.

Association between MTHFR C677T polymorphism and depression: a meta-analysis in the Chinese population.

PubMed

Jiang, Wei; Xu, Jun; Lu, Xiao-Jie; Sun, Yang

2016-09-01

Depression is a worldwide public health issue, and its prevalence increases each year. Although a number of studies have been conducted on the association between MTHFR C677T polymorphism and depression in China, this association remains elusive and controversial. To clarify the impact of MTHFR C677T polymorphism on the risk of depression, a meta-analysis was performed in the Chinese population. Relevant studies were identified using PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure and Chinese Biology Medicine through May 5, 2015. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. A total of 13 case-control studies including 1895 patients and 1913 controls were involved in this meta-analysis. Overall, T variant of MTHFR C677T gene polymorphism was significantly associated with an increased risk of depression in the Chinese population (T vs. C: OR = 1.52, 95% CI = 1.24-1.85; TT + CT vs. CC: OR = 1.64, 95% CI = 1.16-2.30; TT vs. CC: OR = 2.19, 95% CI = 1.49-3.24; TT vs. CC + CT: OR = 1.80, 95% CI = 1.31-2.46). In subgroup analyses stratified by geographic area and source of controls, the significant results were found in population-based studies, in hospital-based studies, in North and South China. The risk conferred by MTHFR C677T polymorphism is higher in North China than in South China. In conclusion, this meta-analysis suggests that MTHFR C677T polymorphism is associated with depression in the Chinese population, but these associations vary in different geographic locations.

Association of the Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma2 with decreased basic metabolic rate in women with polycystic ovary syndrome.

PubMed

Koika, Vasiliki; Marioli, Dimitra J; Saltamavros, Alexandros D; Vervita, Vasiliki; Koufogiannis, Kleanthis D; Adonakis, George; Decavalas, George; Georgopoulos, Neoklis A

2009-08-01

The peroxisome proliferator-activated receptor (PPAR)gamma is a transcription factor involved in glucose homeostasis and energy metabolism. A missense mutation at codon 12 in the PPARgamma2 has been associated with increased body mass index (BMI) and attenuated insulin resistance (IR) in polycystic ovary syndrome (PCOS). We have recently shown a decreased basic metabolic rate (BMR) in PCOS. The aim of the present study is to determine the prevalence of the Pro12Ala polymorphism of the PPARgamma2 gene and its associations with indices of IR and BMR in lean and slightly overweight PCOS women. Case-control association study involving 156 PCOS women with biochemical hyperandrogenism, chronic anovulation and polycystic ovarian morphology in ultrasound and 56 unrelated healthy controls. Hormonal determinations were performed by electrochemiluminescence quantitation or RIA. BMR was measured by indirect calorimetry. All subjects were genotyped by a PCR-restriction fragment length polymorphism assay. Genotype frequencies of the Pro12Ala polymorphism in PPARgamma2 did not differ among PCOS women and control subjects. The presence of Pro12Ala polymorphism of PPARgamma2 was associated with lower BMR (P=0.04). This finding was valid in our subgroup of lean PCOS (BMI<25 kg/m(2)), in which the Ala variant was also associated with higher total testosterone values. The Pro12Ala polymorphism in the PPARgamma2 gene is associated with decreased BMR in women with PCOS and biochemical hyperandrogenemia. These young women are therefore at risk to increase their body weight and should restrict their energy intake by diet and enhance their energy expenditure by exercise.

Computational Analysis of Single Nucleotide Polymorphisms Associated with Altered Drug Responsiveness in Type 2 Diabetes

PubMed Central

Costa, Valerio; Federico, Antonio; Pollastro, Carla; Ziviello, Carmela; Cataldi, Simona; Formisano, Pietro; Ciccodicola, Alfredo

2016-01-01

Type 2 diabetes (T2D) is one of the most frequent mortality causes in western countries, with rapidly increasing prevalence. Anti-diabetic drugs are the first therapeutic approach, although many patients develop drug resistance. Most drug responsiveness variability can be explained by genetic causes. Inter-individual variability is principally due to single nucleotide polymorphisms, and differential drug responsiveness has been correlated to alteration in genes involved in drug metabolism (CYP2C9) or insulin signaling (IRS1, ABCC8, KCNJ11 and PPARG). However, most genome-wide association studies did not provide clues about the contribution of DNA variations to impaired drug responsiveness. Thus, characterizing T2D drug responsiveness variants is needed to guide clinicians toward tailored therapeutic approaches. Here, we extensively investigated polymorphisms associated with altered drug response in T2D, predicting their effects in silico. Combining different computational approaches, we focused on the expression pattern of genes correlated to drug resistance and inferred evolutionary conservation of polymorphic residues, computationally predicting the biochemical properties of polymorphic proteins. Using RNA-Sequencing followed by targeted validation, we identified and experimentally confirmed that two nucleotide variations in the CAPN10 gene—currently annotated as intronic—fall within two new transcripts in this locus. Additionally, we found that a Single Nucleotide Polymorphism (SNP), currently reported as intergenic, maps to the intron of a new transcript, harboring CAPN10 and GPR35 genes, which undergoes non-sense mediated decay. Finally, we analyzed variants that fall into non-coding regulatory regions of yet underestimated functional significance, predicting that some of them can potentially affect gene expression and/or post-transcriptional regulation of mRNAs affecting the splicing. PMID:27347941

The AVPR1A Gene and Its Single Nucleotide Polymorphism rs10877969: A Literature Review of Associations with Health Conditions and Pain.

PubMed

Roach, Keesha L; Hershberger, Patricia E; Rutherford, Julienne N; Molokie, Robert E; Wang, Zaijie Jim; Wilkie, Diana J

2018-03-01

Pain is the quintessential symptom for individuals suffering from sickle cell disease (SCD). Although the degree of suffering and the cost of treatment are staggering, SCD continues to be grossly understudied, including a lack of data for pain-related genes and prevalence of polymorphisms in this population. This lack of data adds to the inadequacy of pain therapy in this population. Pain genetics investigators have recently examined allele frequencies of single-nucleotide polymorphisms from candidate genes in people who have SCD. One of the genes identified was the arginine vasopressin receptor 1A gene (AVPR1A) and its associated single-nucleotide polymorphism (SNP) rs10877969. Progress in explaining pain-related polymorphisms associated with SCD can be facilitated by understanding the literature. The purpose of this literature review was to describe mechanisms of the polymorphic gene AVPR1A and the phenotypic variations associated with its SNPs relative to health conditions and pain. Published studies were included if the research addressed AVPR1A and was a full article in a peer-reviewed journal, in the English language, a human or animal study, and published 2009 to present. Abstracts were included if they were in English and provided information not found in a full article. The results of this review revealed that AVPR1A is associated with behavioral phenotypes, which include pair bonding, autism spectrum disorder, musical aptitude, infidelity, altruism, monogamy, mating, substance abuse, and alcohol preference. In addition, there were associations with pain, stress pain by sex, and sickle cell pain. Summary of this literature could provide insights into future pain research of this SNP in people with SCD. Copyright © 2018 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Association between ghrelin gene (Leu72Met) polymorphism and ghrelin serum level with coronary artery diseases.

PubMed

Hedayatizadeh-Omran, Akbar; Rafiei, Alireza; Khajavi, Rezvan; Alizadeh-Navaei, Reza; Mokhberi, Vahid; Moradzadeh, Kambiz

2014-02-01

Research shows that ghrelin gene polymorphism has some association with coronary artery diseases (CAD). Due to genetic differences among nations and the high prevalence of CAD, we conducted this study to examine the possible association between the polymorphism of ghrelin gene Leu72Met and CAD among an Iranian population. This case-control study was undertaken with patients who were referred to referral heart center, in 2011, with chest pain or a positive exercise test. Patients with risk factors for heart disease or who were surgery candidates, who underwent angiography and echocardiography, were also included. DNA extractions were performed using a modified salting out method, and the ghrelin region was amplified using polymerase chain reaction. The presence of the Leu72Met polymorphism and the serum levels of ghrelin were determined using the restriction fragment length polymorphism method and the enzyme-linked immunosorbent assay, respectively. The results indicated that in CAD patients, the incidence of heart failure was significantly different between the groups with genotypes CC or AA+CA (p=0.041). Mean serum level of ghrelin in the CAD group was significantly higher than that in the control group (p<0.0001). Additionally, there was a significant relationship between the distribution of ghrelin genotypes and serum levels of ghrelin in both the CAD and control groups (p<0.0001). This study indicates that there was a significant association between heart failure in CAD patients and the presence of the polymorphism, as well as an increase in serum levels of ghrelin associated with genotype distribution such that ghrelin levels have an inverse relationship with the frequency of the CC genotype.

Clinical differences between patients with MODY-3, MODY-2 and type 2 diabetes mellitus with I27L polymorphism in the HNF1alpha gene.

PubMed

Pinés Corrales, Pedro José; López Garrido, María P; Aznar Rodríguez, Silvia; Louhibi Rubio, Lynda; López Jiménez, Luz M; Lamas Oliveira, Cristina; Alfaro Martínez, Jose J; Lozano García, Jose J; Hernández López, Antonio; Requejo Castillo, Ramón; Escribano Martínez, Julio; Botella Romero, Francisco

2010-01-01

The aim of our study was to describe and evaluate the clinical and metabolic characteristics of patients with MODY-3, MODY-2 or type 2 diabetes who presented I27L polymorphism in the HNF1alpha gene. The study included 31 previously diagnosed subjects under follow-up for MODY-3 (10 subjects from 5 families), MODY-2 (15 subjects from 9 families), or type 2 diabetes (6 subjects) with I27L polymorphism in the HNF1alpha gene. The demographic, clinical, metabolic, and genetic characteristics of all patients were analyzed. No differences were observed in distribution according to sex, age of onset, or form of diagnosis. All patients with MODY-2 or MODY-3 had a family history of diabetes. In contrast, 33.3% of patients with type 2 diabetes mellitus and I27L polymorphism in the HNF1alpha gene had no family history of diabetes (p < 0.05). No differences were observed in body mass index, prevalence of hypertension, or microvascular or macrovascular complications. Drug therapy was required by 100% of MODY-3 patients, but not required by 100% of MODY-2 patients or 16.7% of patients with type 2 diabetes mellitus and I27L polymorphism in the HNF1alpha gene (p < 0.05). Occasional difficulties may be encountered when classifying patients with MODY-2, MODY-3 or type 2 diabetes of atypical characteristics, in this case patients who present I27L polymorphism in the HNF1alpha gene. Copyright 2010 Sociedad Española de Endocrinología y Nutrición. Published by Elsevier Espana. All rights reserved.

Polymorphism of the ACE gene and the risk of obstructive sleep apnoea.

PubMed

Chmielewska, Izabela; Mlak, Radosław; Krawczyk, Paweł; Czukiewska, Ewa; Milanowski, Janusz

2013-01-01

Obstructive sleep apnoea/hypopnea syndrome (OSA) is characterized by obstruction of the upper airway during sleep, resulting in repetitive breathing pauses accompanied by oxygen desaturation and arousal from sleep. Among the candidate genes affecting the risk of OSA, genes whose polymorphisms influence the development of diseases with similar pathogenesis such as OSA could be listed: APOE, genes for leptin and leptin receptor, TNFA1, ADRB2 and ACE (gene for angiotensin-converting enzyme). Until now there has been a confirmed relationship between ACE gene polymorphism and cardiovascular diseases, but its effect on the incidence of OSA is debatable. The aim of this study was to investigate the effect of ACE gene insertion/deletion (I/D) polymorphism on the risk of OSA. Fifty-five patients with confirmed diagnose of OSA and qualified to CPAP therapy entered the study. The control group included 50 subjects who did not complain of any sleep related symptoms. Diagnose of OSA was set on the basis of full overnight polysomnography together with Epworth Sleepiness Scale according to American Academy of Sleep Medicine guidelines. DNA was isolated from peripheral blood leukocytes with Qiagen DNA mini Kit. ACE gene polymorphism was determined in genomic DNA using allele specific polymerase chain reaction. Different sizes of PCR products were observed on agarose gel electrophoresis. There were non-significant differences in the frequency of ACE genotypes. However, allele D had significantly lower prevalence in the study group than in the control group. (χ(2) = 4.25 p = 0.04). Moreover, I allele carriers had a threefold greater risk of developing OSA (HR = 2.748, 95% CI = 1.029-7.340, p < 0.05). Analysis of ACE gene polymorphism might be useful to determine the risk of developing OSA in clinically predisposed patients.

Polymorphism in the PER3 promoter associates with diurnal preference and delayed sleep phase disorder.

PubMed

Archer, Simon N; Carpen, Jayshan D; Gibson, Mark; Lim, Gim Hui; Johnston, Jonathan D; Skene, Debra J; von Schantz, Malcolm

2010-05-01

To screen the PER3 promoter for polymorphisms and investigate the phenotypic associations of these polymorphisms with diurnal preference, delayed sleep phase disorder/syndrome (DSPD/DSPS), and their effects on reporter gene expression. Interspecific comparison was used to define the approximate extent of the PER3 promoter as the region between the transcriptional start site and nucleotide position -874. This region was screened in DNA pools using PCR and direct sequencing, which was also used to screen DNA from individual participants. The different promoter alleles were cloned into a luciferase expression vector and a deletion library created. Promoter activation was measured by chemiluminescence. N/A. DNA samples were obtained from volunteers with defined diurnal preference (3 x 80, selected from a pool of 1,590), and DSPD patients (n=23). N/A. We verified three single nucleotide polymorphisms (G -320T, C -319A, G -294A), and found a novel variable number tandem repeat (VNTR) polymorphism (-318 1/2 VNTR). The -320T and -319A alleles occurred more frequently in DSPD compared to morning (P = 0.042 for each) or evening types (P = 0.006 and 0.033). The allele combination TA2G was more prevalent in DSPD compared to morning (P 0.033) or evening types (P = 0.002). Luciferase expression driven by the TA2G combination was greater than for the more common GC2A (P < 0.05) and the rarer TA1G (P < 0.001) combinations. Deletion reporter constructs identified two enhancer regions (-703 to -605, and -283 to -80). Polymorphisms in the PER3 promoter could affect its expression, leading to potential differences in the observed functions of PER3.

Promoter Polymorphisms in the Nitric Oxide Synthase 3 Gene Are Associated With Ischemic Stroke Susceptibility in Young Black Women

PubMed Central

Howard, Timothy D.; Giles, Wayne H.; Xu, Jianfeng; Wozniak, Marcella A.; Malarcher, Ann M.; Lange, Leslie A.; Macko, Richard F.; Basehore, Monica J.; Meyers, Deborah A.; Cole, John W.; Kittner, Steven J.

2006-01-01

Background and Purpose Endothelial nitric oxide exerts a variety of protective effects on endothelial cells and blood vessels, and therefore the nitric oxide synthase 3 gene (NOS3) is a logical candidate gene for stroke susceptibility. Methods We used the population-based Stroke Prevention in Young Women case-control study to assess the association of five NOS3 polymorphisms in 110 cases (46% black) with ischemic stroke and 206 controls (38% black), 15 to 44 years of age. Polymorphisms included 3 single nucleotide polymorphisms (SNPs) in the promoter region (−1468 T>A, −922 G>A, −786 T>C), 1 SNP in exon 7 (G894T), and 1 insertion/deletion polymorphism within intron 4. Results Significant associations with both the −922 G>A and −786 T>C SNPs with ischemic stroke were observed in the black, but not the white, population. This association was attributable to an increased prevalence of the −922 A allele (OR=3.0, 95% CI=1.3 to 6.8; P=0.005) and the −786 T allele (OR=2.9, 95% CI=1.3 to 6.4; P=0.005) in cases versus controls. These 2 SNPs were in strong linkage disequilibrium (D′=1.0), making it impossible to determine, within the confines of this genetic study, whether 1 or both of these polymorphisms are functionally related to NOS3 expression. Two sets of haplotypes were also identified, 1 of which may confer an increased susceptibility to stroke in blacks, whereas the other appears to be protective. Conclusion Promoter variants in NOS3 may be associated with ischemic stroke susceptibility among young black women. PMID:16100023

Promoter polymorphisms in the nitric oxide synthase 3 gene are associated with ischemic stroke susceptibility in young black women.

PubMed

Howard, Timothy D; Giles, Wayne H; Xu, Jianfeng; Wozniak, Marcella A; Malarcher, Ann M; Lange, Leslie A; Macko, Richard F; Basehore, Monica J; Meyers, Deborah A; Cole, John W; Kittner, Steven J

2005-09-01

Endothelial nitric oxide exerts a variety of protective effects on endothelial cells and blood vessels, and therefore the nitric oxide synthase 3 gene (NOS3) is a logical candidate gene for stroke susceptibility. We used the population-based Stroke Prevention in Young Women case-control study to assess the association of five NOS3 polymorphisms in 110 cases (46% black) with ischemic stroke and 206 controls (38% black), 15 to 44 years of age. Polymorphisms included 3 single nucleotide polymorphisms (SNPs) in the promoter region (-1468 T>A, -922 G>A, -786 T>C), 1 SNP in exon 7 (G894T), and 1 insertion/deletion polymorphism within intron 4. Significant associations with both the -922 G>A and -786 T>C SNPs with ischemic stroke were observed in the black, but not the white, population. This association was attributable to an increased prevalence of the -922 A allele (OR=3.0, 95% CI=1.3 to 6.8; P=0.005) and the -786 T allele (OR=2.9, 95% CI=1.3 to 6.4; P=0.005) in cases versus controls. These 2 SNPs were in strong linkage disequilibrium (D'=1.0), making it impossible to determine, within the confines of this genetic study, whether 1 or both of these polymorphisms are functionally related to NOS3 expression. Two sets of haplotypes were also identified, 1 of which may confer an increased susceptibility to stroke in blacks, whereas the other appears to be protective. Promoter variants in NOS3 may be associated with ischemic stroke susceptibility among young black women.

Characteristics of clinical Helicobacter pylori strains from Ecuador.

PubMed

Debets-Ossenkopp, Yvette J; Reyes, Germán; Mulder, Janet; aan de Stegge, Birgit M; Peters, José T A M; Savelkoul, Paul H M; Tanca, J; Peña, Amado S; Vandenbroucke-Grauls, Christina M J E

2003-01-01

In Ecuador, Helicobacter pylori infections are highly prevalent. A total of 42 H. pylori clinical isolates from 86 patients attending the outpatient clinic of the gastroenterology department of the university hospital of Guayaquil in Ecuador were characterized. Their susceptibility, and cagA and vacA status were determined. Resistance to metronidazole and clarithromycin was found in 80.9% and 9.5% of strains, respectively. Neither amoxicillin- nor tetracycline-resistant strains were found. The most prevalent genotype was the cagA(+), vacA s1b,m1 type. This genotype was associated with gastric cancer and peptic ulcer. Typing by random amplified polymorphic DNA showed no genetic relationship among the strains.

Association between the -455T>C promoter polymorphism of the APOC3 gene and the metabolic syndrome in a multi-ethnic sample.

PubMed

Pollex, Rebecca L; Ban, Matthew R; Young, T Kue; Bjerregaard, Peter; Anand, Sonia S; Yusuf, Salim; Zinman, Bernard; Harris, Stewart B; Hanley, Anthony J G; Connelly, Philip W; Huff, Murray W; Hegele, Robert A

2007-12-20

Common polymorphisms in the promoter of the APOC3 gene have been associated with hypertriglyceridemia and may impact on phenotypic expression of the metabolic syndrome (MetS). The rs7566605 marker, located near the INSIG2 gene, has been found to be associated with obesity, making it also a potential genetic determinant for MetS. The objective of this study is to examine the APOC3 -455T>C and the INSIG2 rs7566605 polymorphisms as potential genetic determinants for MetS in a multi-ethnic sample. Subjects were genotyped for both the APOC3 -455T>C and INSIG2 rs7566605 polymorphisms, and classified for the presence or absence of MetS (NCEP ATP III and IDF definitions). The total study population included 2675 subjects (> or =18 years of age) from six different geographical ancestries. For the overall study population, the prevalence of MetS was 22.6% (NCEP ATP III definition). Carriers of > or =1 copy of APOC3 -455C were more likely to have MetS (NCEP ATP III definition) than noncarriers (carrier odds ratio 1.73, 95% CI 1.40 to 2.14, adjusting for age and study group). The basis of the association was related not only to a higher proportion of -455C carriers meeting the triglyceride and high-density lipoprotein cholesterol criteria, but also the blood pressure criteria compared with wild-type homozygotes. Plasma apo C-III concentrations were not associated with APOC3 -455T>C genotype. The INSIG2 rs7566605 polymorphism was not associated with MetS or measures of obesity. Meta-analysis of the sample of multiple geographic ancestries indicated that the functional -455T>C promoter polymorphism in APOC3 was associated with an approximately 2-fold increased risk of MetS, whereas the INSIG2 rs7566605 polymorphism was not associated with MetS.

Association between the -455T>C promoter polymorphism of the APOC3 gene and the metabolic syndrome in a multi-ethnic sample

PubMed Central

Pollex, Rebecca L; Ban, Matthew R; Young, T Kue; Bjerregaard, Peter; Anand, Sonia S; Yusuf, Salim; Zinman, Bernard; Harris, Stewart B; Hanley, Anthony JG; Connelly, Philip W; Huff, Murray W; Hegele, Robert A

2007-01-01

Background Common polymorphisms in the promoter of the APOC3 gene have been associated with hypertriglyceridemia and may impact on phenotypic expression of the metabolic syndrome (MetS). The rs7566605 marker, located near the INSIG2 gene, has been found to be associated with obesity, making it also a potential genetic determinant for MetS. The objective of this study is to examine the APOC3 -455T>C and the INSIG2 rs7566605 polymorphisms as potential genetic determinants for MetS in a multi-ethnic sample. Methods Subjects were genotyped for both the APOC3 -455T>C and INSIG2 rs7566605 polymorphisms, and classified for the presence or absence of MetS (NCEP ATP III and IDF definitions). The total study population included 2675 subjects (≥18 years of age) from six different geographical ancestries. Results For the overall study population, the prevalence of MetS was 22.6% (NCEP ATP III definition). Carriers of ≥1 copy of APOC3 -455C were more likely to have MetS (NCEP ATP III definition) than noncarriers (carrier odds ratio 1.73, 95% CI 1.40 to 2.14, adjusting for age and study group). The basis of the association was related not only to a higher proportion of -455C carriers meeting the triglyceride and high-density lipoprotein cholesterol criteria, but also the blood pressure criteria compared with wild-type homozygotes. Plasma apo C-III concentrations were not associated with APOC3 -455T>C genotype. The INSIG2 rs7566605 polymorphism was not associated with MetS or measures of obesity. Conclusion Meta-analysis of the sample of multiple geographic ancestries indicated that the functional -455T>C promoter polymorphism in APOC3 was associated with an approximately 2-fold increased risk of MetS, whereas the INSIG2 rs7566605 polymorphism was not associated with MetS. PMID:18096054

Variation in human genetic polymorphisms, their association with Helicobacter pylori acquisition and gastric cancer in a multi-ethnic country.

PubMed

Schmidt, Heather-Marie A; Ha, Dung Mai; Taylor, Elizabeth F; Kovach, Zsuzsanna; Goh, Khean-Lee; Fock, Kwong Ming; Barrett, Jennifer H; Forman, David; Mitchell, Hazel

2011-12-01

The contribution of human genetic polymorphisms to Helicobacter pylori infection and gastric cancer (GC) development remains unclear due to geographic variation in the association between specific host genetic polymorphisms and GC. In the current study we investigated the association between polymorphisms related to immune and cancer-related pathways and H. pylori infection among the major ethnicities, Chinese, Malay and Indian, resident in Singapore and Malaysia as well as the association between these polymorphisms and GC development in ethnic Chinese patients. Thirty-four polymorphisms in 26 genes were typed by mass spectrometry in 422 patients undergoing endoscopy (162 Chinese, 113 Indian and 87 Malay controls and 60 Chinese GC cases). Patients were assessed for evidence of H. pylori infection. Odds ratios (OR) and confidence intervals (CI) were obtained using logistic regression models. The prevalence of 16 polymorphisms varied significantly among the ethnicities. In the Chinese subgroup, nominally significant associations were shown between (i) EBBR2+1963G (rs1801200) and H. pylori infection (per-allele OR: 0.48, 95% CI 0.23, 0.98, P = 0.04), (ii) PTGS2-1195G (rs689466) and an increased risk of GC on adjusting for H. pylori status (OR: 1.53, 95% CI 0.99, 2.37, P = 0.05), and (iii) IL1B-1473C (rs1143623) and a decreased risk of GC (OR: 0.64, 95% CI 0.41, 0.99, P = 0.05). Borderline significant associations were seen between IL2-330G (rs2069762) (OR 1.45, 95% CI 0.95, 2.15, P = 0.06) and IL13-1111T (rs1800925) (OR 0.65, 95% CI 0.42, 1.01, P = 0.06) and H. pylori infection. These findings contribute to the understanding of the genetic variation between ethnicities, which may influence H. pylori susceptibility and the outcome of infection. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Evaluation of Effect CAT -262C/T, SOD + 35A/C, GPx1 Pro197Leu Polymorphisms in Patients with IBD in the Polish Population.

PubMed

Mrowicki, Jerzy; Mrowicka, Małgorzata; Majsterek, Ireneusz; Mik, Michał; Dziki, Adam; Dziki, Łukasz

2016-12-01

Inflammatory bowel disease (IBD) are a heterogeneous group of disorders in the course dominated by chronic, recurrent gastrointestinal inflammation. It is believed that the activation of IBD occurs in patients with a genetic predisposition to their development. Chronic inflammation develops as a result of an excessive reaction of the immune system principally under the influence of environmental risk factors. Among them, it has been shown that the mechanism of oxidative stress is associated with the pathophysiology of inflammatory bowel disease, responsible for the commencement and progress of these diseases. The aim of the study was the relationship between single nucleotide polymorphisms (SNPs) of individual antioxidant enzymes, and the prevalence of inflammatory bowel disease that may be associated with increased levels of oxidative stress. A total of 111 IBD patients, including 65 patients with ulcerative colitis (UC) and 46 with Crohn's disease (CD) and 125 healthy controls recruited from the Polish population, were genotyped for CAT -262C / T (rs1001179), SOD + 35A / C (rs2234694), GPx Pro 197 Leu polymorphisms. Genotyping of CAT, SOD, GPx gene polymorphism was performed by a RFLP-PCR. The performed analysis of genetic polymorphisms of antioxidant enzymes showed that polymorphic variant of the CAT -262 C / T may have protective effects in patients with ulcerative colitis in the range of genotype C / T; OR = 0.49 (0.25-0.99), p = 0.044. Trend protective, but statistically unrelated, it was also observed for genotype T / T and T allele of the same polymorphism and genotypes and alleles + 35A / C SOD1 in UC as well as polymorphic variants CAT -262 C / T, Pro197Leu of GPx1, + 35A / C SOD1 in CD. The results were compared with a control group of potentially healthy individuals without such diseases. It has been shown that the polymorphism of antioxidant enzymes CAT gene -262 C / T may have protective effects in patients who are carriers of a genotype C / T at the UC. The potential protective effect without statistical relationships were also observed for other genotypes and alleles studied polymorphic variants of antioxidant enzymes in CD and CAT- 262C / T and + 35 A / C SOD1 in UC. Conducted our audit should be extended to more group of patients in order to assess whether or not to confirm the observed during analysis, the protective effect of CAT-262 C / T in ulcerative colitis and other trends observed for other polymorphic variants tested genes.

Long interspersed repeated DNA (LINE) causes polymorphism at the rat insulin 1 locus.

PubMed

Lakshmikumaran, M S; D'Ambrosio, E; Laimins, L A; Lin, D T; Furano, A V

1985-09-01

The insulin 1, but not the insulin 2, locus is polymorphic (i.e., exhibits allelic variation) in rats. Restriction enzyme analysis and hybridization studies showed that the polymorphic region is 2.2 kilobases upstream of the insulin 1 coding region and is due to the presence or absence of an approximately 2.7-kilobase repeated DNA element. DNA sequence determination showed that this DNA element is a member of a long interspersed repeated DNA family (LINE) that is highly repeated (greater than 50,000 copies) and highly transcribed in the rat. Although the presence or absence of LINE sequences at the insulin 1 locus occurs in both the homozygous and heterozygous states, LINE-containing insulin 1 alleles are more prevalent in the rat population than are alleles without LINEs. Restriction enzyme analysis of the LINE-containing alleles indicated that at least two versions of the LINE sequence may be present at the insulin 1 locus in different rats. Either repeated transposition of LINE sequences or gene conversion between the resident insulin 1 LINE and other sequences in the genome are possible explanations for this.

CCR5 polymorphism and plague resistance in natural populations of the black rat in Madagascar.

PubMed

Tollenaere, C; Rahalison, L; Ranjalahy, M; Rahelinirina, S; Duplantier, J-M; Brouat, C

2008-12-01

Madagascar remains one of the world's largest plague foci. The black rat, Rattus rattus, is the main reservoir of plague in rural areas. This species is highly susceptible to plague in plague-free areas (low-altitude regions), whereas rats from the plague focus areas (central highlands) have evolved a disease-resistance polymorphism. We used the candidate gene CCR5 to investigate the genetic basis of plague resistance in R. rattus. We found a unique non-synonymous substitution (H184R) in a functionally important region of the gene. We then compared (i) CCR5 genotypes of dying and surviving plague-challenged rats and (ii) CCR5 allelic frequencies in plague focus and plague-free populations. Our results suggested a higher prevalence of the substitution in resistant animals compared to susceptible individuals, and a tendency for higher frequencies in plague focus areas compared to plague-free areas. Therefore, the CCR5 polymorphism may be involved in Malagasy black rat plague resistance. CCR5 and other undetermined plague resistance markers may provide useful biological information about host evolution and disease dynamics.

Associations between polymorphisms of HLA-B gene and postmenopausal osteoporosis in Chinese Han population.

PubMed

Li, S-M; Zhou, D-X; Liu, M-Y

2014-08-01

Osteoporosis is a systemic skeletal disease, which is more prevalent in postmenopausal women. Osteoporosis likely develops beginning with genetic risk. This study explored the relationships between polymorphisms of HLA-B gene and postmenopausal osteoporosis in a Chinese Han population. Polymerase chain reaction sequence-based typing (PCR-SBT) method was used for DNA typing at HLA-B locus in 70 patients with postmenopausal osteoporosis and 73 healthy controls in female Han population of Shaanxi Province, situated in north-western China. We found that 40 HLA-B alleles in postmenopausal osteoporosis patients and control subjects, respectively. Furthermore, the frequency of HLA-B* 3501 allele was significantly higher in postmenopausal osteoporosis patients than in the control group (P = 0.033), and the relative risk was 7.632 (95% CI: 0.927-62.850). Our results suggest that HLA-B* 3501 was likely an important risk factor for postmenopausal osteoporosis. As different populations have different HLA polymorphisms, further investigation of the relationship of various HLA genes and osteoporosis with larger sample size is still necessary in the future. © 2014 John Wiley & Sons Ltd.

Novel approach of molecular genetic understanding of iridology: relationship between iris constitution and angiotensin converting enzyme gene polymorphism.

PubMed

Um, Jae-Young; An, Nyeon-Hyoung; Yang, Gui-Bi; Lee, Geon-Mok; Cho, Ju-Jang; Cho, Jae-Woon; Hwang, Woo-Jun; Chae, Han-Jung; Kim, Hyung-Ryong; Hong, Seung-Heon; Kim, Hyung-Min

2005-01-01

Iridology is the study of the iris of the eye to detect the conditions of the body and its organs, genetic strengths and weaknesses, etc. Although iridology is not widely used as a scientific tool for healthcare professionals to get to the source of people's health conditions, it has been used as a supplementary source to help the diagnosis of medical conditions by noting irregularities of the pigmentation in the iris among some Korean Oriental medical doctors. Angiotensin converting enzyme (ACE) gene polymorphism is one of the most well studied genetic markers of vascular disease. We investigated the relationship between iridological constitution and ACE polymorphism in hypertensives. We classified 87 hypertensives and 79 controls according to iris constitution and determined the ACE genotype of each individual. DD genotype was more prevalent in patients with a neurogenic constitution than in controls. This finding supports the hypothesis that D allele is a candidate gene for hypertension and demonstrates the association among ACE genotype, Korean hypertensives and iris constitution.

Three major glucose-6-phosphate dehydrogenase-deficient polymorphic variants identified in Mazandaran state of Iran.

PubMed

Mesbah-Namin, Seyed A; Sanati, Mohammad H; Mowjoodi, Alireza; Mason, Philip J; Vulliamy, Tom J; Noori-Daloii, Mohammad R

2002-06-01

We report the first investigation of glucose- 6-phosphate dehydrogenase (G6PD) deficiency among the Mazandaranians in the north of Iran. We analysed the G6PD gene in 74 unrelated G6PD-deficient men with a history of favism. Molecular analysis revealed three major different polymorphic variants: G6PD Mediterranean 66.2% (49 out of 74), G6PD Chatham 27% (20 out of 74), G6PD Cosenza 6.75% (5 out of 74). These findings indicated a higher prevalence of G6PD Chatham in this Iranian population than anywhere else in the world. In addition, the distribution of these G6PD variants is more similar to that found in an Italian population than in other Middle Eastern countries.

Oxidative Stress Genes, Antioxidants and Coronary Artery Disease in 
Type 2 Diabetes Mellitus

PubMed Central

Tibaut, Miha; Petrovič, Daniel

2016-01-01

The worldwide increasing prevalence of obesity and sedentary lifestyle is the main cause of the rising incidence of T2DM. Due to chronic macrovascular and microvascular complications, T2DM represent a huge socioeconomic burden in the world. Oxidative stress is a key pathogenic mechanism implicated in diabetic coronary artery disease (CAD). Polymorphisms of oxidative stress genes are known to influence oxidative stress levels and are therefore thought to impact CAD pathogenesis. Identifying higher risk groups would be rational, since it would allow better sample selection and thus better results in antioxidant trials. In this review, we summarize the evidence of oxidative stress gene polymorphisms related to the pathogenesis of CAD. Moreover, we provide a review of antioxidants tested in subjects with CAD. PMID:27052028

Predicting Disease Progression in Scleroderma with Skin and Blood Biomarkers

DTIC Science & Technology

2016-12-01

epidermal differentiation in addition to those involved in extracel- lular matrix production and myofibroblast contractility (35). In a followup study ...important manifestation of SSc are needed. Several studies have linked autoantibody production with genetics in SSc. Multiple polymorphisms in the human...longitudinal clinical data and genetic markers. GENISOS is an inception cohort that avoids survival bias inherent in studies of prevalent cases (mean disease

The common -55 C/T polymorphism in the promoter region of the uncoupling protein 3 gene reduces prevalence of obesity and elevates serum high-density lipoprotein cholesterol levels in the general Japanese population.

PubMed

Hamada, Taku; Kotani, Kazuhiko; Fujiwara, Shinji; Sano, Yoshiko; Domichi, Masayuki; Tsuzaki, Kokoro; Sakane, Naoki

2008-03-01

Uncoupling protein 3 (UCP3) is considered to be associated with obesity, given its function in the regulation of energy and lipid metabolism. An increased body mass index (BMI) and a decreased level of high-density lipoprotein cholesterol (HDL-C) are risk factors for cardiovascular disease. The purpose of this study was to investigate whether the UCP3 promoter -55 C/T single nucleotide polymorphism (UCP3 -55 C/T SNP) was associated with obesity according to the criteria for Japanese (BMI > or = 25 kg/m2), BMI, and serum HDL-C levels in the general Japanese population. The subjects, numbering 282 and aged 65 +/- 13 years (mean +/- SD), were recruited through an annual health checkup of residents of Mima city, Tokushima, in Japan. Body mass index, blood pressure, biochemical indexes including lipid, and lipoprotein profiles were measured. The UCP3 -55 C/T SNP was determined with a fluorescence-based allele-specific DNA primer assay system. The frequency of the -55 T allele was 30.0%. Subjects with the T/T genotype had significantly higher HDL-C levels than those with the C/C genotype or the C/T genotype. Furthermore, subjects with the T/T genotype had a significantly lower BMI than those with the C/C genotype. A multivariate analysis revealed that the -55 T allele was a significant independent variable contributing to the variance in HDL-C levels and BMI. The T/T genotype was associated with a lower prevalence of obesity than the C/C and C/T genotypes, with an odds ratio of 0.358 (95% confidence interval, 0.132-0.972; P = .037). In conclusion, the UCP3 -55 C/T SNP was associated with elevated HDL-C levels and a reduced BMI, independent of modifiable factors such as lifestyle. Furthermore, this polymorphism, when expressed in its homozygous form, reduced the prevalence of obesity in Japanese.

Comparative pharmacogenetic analysis of risk polymorphisms in Caucasian and Vietnamese children with acute lymphoblastic leukemia: prediction of therapeutic outcome?

PubMed

Hoang, Phuong Thu Vu; Ambroise, Jérôme; Dekairelle, Anne-France; Durant, Jean-François; Butoescu, Valentina; Chi, Vu Luan Dang; Huynh, Nghia; Nguyen, Tan Binh; Robert, Annie; Vermylen, Christiane; Gala, Jean-Luc

2015-03-01

Acute lymphoblastic leukemia (ALL) is the most common of all paediatric cancers. Aside from predisposing to ALL, polymorphisms could also be associated with poor outcome. Indeed, genetic variations involved in drug metabolism could, at least partially, be responsible for heterogeneous responses to standardized leukemia treatments, hence requiring more personalized therapy. The aims of this study were to (a) to determine the prevalence of seven common genetic polymorphisms including those that affect the folate and/or thiopurine metabolic pathways, i.e. cyclin D1 (CCND1-G870A), γ-glutamyl hydrolase (GGH-C452T), methylenetetrahydrofolate reductase (MTHFR-C677T and MTHFR-A1298C), thymidylate synthase promoter (TYMS-TSER), thiopurine methyltransferase (TPMT*3A and TPMT*3C) and inosine triphosphate pyrophosphatase (ITPA-C94A), in Caucasian (n = 94, age < 20) and Vietnamese (n = 141, age < 16 years) childhood ALL and (b) to assess the impact of a multilocus genetic risk score (MGRS) on relapse-free survival (RFS) using a Cox proportional-hazards regression model. The prevalence of MTHFR-677TT genotype was significantly higher in Caucasians (P = 0.008), in contrast to the prevalence of TYMS-TSER*3R/3R and ITPA-94AA/AC genotypes which were significantly higher in Vietnamese (P < 0.001 and P = 0.02, respectively). Compared with children with a low MGRS (≤ 3), those with a high MGRS (≥ 4) were 2.06 (95% CI = 1.01, 4.22; P = 0.04) times more likely to relapse. Adding MGRS into a multivariate Cox regression model with race/ethnicity and four clinical variables improved the predictive accuracy of the model (AUC from 0.682 to 0.709 at 24 months). Including MGRS into a clinical model improved the predictive accuracy of short and medium term prognosis, hence confirming the association between well determined pharmacogenotypes and outcome of paediatric ALL. Whether variants on other genes associated with folate metabolism can substantially improve the predictive value of current MGRS is not known but deserves further evaluation. © 2014 The British Pharmacological Society.

Comparative pharmacogenetic analysis of risk polymorphisms in Caucasian and Vietnamese children with acute lymphoblastic leukemia: prediction of therapeutic outcome?

PubMed Central

Vu Hoang, Phuong Thu; Ambroise, Jérôme; Dekairelle, Anne-France; Durant, Jean-François; Butoescu, Valentina; Dang Chi, Vu Luan; Huynh, Nghia; Nguyen, Tan Binh; Robert, Annie; Vermylen, Christiane; Gala, Jean-Luc

2015-01-01

Aims Acute lymphoblastic leukemia (ALL) is the most common of all paediatric cancers. Aside from predisposing to ALL, polymorphisms could also be associated with poor outcome. Indeed, genetic variations involved in drug metabolism could, at least partially, be responsible for heterogeneous responses to standardized leukemia treatments, hence requiring more personalized therapy. The aims of this study were to (a) to determine the prevalence of seven common genetic polymorphisms including those that affect the folate and/or thiopurine metabolic pathways, i.e. cyclin D1 (CCND1-G870A), γ-glutamyl hydrolase (GGH-C452T), methylenetetrahydrofolate reductase (MTHFR-C677T and MTHFR-A1298C), thymidylate synthase promoter (TYMS-TSER), thiopurine methyltransferase (TPMT*3A and TPMT*3C) and inosine triphosphate pyrophosphatase (ITPA-C94A), in Caucasian (n = 94, age < 20) and Vietnamese (n = 141, age < 16 years) childhood ALL and (b) to assess the impact of a multilocus genetic risk score (MGRS) on relapse-free survival (RFS) using a Cox proportional-hazards regression model. Results The prevalence of MTHFR-677TT genotype was significantly higher in Caucasians (P = 0.008), in contrast to the prevalence of TYMS-TSER*3R/3R and ITPA-94AA/AC genotypes which were significantly higher in Vietnamese (P < 0.001 and P = 0.02, respectively). Compared with children with a low MGRS (≤3), those with a high MGRS (≥4) were 2.06 (95% CI = 1.01, 4.22; P = 0.04) times more likely to relapse. Adding MGRS into a multivariate Cox regression model with race/ethnicity and four clinical variables improved the predictive accuracy of the model (AUC from 0.682 to 0.709 at 24 months). Conclusion Including MGRS into a clinical model improved the predictive accuracy of short and medium term prognosis, hence confirming the association between well determined pharmacogenotypes and outcome of paediatric ALL. Whether variants on other genes associated with folate metabolism can substantially improve the predictive value of current MGRS is not known but deserves further evaluation. PMID:25099492

Prevalence of polymorphisms in glucose-6-phosphate dehydrogenase, sickle haemoglobin and nitric oxide synthase genes and their relationship with incidence of uncomplicated malaria in Iganga, Uganda.

PubMed

Lwanira, Catherine Nassozi; Kironde, Fred; Kaddumukasa, Mark; Swedberg, Göte

2017-08-09

Host genetics play an important role in Plasmodium falciparum malaria susceptibility. However, information on host genetic factors and their relationships with malaria in the vaccine trial site of Iganga, Uganda is limited. The main objective of this study was to determine the prevalence of selected host genetic markers and their relationship to malaria incidence in the vaccine trial site of Iganga, Uganda. In a 1-year longitudinal cohort study, 423 children aged below 9 years were recruited and their malaria episodes were investigated. Host genetic polymorphisms were assessed by PCR-RFLP, haemoglobin electrophoresis and DNA sequencing. Using a multivariate negative binomial regression model, estimates of the impact of human genetic polymorphisms on malaria incidence were performed. In all statistical tests, a P value of <0.05 was considered as significant. The prevalences of sickle cell haemoglobin trait, G6PD c.202 G>A (rs 1050828) and NOS2 -954 G>C (rs 1800482) variants were 26.6, 22.7 and 17.3%, respectively. Inducible nitric oxide synthase 2 (NOS2 -954 G>C; rs 1800482) heterozygosity was associated with lower incidence of malaria in all age groups {Adjusted incident rates ratio (aIRR) 0.59; 95% CI [0.386-0.887]; P = 0.012)}. About 4% of study subjects had co-existence of sickle cell Hb trait and G6PD deficiency. Sickle cell Hb heterozygotes (Hb AS) aged less than 1 year experienced significantly more malaria episodes annually than children with normal haemoglobin (Hb AA) {aIRR = 1.98; 95% CI [1.240-3.175]; P = 0.004}. There was no significant influence of the sickle cell trait on malaria incidence among older children of 1-9 years. Mutation (NOS2 -954 G>C; rs 1800482) of nitric oxide synthase 2 gene promoter was associated with a lower incidence of acute malaria. The normal haemoglobin (wild genotype; HbAA) was associated with reduced malaria incidence rates during the first year of life. More understanding of the interplay between host genetics and malaria susceptibility is required.

Association of endothelial nitric oxide synthase gene variants (-786 T>C, intron 4 b/a VNTR and 894 G>T) with idiopathic recurrent pregnancy loss: A case-control study with haplotype and in silico analysis.

PubMed

Azani, Alireza; Hosseinzadeh, Asghar; Azadkhah, Roya; Zonouzi, Ali Akbar Poursadegh; Zonouzi, Ahmad Poursadegh; Aftabi, Younes; Khani, Hourieh; Heidary, Leida; Danaii, Shahla; Bargahi, Nasrin; Pouladi, Nasser; Hosseini, Sayed Mostafa

2017-08-01

Many lines of evidence suggest that reduced production of nitric oxide (NO) due to single nucleotide polymorphisms in endothelial nitric oxide synthase (eNOS) gene may affect the implantation and maintenance of pregnancy. Accordingly, our objective was to investigate whether the eNOS polymorphisms (-786 T>C, intron 4 b/a VNTR and 894 G>T) and haplotypes may be associated with increased susceptibility to recurrent pregnancy loss (RPL). A total of 130 women with a history of two or more unexplained consecutive first trimester miscarriages and 110 ethnically matched women with at least two normal pregnancies and no history of pregnancy loss were included in the study as cases and controls, respectively. To identify the genotypes, we used polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) methods In addition, an in silico analysis was conducted to predict the possible effects of the eNOS 894 G>T polymorphism on the structure and function of eNOS mRNA and protein using prediction servers. Our findings revealed that the prevalence of eNOS -786 T>C polymorphism, eNOS -786C allele and TC+CC genotype in cases were significantly higher than those in healthy controls (p<0.05). Also, the combination genotypes -786TT/4b4a and -786TT/894GG were significantly associated with reduced risk of RPL. We also found that the C-4a-G haplotype of the eNOS gene studied polymorphisms was significantly associated with a predisposition to RPL (odds ratio, 3.219; 95% confidence interval, 1.649-6.282; p=0.0003). The in silico analysis showed that the eNOS 894 G>T polymorphism couldn't affects eNOS mRNA and protein significantly. Our findings provide evidence to support the hypothesis that eNOS -786 T>C polymorphism and the -786C-4a-894G haplotype are associated with the high risk of RPL. Copyright © 2017 Elsevier B.V. All rights reserved.

Renin Gene Polymorphisms in Bangladeshi Hypertensive Population

PubMed Central

Afruza, Rownock; Islam, Laila N; Banerjee, Sajal; Hassan, Md. Mahbub; Suzuki, Fumiaki; Nabi, AHM Nurun

2014-01-01

Objective: Linkages of renin gene polymorphisms with hypertension have been implicated in several populations with contrasting results. Present study aims to assess the pattern of renin gene polymorphisms in Bangladeshi hypertensive individuals. Methodology: Introns 1, 9 of renin gene and 4063 bases upstream of promoter sequence of renin gene were amplified from the genomic DNA of the total 124 (hypertensive and normotensive) subjects using respective primers. Polymerase chain reaction-based restriction fragment length polymorphisms were performed using BglI, MboI and TaqI restriction enzymes. Results: Homozygosity was common in renin gene regarding BglI (bb=48.4%, Bb=37.9%, BB=13.7%, χ2 =1.91, P>0.05), TaqI (TT=81.5%, Tt=14.5%, tt=4.0%, χ2 =7.50, P<0.01) and MboI (mm=63.7%, Mm=32.3%, MM=4.0%, χ2=0.00, P>0.05) polymorphisms among total study population. For BglI and TaqI genotype distribution, hypertensive subjects (BglI: χ2 =6.66, P<0.05; TaqI: χ2 = 10.28, P<0.005) significantly deviate from Hardy-Weinberg Equilibrium law compared to normotensive subjects (BglI: χ2=0.51, P>0.05; TaqI: χ2=0.20, P>0.05). On the other hand, with respect to MboI polymorphisms of renin gene, only normotensive subjects deviate from the law (patients: χ2=1.28, P>0.05; vs controls: χ2=6.81, P<0.01). In the context of allelic frequency, common T allele was clearly prevalent (T frequency=0.86, t frequency = 0.14) for TaqI, but rare alleles b and m were more frequent for both BglI (b frequency=0.69, B frequency=0.31) and MboI (m frequency=0.80 M frequency=0.20) polymorphisms, respectively. Conclusion: Thus, we report that Bangladeshi hypertensive subjects did not show any distinct pattern of renin gene polymorphisms compared to their healthy control subjects with regard to their genotypic and allelic frequencies. PMID:25057323

The association between MCP-1, VEGF polymorphisms and their serum levels in patients with diabetic foot ulcer.

PubMed

Li, Xiaolei

2018-06-01

The purpose of the present study was to investigate distribution of monocyte chemoattractant protein-1 (MCP-1) -2518A/G and vascular endothelial growth factor (VEGF) -634G/C polymorphisms in type 2 diabetes melitus patients (T2DM) presenting diabetic foot ulcer (DFU). Additionally, we evaluated the effects of these 2 polymorphisms on serum levels of MCP-1 and VEGF in the study population.Patients diagnosed with T2DM without or with DFU were recruited in the study. The distribution of MCP-1 -2518A/G and VEGF -634G/C polymorphisms was investigated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Enzyme-linked immunosorbent assay (ELISA) was applied to detect the protein levels of MCP-1 and VEGF. The comparisons of protein levels in DFU patients were performed by student t test according to their genotypes.The frequencies of GG genotype and G allele of MCP-1 -2518A/G was increased in DFU patients, compared with T2DM patients (odds ratio [OR] = 2.60, 95% confidence interval [CI] = 1.23-5.50, P = .011 and OR = 1.72, 95% CI = 1.18-2.50, P = .005, respectively). Moreover, the increased frequency of GG was significantly associated with up-regulated MCP-1 level in DFU patients (P < .001). Analysis for VEGF -634G/C polymorphisms indicated that the prevalence of CC genotype and C allele of the polymorphisms was decreased in DFU patients, compared with T2DM patients (OR = 0.36, 95% CI = 0.17-0.77, P = .008 and OR = 0.63, 95% CI = 0.43-0.91, P = .015, respectively). DFU patients carrying CC genotype had a higher level of VEGF than those with other genotypes (P = .007).MCP-1 -2518A/G and VEGF -634G/C polymorphisms may involve in occurrence and progress of DFU through regulating transcription activity of the genes.

First molecular detection and characterization of Sarcocystis species in slaughtered cattle in North-West Tunisia.

PubMed

Amairia, Safa; Amdouni, Yosra; Rjeibi, Mohamed Ridha; Rouatbi, Mariem; Awadi, Sofia; Gharbi, Mohamed

2016-12-01

Sarcocystis spp. is one of the most prevalent foodborne parasites infecting both animals and humans. Consumption of raw or undercooked infected meat is a risk factor of human intestinal sarcocystosis. The present study aimed to estimate the prevalence of Sarcocystis species infecting slaughtered Tunisian cattle in North-West Tunisia (Béja governorate). DNA was extracted from 150 beef meat samples and a PCR-restriction fragment length polymorphism was used for identification. The overall infection prevalence of Sarcocystis spp. was 38% (57/150). Two species were identified, namely S. hominis (25%; 39/150) and S. cruzi (12%; 18/150). For both species, the highest prevalence was in Thibar locality (52.9 and 17.6% for S. hominis and S. cruzi, respectively). The molecular prevalence of S. cruzi was significantly higher in animals aged between two and eight years (19.2%; 10/52). This is the first molecular identification of Sarcocystis species in Tunisian cattle. Further studies in both human and animal Tunisian populations are needed to rank this parasitic disease among others. Copyright © 2016 Elsevier Ltd. All rights reserved.

Inhibition of chemically induced inflammation and pain by orally and topically administered leaf extract of Manihot esculenta Crantz in rodents.

PubMed

Adeyemi, Olufunmilayo O; Yemitan, Omoniyi K; Afolabi, Lateef

2008-09-02

The aqueous leaf extract of Manihot esculenta Crantz (MELE) is being used orally and topically in traditional African medicine for the treatment of inflammation and pain, and claimed to be safe. The anti-inflammatory effects of MELE (100-400 mg/kg, p.o. or 1-4%, w/w in petroleum jelly, topically) were tested against carrageenan-induced paw oedema in rats as well as against xylene-induced ear oedema in mice. The analgesic effect of MELE (100-400 mg/kg, p.o. or 1-4%, w/w in petroleum jelly, topically) was tested against acetic acid-induced (20 microl, 0.6%, v/v in normal saline, i.p.) and acetylcholine-induced (8.3 mg/kg, i.p.) mouse writhing models. At 100-400 mg/kg, p.o. and 1-4% (w/w), topically, MELE produced significant inhibitions of carrageenan-induced rat paw oedema and xylene-induced ear swelling in mice. Effects produced by MELE were significantly higher than those produced by indomethacin (10 mg/kg, s.c. or 1%, w/w in petroleum jelly) in the anti-inflammatory models. For the analgesic effect, MELE (100-400 mg/kg, orally) and (1-4%, w/w, topically), like aspirin (100 mg/kg, i.p.) exhibited significant (P<0.05) inhibition of acetic acid- and acetylcholine-induced mouse writhing tests, compared to untreated control. Effects produced by MELE were significantly lower than those produced by aspirin (100 mg/kg, i.p.) in the analgesic models, except for the topically administered extract on acetylcholine-induced pain. Acute oral administration up to 10 g/kg did not cause death within 14 days, but mortalities were produced in i.p. administered extract with LD(50) of 2.5+/-0.3 g/kg. Based on these, the extract may contain orally safe, topically and orally effective anti-inflammatory and analgesic principles, which justify its use in traditional African medicine.

Highly efficient mesophyll protoplast isolation and PEG-mediated transient gene expression for rapid and large-scale gene characterization in cassava (Manihot esculenta Crantz).

PubMed

Wu, Jun-Zheng; Liu, Qin; Geng, Xiao-Shan; Li, Kai-Mian; Luo, Li-Juan; Liu, Jin-Ping

2017-03-14

Cassava (Manihot esculenta Crantz) is a major crop extensively cultivated in the tropics as both an important source of calories and a promising source for biofuel production. Although stable gene expression have been used for transgenic breeding and gene function study, a quick, easy and large-scale transformation platform has been in urgent need for gene functional characterization, especially after the cassava full genome was sequenced. Fully expanded leaves from in vitro plantlets of Manihot esculenta were used to optimize the concentrations of cellulase R-10 and macerozyme R-10 for obtaining protoplasts with the highest yield and viability. Then, the optimum conditions (PEG4000 concentration and transfection time) were determined for cassava protoplast transient gene expression. In addition, the reliability of the established protocol was confirmed for subcellular protein localization. In this work we optimized the main influencing factors and developed an efficient mesophyll protoplast isolation and PEG-mediated transient gene expression in cassava. The suitable enzyme digestion system was established with the combination of 1.6% cellulase R-10 and 0.8% macerozyme R-10 for 16 h of digestion in the dark at 25 °C, resulting in the high yield (4.4 × 10 7 protoplasts/g FW) and vitality (92.6%) of mesophyll protoplasts. The maximum transfection efficiency (70.8%) was obtained with the incubation of the protoplasts/vector DNA mixture with 25% PEG4000 for 10 min. We validated the applicability of the system for studying the subcellular localization of MeSTP7 (an H + /monosaccharide cotransporter) with our transient expression protocol and a heterologous Arabidopsis transient gene expression system. We optimized the main influencing factors and developed an efficient mesophyll protoplast isolation and transient gene expression in cassava, which will facilitate large-scale characterization of genes and pathways in cassava.

Validation of Reference Genes for Relative Quantitative Gene Expression Studies in Cassava (Manihot esculenta Crantz) by Using Quantitative Real-Time PCR

PubMed Central

Hu, Meizhen; Hu, Wenbin; Xia, Zhiqiang; Zhou, Xincheng; Wang, Wenquan

2016-01-01

Reverse transcription quantitative real-time polymerase chain reaction (real-time PCR, also referred to as quantitative RT-PCR or RT-qPCR) is a highly sensitive and high-throughput method used to study gene expression. Despite the numerous advantages of RT-qPCR, its accuracy is strongly influenced by the stability of internal reference genes used for normalizations. To date, few studies on the identification of reference genes have been performed on cassava (Manihot esculenta Crantz). Therefore, we selected 26 candidate reference genes mainly via the three following channels: reference genes used in previous studies on cassava, the orthologs of the most stable Arabidopsis genes, and the sequences obtained from 32 cassava transcriptome sequence data. Then, we employed ABI 7900 HT and SYBR Green PCR mix to assess the expression of these genes in 21 materials obtained from various cassava samples under different developmental and environmental conditions. The stability of gene expression was analyzed using two statistical algorithms, namely geNorm and NormFinder. geNorm software suggests the combination of cassava4.1_017977 and cassava4.1_006391 as sufficient reference genes for major cassava samples, the union of cassava4.1_014335 and cassava4.1_006884 as best choice for drought stressed samples, and the association of cassava4.1_012496 and cassava4.1_006391 as optimal choice for normally grown samples. NormFinder software recommends cassava4.1_006884 or cassava4.1_006776 as superior reference for qPCR analysis of different materials and organs of drought stressed or normally grown cassava, respectively. Results provide an important resource for cassava reference genes under specific conditions. The limitations of these findings were also discussed. Furthermore, we suggested some strategies that may be used to select candidate reference genes. PMID:27242878

Status of Vitamins B-12 and B-6 but Not of Folate, Homocysteine, and the Methylenetetrahydrofolate Reductase C677T Polymorphism Are Associated with Impaired Cognition and Depression in Adults123

PubMed Central

Moorthy, Denish; Peter, Inga; Scott, Tammy M.; Parnell, Laurence D.; Lai, Chao-Qiang; Crott, Jimmy W.; Ordovás, José M.; Selhub, Jacob; Griffith, John; Rosenberg, Irwin H.; Tucker, Katherine L.; Troen, Aron M.

2012-01-01

The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene differs in frequency in various ethnic groups that have differing prevalence of age-related cognitive impairments. We used a series of neuro-psychological tests to examine the association of the MTHFR C677T polymorphism with cognition and depression and also to assess whether genotype modifies the association of folate and homocysteine with these outcomes. This study analyzed pooled cross-sectional data from 2 ethnically diverse cohorts of community-living adults: the Boston Puerto Rican Health Study (n = 939) and the Nutrition, Aging, and Memory in Elders study (n = 1017). Individuals in both cohorts underwent anthropometric and laboratory measurements and dietary and health assessments using validated questionnaires between the years 2003 and 2007. Cognitive outcomes included measures of global cognition [Mini-Mental Status Exam (MMSE)], depression (Center for Epidemiological Studies Depression Scale), and 3 factor scores for the domains of attention, executive function, and memory that were derived from a detailed set of neuropsychological tests. Low plasma vitamin B-12 concentrations were associated with poorer MMSE scores and higher depression scores, and low vitamin B-6 concentrations were associated with lower MMSE and worse attention and executive function in the multivariate analysis. In contrast, MTHFR genotype, folate, and homocysteine were not associated with cognition or depression in either ethnicity-pooled or stratified analysis. The current study did not find evidence of an association between the MTHFR C677T TT genotype and impaired cognition or depression in a population with adequate folate status and a high prevalence of cognitive impairment and depression. PMID:22739363

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.

Lack of association between autonomously functioning thyroid nodules and germline polymorphisms of the thyrotropin receptor and Gαs genes in a mild to moderate iodine-deficient Caucasian population.

PubMed

Vicchio, Teresa Manuela; Giovinazzo, Salvatore; Certo, Rosaria; Cucinotta, Mariapaola; Micali, Carmelo; Baldari, Sergio; Benvenga, Salvatore; Trimarchi, Francesco; Campennì, Alfredo; Ruggeri, Rosaria Maddalena

2014-07-01

Mutations of the thyrotropin receptor (TSHR) and/or Gαs gene have been found in a number of, but not all, autonomously functioning thyroid nodules (AFTNs). Recently, in a 15-year-old girl with a hyperfunctioning papillary thyroid carcinoma, we found two somatic and germline single nucleotide polymorphisms (SNPs): a SNP of the TSHR gene (exon 7, codon 187) and a SNP of Gαs gene (exon 8, codon 185). The same silent SNP of the TSHR gene had been reported in patients with AFTN or familial non-autoimmune hyperthyroidism. No further data about the prevalence of the two SNPs in AFTNs as well as in the general population are available in the literature. To clarify the possible role of these SNPs in predisposing to AFTN. Germline DNA was extracted from blood leukocytes of 115 patients with AFTNs (43 males and 72 females, aged 31-85 years, mean ± SD = 64 ± 13) and 100 sex-matched healthy individuals from the same geographic area, which is marginally iodine deficient. The genotype distribution of the two SNPs was investigated by restriction fragment length polymorphism-polymerase chain reaction. The prevalence of the two SNPs in our study population was low and not different to that found in healthy individuals: 8 % of patients vs. 9 % of controls were heterozygous for the TSHR SNP and 4 % patients vs. 6 % controls were heterozygous for the Gαs SNP. One patient harbored both SNPs. These results suggest that these two SNPs do not confer susceptibility for the development of AFTN.

Predictive polymorphisms for breast cancer in postmenopausal Mexican women.

PubMed

Sierra-Martinez, Mónica; Hernández-Cadena, Leticia; García-Sánchez, José Rubén; Acosta-Altamirano, Gustavo; Palacios-Reyes, Carmen; Alonso-Themann, Patricia García; García-Ortiz, Liliana; Quintas-Granados, Laura Itzel; Reyes-Hernández, Octavio Daniel

2018-01-01

Several factors contribute to the increase in breast cancer (BC) incidence, such as lifetime exposure to estrogen, early menarche and older ages at first birth, menopause, and the increased prevalence of postmenopausal obesity. In fact, there is an association between an increased BC risk and elevated estrogen levels, which may be involved in carcinogenesis via the estrogen receptor alpha (ERα) encoded by the ESR1 gene. Interestingly, there is an antagonistic relationship between ERα and the aryl hydrocarbon receptor (AhR) in BC cells. Herein, we explore the combined effects of the ESR1 (XbaI, PvuII) and AhR polymorphisms on BC development in Mexican women according to their menopausal status. Investigation was performed using a cases and controls design. In a group of 96 cases diagnosed with BC and 111 healthy women, the single-nucleotide polymorphisms ESR1 (XbaI, PvuII) and AhR gene were identified by qPCR. Chi-square test or Fisher's exact test were used. Statistical analyses were conducted using the STATA statistical package (Version 10.1, STATA Corp., College Station, TX, USA). The G/G XbaI genotype was more prevalent in the cases than in the controls (P = 0.008). Moreover, Mexican women carrying the XbaI (wild type [WT]/G or G/G) ESR1 genotype have higher risk (12.26-fold) for developing postmenopausal BC than individuals carrying the WT/WT genotype. The presence of the G/G genotype of XbaI may be considered a susceptibility allele in Mexican women. Due to increased postmenopausal BC risk, the XbaI (WT/G or G/G) alleles may be used as a postmenopausal predictive factor for BC in Mexican women.

MTHFR GENE C677T POLYMORPHISM AND LEVELS OF DNA METHYLTRASFERASES IN SUBCLINICAL HYPOTHYROIDISM.

PubMed

Kvaratskhelia, T; Kvaratskhelia, E; Kankava, K; Abzianidze, E

2017-04-01

The aim of our study was to investigate the link between MTHFR gene C677T polymorphism and DNMTs levels in patients with Subclinical Hypothyroidism (SCH). In this study 19 adult patients with subclinical hypothyroidism and 19 healthy controls (mean age 31±5.5 and 33±5.1 years respectively) were recruited. All patients were diagnosed based on serum levels of TSH, FT4, anti-TG and anti-TPO antibodies. Written informed consents were obtained from all study subjects. Genomic DNA was extracted using Quick-DNA Universal Kit (Zymo Research, USA). The MTHFR C677T polymorphism was genotyped by PCR-RFLP method. Levels of DNMT1 and 3a were measured in nuclear extracts of PBMC using DNMTs assay kits (Abcam). Our data indicates that the frequency of genotypes and alleles were different among the patient and the control group. There is a significant increase in CC genotype distribution in the control group when compared to the SCH patient group, while the CT as well as TT genotype distribution were not increased significantly in SCH group versus control group. However the C allele is significantly prevalent in the control group compared to the SCH group, while T allele is prevalent in patients compared to the control group with a statically significant difference. In addition, individuals with TT and CT genotypes and hypothyroidism showed elevated amount of DNMT3a in nuclear extracts of PBMC compared with controls, while no significant difference in DNMT1 levels was observed. This study indicates the MTHFR C677T variant may contribute in alteration of epigenetic regulation such as DNA methylation mediated by DNA methyltransferases in patients with subclinical hypothyroidism and also, carriers of the T allele might have an increasing risk of developing SCH.

Analysis of RANKL gene polymorphism (rs9533156 and rs2277438) in Iranian patients with chronic periodontitis and periimplantitis.

PubMed

Kadkhodazadeh, Mahdi; Ebadian, Ahmad Reza; Gholami, Gholam Ali; Khosravi, Alireza; Tabari, Zahra Alizadeh

2013-05-01

RANK/OPG/RANKL pathway plays a significant role in osteoclastogenesis, osteoclast activation, and regulation of bone resorption. The aim of this study was to investigate the association of RANKL gene polymorphisms (rs9533156 and rs2277438) with chronic periodontitis and peri-implantitis in an Iranian population. 77 patients with chronic periodontitis, 40 patients with peri-implantitis and 89 periodontally healthy patients were enrolled in this study. 5cc of blood was obtained from the cephalic vein of subjects arms and transferred into tubes containing EDTA. Genomic DNA was extracted using Miller's Salting Out technique. The DNA was transferred into 96 division plates, transported to Kbioscience Institute in United Kingdom and analyzed using the Kbioscience Competitive Allele Specific PCR (KASP) technique. Differences in the frequencies of genotypes and alleles in the disease and control groups were analyzed using Chi-square and Fisher's exact statistical tests. Comparison of frequency of alleles in SNP rs9533156 of RANKL gene between the chronic periodontitis group with the control and peri-implantitis groups revealed statistically significant differences (P=0.024 and P=0.027, respectively). Comparison of genotype expression of SNP rs9533156 on RANKL gene between the peri-implantitis group with chronic periodontitis and control groups revealed statistically significant differences (P=0.001); the prevalence of CT genotype was significantly higher amongst the chronic periodontitis group. Regarding SNP rs2277438 of RANKL gene, comparison of prevalence of genotypes and frequency of alleles did not reveal any significant differences (P=0.641/P=0.537, respectively). The results of this study indicate that CT genotype of rs9533156 RANKL gene polymorphism was significantly associated with peri-implantitis, and may be considered as a genetic determinant for peri-implantitis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Polymorphisms of CYP1A2 and CYP2A6 activity: phenotypes and the effect of age and sex in a Nigerian population.

PubMed

Adehin, Ayorinde; Bolaji, Oluseye O

2015-09-01

CYP1A2 and CYP2A6 are polymorphic enzymes that metabolise several compounds of clinical importance. This study investigated the prevalent phenotypes of these enzymes and the influence of age and sex on enzyme activity in a Nigerian population. Caffeine (110 mg) was administered to each of 129 healthy, unrelated subjects (85 males and 44 females) who were non-smokers. Urine voided within 7 h after caffeine administration was collected for a high performance liquid chromatographic assay of caffeine (137X), 1,7-dimethyluric acid (17U) and 1,7-dimethylxanthine (17X). CYP1A2 activity was measured as a ratio of (17U+17X) to 137X, while 17U/17X served as marker for CYP2A6. Transformed data were analysed and the influences of age and sex on activity were also determined. Distribution of CYP1A2 activity in the population was bimodal with a mean±SD of 0.82±0.41, while that of CYP2A6 was trimodal with a mean±SD activity of 0.27±0.42 of the log-transformed urinary molar ratio of metabolites. The influences of age and sex on enzyme activity for both CYP1A2 and CYP2A6 were not significant (p>0.05). The study established the prevalence of polymorphism in phenotypes of CYP1A2 and CYP2A6 activity in the Nigerian population, but no influence of age and sex on enzyme activity was observed in this population.

Molecular detection and prevalence of feline hemotropic mycoplasmas in Istanbul, Turkey.

PubMed

Cetinkaya, Handan; Haktanir, Damla; Arun, Seckin; Vurusaner, Cem

2016-01-01

The aim of this study was to investigate Mycoplasma spp. species in blood samples of the domestic cats from the province of Istanbul, Turkey. Three hundred eighty four blood samples of client-owned cats were used for the identification of Mycoplasma haemofelis (Mhf), Candidatus Mycoplasma haemominutum (CMhm) and Candidatus Mycoplasma turicensis (CMt) by Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) assays. Out of 384 blood samples, 74 (19.3%) were positive for one of Mycoplasma species. The total prevalence of Mhf, CMhm and CMt infections was 9.9%, 17.7% and 0.8% respectively. The most common species was CMhm. Co-infections were mostly with Mhf/CMhm and the frequency was 8.1%. Two cats were infected with three species. The current study was the first molecular prevalence study of hemotropic mycoplasmas in Istanbul, reporting the presence of CMt for the first time in Turkey. Prevalence of feline mycoplasma was notably high in Istanbul and PCR assay could be preferred rather than the microscopic examination for the diagnosis.

Association between FokI, ApaI and TaqI RFLP polymorphisms in VDR gene and Hashimoto's thyroiditis: preliminary data from female patients in Serbia.

PubMed

Djurovic, J; Stojkovic, O; Ozdemir, O; Silan, F; Akurut, C; Todorovic, J; Savic, K; Stamenkovic, G

2015-06-01

Hashimoto's thyroiditis (HT) is the most prevalent autoimmune thyroid disorder caused by an interaction between genes and environmental triggers. Intrathyroid lymphocytic infiltration may lead to progressive destruction of thyroid tissue and consequently to hypothyroidism. Many studies in different populations have shown association between vitamin D receptor (VDR) gene polymorphisms and various autoimmune diseases, including HT. The study included 44 female patients (mean age ± standard deviation 38 ± 5.4) with Hashimoto's thyroiditis and 32 healthy age-matched, sex-matched and geographically matched controls without personal history of autoimmune and endocrine diseases. Genomic DNA was isolated from peripheral blood-EDTA, and the target VDR gene was genotyped by PCR-RFLP technique after VDR-FokI (rs2228570), VDR-ApaI (rs7975232) and VDR-TaqI (rs731236) restriction enzymes digestion. We used spss 20.0 integrated software for data analysis and found a significant difference in the genotype distribution of VDR-FokI polymorphism between patients with HT and controls (P = 0.009). For ApaI and TaqI, we observed a higher frequency of variant allele in patients with HT, which was not significantly different compared to control women (P > 0.05). The current first and preliminary results identified the association between VDR-FokI gene polymorphism and Hashimoto's thyroiditis in Serbian population. Results need to be supported by further investigations that define haplotype patterns for VDR gene polymorphisms in a larger group of HT patients of both sexes. © 2015 John Wiley & Sons Ltd.

The Q705K and F359L Single-Nucleotide Polymorphisms of NOD-Like Receptor Signaling Pathway: Association with Chronic Pancreatitis, Pancreatic Cancer, and Periodontitis.

PubMed

Miskiewicz, Andrzej; Szparecki, Grzegorz; Durlik, Marek; Rydzewska, Grażyna; Ziobrowski, Ireneusz; Górska, Renata

2015-12-01

The aim of this study was to establish the correlation between the occurrence of Q705K and F359L polymorphisms in patients diagnosed with pancreatic diseases and periodontal conditions of various degrees of severity. The above-mentioned genetic markers were assessed in patients with pancreatic cancer (n = 18) and chronic pancreatitis (n = 39) as well as in a healthy control group (n = 115). The established inclusion criteria were the following: Caucasian descent, non-smoking, and age range 20-80, with different levels of periodontitis activity according to S. Offenbacher's scale. The genotyping reactions were performed by means of an RT-PCR with the use of TaqMan(®) genotyping assay. Results of the study revealed that the state of periodontium was significantly worse in patients with chronic pancreatitis. The Q705K and F359L polymorphisms were associated with more advanced cases of periodontitis measured by clinical attachment level, whereas the Q705K was associated with intensified bleeding index. Furthermore, the F359L single-nucleotide polymorphism was significantly higher in the group with chronic pancreatitis (p < 0.0001; OR = 6.8571). Whereas, the prevalence of Q705K polymorphism was higher in the group of pancreatic cancer (p = 0.107; OR = 3.3939). This study suggests that the exaggerated inflammatory response provoked by Q705K and F359L might be the common denominator for periodontitis, pancreatic cancer, and chronic pancreatitis. These findings might constitute the basis for a new diagnostic and therapeutic approach.

Polymorphisms of genes involved in polycyclic aromatic hydrocarbons’ biotransformation and atherosclerosis

PubMed Central

Marinković, Natalija; Pašalić, Daria; Potočki, Slavica

2013-01-01

Polycyclic aromatic hydrocarbons (PAHs) are among the most prevalent environmental pollutants and result from the incomplete combustion of hydrocarbons (coal and gasoline, fossil fuel combustion, byproducts of industrial processing, natural emission, cigarette smoking, etc.). The first phase of xenobiotic biotransformation in the PAH metabolism includes activities of cytochrome P450 from the CYP1 family and microsomal epoxide hydrolase. The products of this biotransformation are reactive oxygen species that are transformed in the second phase through the formation of conjugates with glutathione, glucuronate or sulphates. PAH exposure may lead to PAH-DNA adduct formation or induce an inflammatory atherosclerotic plaque phenotype. Several genetic polymorphisms of genes encoded for enzymes involved in PAH biotransformation have been proven to lead to the development of diseases. Enzyme CYP P450 1A1, which is encoded by the CYP1A1 gene, is vital in the monooxygenation of lipofilic substrates, while GSTM1 and GSTT1 are the most abundant isophorms that conjugate and neutralize oxygen products. Some single nucleotide polymorphisms of the CYP1A1 gene as well as the deletion polymorphisms of GSTT1 and GSTM1 may alter the final specific cellular inflammatory respond. Occupational exposure or conditions from the living environment can contribute to the production of PAH metabolites with adverse effects on human health. The aim of this study was to obtain data on biotransformation and atherosclerosis, as well as data on the gene polymorphisms involved in biotransformation, in order to better study gene expression and further elucidate the interaction between genes and the environment. PMID:24266295

The Effect of ACE I/D Polymorphisms Alone and With Concomitant Risk Factors on Coronary Artery Disease.

PubMed

Amara, Ahmed; Mrad, Meriem; Sayeh, Aicha; Lahideb, Dhaker; Layouni, Samy; Haggui, Abdeddayem; Fekih-Mrissa, Najiba; Haouala, Habib; Nsiri, Brahim

2018-01-01

Coronary artery disease (CAD), also known as atherosclerotic heart disease, is a leading cause of mortality and morbidity throughout the world. The role of insertion/deletion (I/D) polymorphisms of the angiotensin-converting enzyme (ACE) gene in the etiology of CAD remains to be more completely clarified. The aim of this study was to determine the role of the ACE I/D polymorphism in patients with CAD and to study the association together with traditional risk factors in assessing the risk of CAD. Our study population included 145 Tunisian patients with symptomatic CAD and a control group of 300 people matched for age and sex. All participants in the study were genotyped for the ACE I/D polymorphisms obtained by polymerase chain reaction amplification on genomic DNA. Our analysis showed that the ACE D allele frequency ( P < 10 -3 ; odds ratio [OR] = 5.2; 95% confidence interval [CI] = 3.6-7.6) and DD genotype ( P < 10 -3 ; OR = 6.8; 95% CI = 4.4-10) are significantly more prevalent among patients with CAD than in controls and may be predisposing to CAD. We further found that the risk of CAD is greatly potentiated by several concomitant risk factors (smoking, diabetes, hypertension, dyslipidemia, and a family history of CAD). The ACE D allele may be predictive in individuals who may be at risk of developing CAD. Further investigations of these polymorphisms and their possible synergisms with traditional risk factors for CAD could help to ascertain better predictability for CAD susceptibility.

Polymorphisms in Plasmodium falciparum Chloroquine Resistance Transporter and Multidrug Resistance 1 Genes: Parasite Risk Factors that Affect Treatment Outcomes for P. falciparum Malaria after Artemether-Lumefantrine and Artesunate-Amodiaquine

PubMed Central

Venkatesan, Meera; Gadalla, Nahla B.; Stepniewska, Kasia; Dahal, Prabin; Nsanzabana, Christian; Moriera, Clarissa; Price, Ric N.; Mårtensson, Andreas; Rosenthal, Philip J.; Dorsey, Grant; Sutherland, Colin J.; Guérin, Philippe; Davis, Timothy M. E.; Ménard, Didier; Adam, Ishag; Ademowo, George; Arze, Cesar; Baliraine, Frederick N.; Berens-Riha, Nicole; Björkman, Anders; Borrmann, Steffen; Checchi, Francesco; Desai, Meghna; Dhorda, Mehul; Djimdé, Abdoulaye A.; El-Sayed, Badria B.; Eshetu, Teferi; Eyase, Frederick; Falade, Catherine; Faucher, Jean-François; Fröberg, Gabrielle; Grivoyannis, Anastasia; Hamour, Sally; Houzé, Sandrine; Johnson, Jacob; Kamugisha, Erasmus; Kariuki, Simon; Kiechel, Jean-René; Kironde, Fred; Kofoed, Poul-Erik; LeBras, Jacques; Malmberg, Maja; Mwai, Leah; Ngasala, Billy; Nosten, Francois; Nsobya, Samuel L.; Nzila, Alexis; Oguike, Mary; Otienoburu, Sabina Dahlström; Ogutu, Bernhards; Ouédraogo, Jean-Bosco; Piola, Patrice; Rombo, Lars; Schramm, Birgit; Somé, A. Fabrice; Thwing, Julie; Ursing, Johan; Wong, Rina P. M.; Zeynudin, Ahmed; Zongo, Issaka; Plowe, Christopher V.; Sibley, Carol Hopkins

2014-01-01

Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in pfcrt and pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ. Presence of the pfmdr1 gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval = 2.29 – 9.78, P < 0.001) and increased pfmdr1 copy number (adjusted hazards ratio = 6.52, 95% confidence interval = 2.36–17.97, P < 0.001) were significant independent risk factors for recrudescence in patients treated with AL. AL and ASAQ exerted opposing selective effects on single-nucleotide polymorphisms in pfcrt and pfmdr1. Monitoring selection and responding to emerging signs of drug resistance are critical tools for preserving efficacy of artemisinin combination therapies; determination of the prevalence of at least pfcrt K76T and pfmdr1 N86Y should now be routine. PMID:25048375

Association between glutathione S-transferase pi genetic polymorphisms and oral cancer risk.

PubMed

Park, J Y; Schantz, S P; Stern, J C; Kaur, T; Lazarus, P

1999-08-01

Polymorphisms in the gene encoding the glutathione S-transferase (GST) pi metabolizing enzyme have previously been associated with susceptibility to various cancers. In this study, the importance of GSTP1 genotypes as determinants of risk for oral cancer was assessed by examining the prevalence of GSTP1 alleles in 157 incident oral cancer cases and 260 non-cancer control individuals frequency-matched by race, sex, and age at diagnosis (+/- 5 years). The GSTP1*A, GSTP1*B, GSTP1*C, and GSTP1*D alleles were elucidated by polymerase chain reaction-restriction fragment length polymorphism analysis of polymorphisms present in codons 105 (isoleucine:valine) and 114 (alanine:valine) of the GSTP1 gene. Increased risk for oral cancer was observed in individuals who were homozygous for any combination of GSTP1 polymorphic alleles (i.e. *B, *C, and/or *D alleles; odds ratio = 2.4, 95% confidence interval = 1.2-4.8). Similar risk was observed in both Caucasians (odds ratio = 2.6, 95% confidence interval = 1.1-6.2) and African-Americans (odds ratio = 2.3, 95% CI = 0.68-7.5). A greater risk was observed in individuals with the GSTP1 (Var/Var) genotype who were exposed to low levels of smoking (i.e. < or = 20 pack-years [py], odds ratio = 3.4, 95% confidence interval = 1.1-11) than among heavier smokers (i.e. > 20 pack-years [py], odds ratio = 1.4, 95% confidence interval = 0.48-4.0). These results suggest that GSTP1 genotype may play a role in risk for oral cancer particularly among lighter smokers.

Characterization of natural polymorphic sites of the HIV-1 integrase before the introduction of HIV-1 integrase inhibitors in Germany

PubMed Central

Meixenberger, Karolin; Pouran Yousef, Kaveh; Somogyi, Sybille; Fiedler, Stefan; Bartmeyer, Barbara; von Kleist, Max; Kücherer, Claudia

2014-01-01

Introduction The aim of our study was to analyze the occurrence and evolution of HIV-1 integrase polymorphisms during the HIV-1 epidemic in Germany prior to the introduction of the first integrase inhibitor raltegravir in 2007. Materials and Methods Plasma samples from drug-naïve HIV-1 infected individuals newly diagnosed between 1986 and 2006 were used to determine PCR-based population sequences of the HIV-1 integrase (amino acids 1–278). The HIV-1 subtype was determined using the REGA HIV-1 subtyping tool. We calculated the frequency of amino acids at each position of the HIV-1 integrase in 337 subtype B strains for the time periods 1986–1989, 1991–1994, 1995–1998, 1999–2002, and 2003–2006. Positions were defined as polymorphic if amino acid variation was >1% in any period. Logistic regression was used to identify trends in amino acid variation over time. Resistance-associated mutations were identified according to the IAS 2013 list and the HIVdb, ANRS and GRADE algorithms. Results Overall, 56.8% (158/278) amino acid positions were polymorphic and 15.8% (25/158) of these positions exhibited a significant trend in amino acid variation over time. Proportionately, most polymorphic positions (63.3%, 31/49) were detected in the N-terminal zinc finger domain of the HIV-1 integrase. Motifs and residues essential for HIV-1 integrase activity were little polymorphic, but within the minimal non-specific DNA binding region I220-D270 up to 18.1% amino acid variation was noticed, including four positions with significant amino acid variation over time (S230, D232, D256, A265). No major resistance mutations were identified, and minor resistance mutations were rarely observed without trend over time. E157Q considered by HIVdb, ANRS, and GRADE algorithms was the most frequent resistance-associated polymorphism with an overall prevalence of 2.4%. Conclusions Detailed knowledge of the evolutionary variation of HIV-1 integrase polymorphisms is important to understand the development of resistance in the presence of the drug. Our results will contribute to define the relevance of integrase polymorphisms in HIV-strains resistant to integrase inhibitors and to improve resistance interpretation algorithms. PMID:25397491

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

Study of the leptin levels and its gene polymorphisms in patients with idiopathic short stature and growth hormone deficiency.

PubMed

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

2012-08-01

Leptin levels may regulate fat metabolism, skeletal growth, and puberty. Leptin gene variants affect risk of obesity, cancer, but their effect on onset of growth hormone deficiency (GHD) and idiopathic short stature (ISS) is unknown. We tested the hypothesis that the phenotype of GHD and ISS may be associated with polymorphism in the leptin gene. The prevalence of a single nucleotide polymorphism (SNP) in the leptin gene (LEP) promoter at -2548 and the leptin and insulin growth factor-1 (IGF-1) concentrations in GHD and ISS were compared to those of healthy controls. IGF-1 and leptin concentrations were significantly lower in both the GHD and ISS groups than in the control group. The ISS and GHD groups had a significantly different distribution of SNP alleles at the LEP -2548 (P = 0.010). Individuals with LEP -2548A/G or G/G genotype in ISS group (47.5%) showed a significantly lower weight and body mass index (BMI) (but not leptin levels) than individuals carrying the A/A genotype (52.5%). LEP -2548A/A in GHD patients (65.8%) was associated with lower weight, BMI, leptin concentrations than those of individuals carrying the A/G or G/G genotype (34.2%). These data suggest that the LEP -2548A polymorphism may associate with the weight and BMI of the children with ISS and GHD.

Nutrient Intake, Apolipoprotein A5 -1131T>C Polymorphism and Its Relationship with Obesity

NASA Astrophysics Data System (ADS)

Sari, M. I.; Sari, D. I.

2017-03-01

Obesity is associated with the development of some of the most prevalent diseases of modern society. The World Health Organization estimates that at least 2.8 million adult die each year as result of being obesity. Nutrient intake is a key environmental factor that may interact with genotype to affect risk of obesity. The aim of study was assess the relation between nutrient intake and apolipoprotein A5 -1131T>C polimorphism with obesity. A cross sectional study has been carried out on 139 subjects. Nutrient intake data was collected by using a 24 hour dietary recall and analyzed by nutrisurvey software. Anthropometric variables were measured and body mass index (BMI). Apolipoprotein A5 -1131T>C polymorphism was visualized with 5% agarose gel after restriction length fragment polymorphism (RFLP) digested with MseI. Results : Subjects in this study were 55 male and 84 female, with average age 19.20 ± 1.08, 75 had obese and 64 non obese. Based on the chi square test is found a relationship between total energy intake and protein intake in obese group compared to the non-obese group (p = 0.029, p = 0.006) and no relationship was found in Apolipoprotein A5 -1131T> C polymorphism with obesity. These findings indicate that nutrient intake no depending with apolipoprotein A5 gene variant to modulate obesity

Absence of Putative Artemisinin Resistance Mutations Among Plasmodium falciparum in Sub-Saharan Africa: A Molecular Epidemiologic Study

PubMed Central

Taylor, Steve M.; Parobek, Christian M.; DeConti, Derrick K.; Kayentao, Kassoum; Coulibaly, Sheick Oumar; Greenwood, Brian M.; Tagbor, Harry; Williams, John; Bojang, Kalifa; Njie, Fanta; Desai, Meghna; Kariuki, Simon; Gutman, Julie; Mathanga, Don P.; Mårtensson, Andreas; Ngasala, Billy; Conrad, Melissa D.; Rosenthal, Philip J.; Tshefu, Antoinette K.; Moormann, Ann M.; Vulule, John M.; Doumbo, Ogobara K.; ter Kuile, Feiko O.; Meshnick, Steven R.; Bailey, Jeffrey A.; Juliano, Jonathan J.

2015-01-01

Plasmodium falciparum parasites that are resistant to artemisinins have been detected in Southeast Asia. Resistance is associated with several polymorphisms in the parasite's K13-propeller gene. The molecular epidemiology of these artemisinin resistance genotypes in African parasite populations is unknown. We developed an assay to quantify rare polymorphisms in parasite populations that uses a pooled deep-sequencing approach to score allele frequencies, validated it by evaluating mixtures of laboratory parasite strains, and then used it to screen P. falciparum parasites from >1100 African infections collected since 2002 from 14 sites across sub-Saharan Africa. We found no mutations in African parasite populations that are associated with artemisinin resistance in Southeast Asian parasites. However, we observed 15 coding mutations, including 12 novel mutations, and limited allele sharing between parasite populations, consistent with a large reservoir of naturally occurring K13-propeller variation. Although polymorphisms associated with artemisinin resistance in P. falciparum in Southeast Asia are not prevalent in sub-Saharan Africa, numerous K13-propeller coding polymorphisms circulate in Africa. Although their distributions do not support a widespread selective sweep for an artemisinin-resistant phenotype, the impact of these mutations on artemisinin susceptibility is unknown and will require further characterization. Rapid, scalable molecular surveillance offers a useful adjunct in tracking and containing artemisinin resistance. PMID:25180240

Apolipoprotein E polymorphisms in Japanese patients with polypoidal choroidal vasculopathy and exudative age-related macular degeneration.

PubMed

Gotoh, Norimoto; Kuroiwa, Sachiko; Kikuchi, Takanobu; Arai, Jun; Arai, Satoko; Yoshida, Noriko; Yoshimura, Nagahisa

2004-10-01

To study the genotypes, allelic frequencies, and polymorphisms of apolipoprotein E (Apo E) in unrelated Japanese patients with polypoidal choroidal vasculopathy (PCV) or exudative age-related macular degeneration (AMD) and control subjects without macular degeneration. Cross-sectional study. Blood samples from 225 subjects older than 50 years were used. The 225 subjects included 58 patients with PCV, 85 with AMD, and 82 without macular degeneration. Coding exons of the Apo E gene were amplified by polymerase chain reaction, and the DNA sequences were determined by direct sequencing with an automated sequencer. Apo E epsilon3/epsilon3 was the most frequent genotype with a prevalence of 79.3% in PCV patients, 76.5% in AMD patients, and 67.1% in the control subjects. However, the differences in the percentages were not statistically significant among the three groups. The most frequently found allele in the three groups was epsilon3. Patients with PCV and AMD were less likely to have epsilon2 and epsilon4 than the control subjects, but the differences were not statistically significant. Five minor Apo E single nucleotide polymorphisms, including epsilon5 and epsilon7, were found. Japanese patients with PCV and AMD were less likely to have epsilon2 and epsilon4 polymorphisms, but the differences from the normals were not statistically significant for the Apo E genotypes and allelic frequencies.

Genetic diversity and prevalence of CCR2-CCR5 gene polymorphisms in the Omani population

PubMed Central

Al-Mahruqi, Samira H.; Zadjali, Fahad; Beja-Pereira, Albano; Koh, Crystal Y.; Balkhair, Abdullah; Al-Jabri, Ali A.

2014-01-01

Polymorphisms in the regulatory region of the CCR5 gene affect protein expression and modulate the progress of HIV-1 disease. Because of this prominent role, variations in this gene have been under differential pressure and their frequencies vary among human populations. The CCR2V64I mutation is tightly linked to certain polymorphisms in the CCR5 gene. The current Omani population is genetically diverse, a reflection of their history as traders who ruled extensive regions around the Indian Ocean. In this study, we examined the CCR2-CCR5 haplotypes in Omanis and compared the patterns of genetic diversity with those of other populations. Blood samples were collected from 115 Omani adults and genomic DNA was screened to identify the polymorphic sites in the CCR5 gene and the CCR2V64I mutation. Four minor alleles were common: CCR5-2554T and CCR5-2086G showed frequencies of 49% and 46%, respectively, whereas CCR5-2459A and CCR5-2135C both had a frequency of 36%. These alleles showed moderate levels of heterozygosity, indicating that they were under balancing selection. However, the well-known allele CCR5Δ32 was relatively rare. Eleven haplotypes were identified, four of which were common: HHC (46%), HHE (20%), HHA (14%) and HHF*2 (12%). PMID:24688285

[PAL-1 5G/4G polymorphism in patients with systemic lupus erythematosus].

PubMed

Savov, A; Andonova, S; Tanev, D; Robeva, R; Marincheva, Ts; Tomova, A; Kumanov, Ph; Rashkov, R; Kolarov, Zl

2014-01-01

Systemic lupus erythematosus (SLE) is a connective tissue disease affecting predominantly women that has been widely associated with obstetric complications. Inherited thrombophilias are significant risk factors for pregnancy loss, but their role in patients with SLE, and especially in those without concomitant secondary antiphospholipid syndrome (APS) has not been clarified. The aim of the present study was to study PAI-1 5G/4G polymorphism in women with lupus. A total of 103 SLE patients as well as 69 healthy volunteers were genotyped for PAI-1 5G/4G (rs1799889). No significant differences in the PAI-1 5G/4G genotype prevalence between patients and controls were found. After exclusion of the women with secondary APS, the frequency of pregnancies and spontaneous abortions, as well as the number of live births were similar in the studied patients with different PAI-1 genotype (p> 0.05). PAI-1 5G/4G polymorphism was not significantly related to any of the lupus ACR criteria or disease activity (p > 0.05), but it could influence the platelet number in the studied patients (263.52 ± 91.10 [5G/5G genotype] versus 210.12 ± 71.79 [4G/4G genotype], p = 0.023). In conclusion, our results showed that PAI-1 4G/5G polymorphism did not worsen the reproductive outcome in SLE women without secondary APS.

Association of BDNF Val66Met polymorphism with HPA and SAM axis reactivity to psychological and physical stress.

PubMed

Tsuru, Jusen; Tanaka, Yoshihiro; Ishitobi, Yoshinobu; Maruyama, Yoshihiro; Inoue, Ayako; Kawano, Aimi; Ikeda, Rie; Ando, Tomoko; Oshita, Harumi; Aizawa, Saeko; Masuda, Koji; Higuma, Haruka; Kanehisa, Masayuki; Ninomiya, Taiga; Akiyoshi, Jotaro

2014-01-01

Decreased expression of brain-derived neurotrophic factor (BDNF) is implicated in enhanced stress responses. The BDNF Val66Met polymorphism is associated with psychological changes; for example, carriers of the Met allele exhibit increased harm avoidance as well as a higher prevalence of depression and anxiety disorder. To analyze the effects of BDNF Val66Met on stress responses, we tested 226 university students (88 women and 138 men) using a social stress procedure (Trier Social Stress Test [TSST]) and an electrical stimulation stress test. Stress indices were derived from repeated measurements of salivary α-amylase, salivary cortisol, heart rate, and psychological testing during the stress tests. All subjects were genotyped for the Val66Met polymorphism (G196A). A significant three-way interaction (time [3 levels] × BDNF [Val/Val, Val/Met, Met/Met]; P<0.05) was demonstrated that revealed different salivary cortisol responses in the TSST but not in electrical stimulation. Met/Met women had stronger cortisol responses than Val/Met and Val/Val individuals in the TSST. Met/Met men exhibited stronger salivary cortisol responses than Val/Met and Val/Val individuals in the TSST. These results indicate that a common, functionally significant polymorphism in BDNF had different effects on hypothalamic-pituitary-adrenocortical axis reactivity but not on sympathetic adrenomedullary reactivity in TSST and electrical stimulation tests.

Triglyceride associated polymorphisms of the APOA5 gene have very different allele frequencies in Pune, India compared to Europeans

PubMed Central

Chandak, Giriraj R; Ward, Kirsten J; Yajnik, Chittaranjan S; Pandit, Anand N; Bavdekar, Ashish; Joglekar, Charu V; Fall, Caroline HD; Mohankrishna, P; Wilkin, Terence J; Metcalf, Bradley S; Weedon, Michael N; Frayling, Timothy M; Hattersley, Andrew T

2006-01-01

Background The APOA5 gene variants, -1131T>C and S19W, are associated with altered triglyceride concentrations in studies of subjects of Caucasian and East Asian descent. There are few studies of these variants in South Asians. We investigated whether the two APOA5 variants also show similar association with various lipid parameters in Indian population as in the UK white subjects. Methods We genotyped 557 Indian adults from Pune, India, and 237 UK white adults for -1131T>C and S19W variants in the APOA5 gene, compared their allelic and genotype frequency and determined their association with fasting serum triglycerides, total cholesterol, HDL and LDL cholesterol levels using univariate general linear analysis. APOC3 SstI polymorphism was also analyzed in 175 Pune Indian subjects for analysis of linkage disequilibrium with the APOA5 variants. Results The APOA5 -1131C allele was more prevalent in Indians from Pune (Pune Indians) compared to UK white subjects (allele frequency 20% vs. 4%, p = 0.00001), whereas the 19W allele was less prevalent (3% vs. 6% p = 0.0015). Patterns of linkage disequilibrium between the two variants were similar between the two populations and confirmed that they occur on two different haplotypes. In Pune Indians, the presence of -1131C allele and the 19W allele was associated with a 19% and 15% increase respectively in triglyceride concentrations although only -1131C was significant (p = 0.0003). This effect size was similar to that seen in the UK white subjects. Analysis of the APOC3 SstI polymorphism in 175 Pune Indian subjects showed that this variant is not in appreciable linkage disequilibrium with the APOA5 -1131T>C variant (r2 = 0.07). Conclusion This is the first study to look at the role of APOA5 in Asian Indian subjects that reside in India. The -1131C allele is more prevalent and the 19W allele is less prevalent in Pune Indians compared to UK Caucasians. We confirm that the APOA5 variants are associated with triglyceride levels independent of ethnicity and that this association is similar in magnitude in Asian Indians and Caucasians. The -1131C allele is present in 36% of the Pune Indian population making it a powerful marker for looking at the role of elevated triglycerides in important conditions such as pancreatitis, diabetes and coronary heart disease. PMID:17032446

Development and application of transgenic technologies in cassava.

PubMed

Taylor, Nigel; Chavarriaga, Paul; Raemakers, Krit; Siritunga, Dimuth; Zhang, Peng

2004-11-01

The capacity to integrate transgenes into the tropical root crop cassava (Manihot esculenta Crantz) is now established and being utilized to generate plants expressing traits of agronomic interest. The tissue culture and gene transfer systems currently employed to produce these transgenic cassava have improved significantly over the past 5 years and are assessed and compared in this review. Programs are underway to develop cassava with enhanced resistance to viral diseases and insects pests, improved nutritional content, modified and increased starch metabolism and reduced cyanogenic content of processed roots. Each of these is described individually for the underlying biology the molecular strategies being employed and progress achieved towards the desired product. Important advances have occurred, with transgenic plants from several laboratories being prepared for field trails.

A genotype-by-sequencing-single nucleotide polymorphism based linkage map and quantitative trait loci (QTL) associated with resistance to Fusarium oxysporum f. sp. niveum race 2 identified in Citrullus lanatus var. citroides

USDA-ARS?s Scientific Manuscript database

Fusarium wilt, a fungal disease caused by Fusarium oxysporum f. sp. niveum (Fon), devastates watermelon crop production worldwide. Several races, which are differentiated by host range, of the pathogen exist. Resistance to Fon race 2, a particularly virulent strain prevalent in the United States, do...

Rapid and cost-effective method for the detection of the c.533G>A mutation in the HEXA gene.

PubMed

Ribeiro, Diogo; Duarte, Ana Joana; Amaral, Olga

2011-03-01

Tay-Sachs disease is a rare autosomal recessive neurodegenerative disorder that results from mutations in the HEXA gene, leading to β-hexosaminidase A (HexA) α subunit deficiency. An unusual variant of Tay-Sachs disease is known as the B1 variant. Previous studies indicated that, in northern Portugal, this is not only the most common variant but also one of the most prevalent lysosomal storage diseases. Additionally, this variant might also show a higher prevalence in populations of Portuguese and Spanish ancestry. A single mutation is invariably present in at least one of the alleles of B1 variant patients, HEXA mutation c.533G >A. To implement a method for c.533G >A testing in individuals and populations, we have optimized two distinct mutation analysis techniques, one based on restriction fragment length polymorphism analysis and the other based on allelic discrimination. We present the comparison of both methods and their advantages. Mutation screening by allelic discrimination proved to be particularly useful for the studying of large samples of individuals. It is time saving and highly reproducible, and under the conditions used, its cost is lower than the cost of polymerase chain reaction-based restriction fragment length polymorphism analysis.

Comparison of biotyping methods as alternative identification tools to molecular typing of pathogenic Cryptococcus species in sub-Saharan Africa

PubMed Central

Nyazika, Tinashe K.; Robertson, Valerie J.; Nherera, Brenda; Mapondera, Prichard T.; Meis, Jacques F.; Hagen, Ferry

2015-01-01

Summary Cryptococcal meningitis is the leading fungal infection and AIDS defining opportunistic illness in patients with late stage HIV infection, particularly in South-East Asia and sub-Saharan Africa. Given the high mortality, clinical differences and the extensive ecological niche of Cryptococcus neoformans and Cryptococcus gattii species complexes, there is need for laboratories in sub-Sahara African countries to adopt new and alternative reliable diagnostic algorithms that rapidly identify and distinguish these species. We biotyped 74 and then amplified fragment length polymorphism (AFLP) genotyped 66 Cryptococcus isolates from a cohort of patients with HIV-associated cryptococcal meningitis. Cryptococcus gattii sensu lato was isolated at a prevalence of 16.7% (n = 11/66) and C. neoformans sensu stricto was responsible for 83.3% (n = 55/66) of the infections. l-Canavanine glycine bromothymol blue, yeast-carbon-base-d-proline-d-tryptophan and creatinine dextrose bromothymol blue thymine were able to distinguish pathogenic C. gattii sensu lato from C. neoformans sensu stricto species when compared with amplified fragment length polymorphism genotyping. This study demonstrates high C. gattii sensu lato prevalence in Zimbabwe. In addition, biotyping methods can be used as alternative diagnostic tools to molecular typing in resource-limited areas for differentiating pathogenic Cryptococcus species. PMID:26661484

Seroprevalence of East Coast fever in Central Equatoria State, South Sudan.

PubMed

Marcellino, Wani L; Salih, Diaeldin A; Julla, Ibrahim I; El Hussein, Abdel Rahim M

2012-01-01

A cross-sectional survey was conducted in 2005 in different cattle camps in Juba, Mangalla and Terekeka localities of Central Equatoria State, South Sudan. Serum samples were collected from 514 cattle of different age groups. Samples were analysed using an indirect enzyme-linked immunosorbent assay (ELISA) with commercially available polymorphic immunodominant molecule (PIM) ELISA kits. The overall serological prevalence of Theileria parva was 70.8% (364/514). The highest rate of prevalence was observed in Mangalla (91.2%) and the lowest in Juba (61.8%), with Terekeka recording 71.8%. Regarding the age groups, older cattle (over four years of age) showed a significantly higher rate of prevalence (p>0.001) than calves (below one year of age). The implications of these results in the overall epidemiology of East Coast fever in South Sudan are discussed and possible recommendations for future implementation of disease control measures are outlined.

A novel haplotype of spinocerebellar ataxia type 6 contributes to the highest prevalence in western Japan.

PubMed

Terasawa, Hideo; Oda, Masaya; Morino, Hiroyuki; Miyachi, Takafumi; Izumi, Yuishin; Maruyama, Hirofumi; Matsumoto, Masayasu; Kawakami, Hideshi

2004-03-25

The highest prevalence rate of spinocerebellar ataxia type 6 (SCA6) in the worldwide population is in the Chugoku and Kansai areas of Western Japan, but the reason of this geographic characteristics is unclear. We investigated the predisposing haplotypes and their geographic distribution. Genotyping of five microsatellite markers and three single nucleotide polymorphisms linked to the CACNA1A gene in 150 Japanese SCA6 patients from unrelated 118 families revealed three major haplotypes, carrying a pool of one common haplotype core. A founder chromosome was thought to have historically diverged into at least three types. One of the major haplotypes newly identified showed a strong geographical cluster around the Seto Inland Sea in the Chugoku and Kansai areas of Western Japan, whereas the others were widely distributed throughout Japan. The distribution of predisposing haplotypes contributes to the geographical differences in prevalence of SCA6.

Genomic Epidemiology of Salmonella enterica Serotype Enteritidis based on Population Structure of Prevalent Lineages

PubMed Central

Desai, Prerak T.; den Bakker, Henk C.; Mikoleit, Matthew; Tolar, Beth; Trees, Eija; Hendriksen, Rene S.; Frye, Jonathan G.; Porwollik, Steffen; Weimer, Bart C.; Wiedmann, Martin; Weinstock, George M.; Fields, Patricia I.; McClelland, Michael

2014-01-01

Salmonella enterica serotype Enteritidis is one of the most commonly reported causes of human salmonellosis. Its low genetic diversity, measured by fingerprinting methods, has made subtyping a challenge. We used whole-genome sequencing to characterize 125 S. enterica Enteritidis and 3 S. enterica serotype Nitra strains. Single-nucleotide polymorphisms were filtered to identify 4,887 reliable loci that distinguished all isolates from each other. Our whole-genome single-nucleotide polymorphism typing approach was robust for S. enterica Enteritidis subtyping with combined data for different strains from 2 different sequencing platforms. Five major genetic lineages were recognized, which revealed possible patterns of geographic and epidemiologic distribution. Analyses on the population dynamics and evolutionary history estimated that major lineages emerged during the 17th–18th centuries and diversified during the 1920s and 1950s. PMID:25147968

New Mycobacterium tuberculosis Complex Sublineage, Brazzaville, Congo

PubMed Central

Malm, Sven; Linguissi, Laure S. Ghoma; Tekwu, Emmanuel M.; Vouvoungui, Jeannhey C.; Kohl, Thomas A.; Beckert, Patrick; Sidibe, Anissa; Rüsch-Gerdes, Sabine; Madzou-Laboum, Igor K.; Kwedi, Sylvie; Penlap Beng, Véronique; Frank, Matthias; Ntoumi, Francine

2017-01-01

Tuberculosis is a leading cause of illness and death in Congo. No data are available about the population structure and transmission dynamics of the Mycobacterium tuberculosis complex strains prevalent in this central Africa country. On the basis of single-nucleotide polymorphisms detected by whole-genome sequencing, we phylogenetically characterized 74 MTBC isolates from Brazzaville, the capital of Congo. The diversity of the study population was high; most strains belonged to the Euro-American lineage, which split into Latin American Mediterranean, Uganda I, Uganda II, Haarlem, X type, and a new dominant sublineage named Congo type (n = 26). Thirty strains were grouped in 5 clusters (each within 12 single-nucleotide polymorphisms), from which 23 belonged to the Congo type. High cluster rates and low genomic diversity indicate recent emergence and transmission of the Congo type, a new Euro-American sublineage of MTBC. PMID:28221129

New Mycobacterium tuberculosis Complex Sublineage, Brazzaville, Congo.

PubMed

Malm, Sven; Linguissi, Laure S Ghoma; Tekwu, Emmanuel M; Vouvoungui, Jeannhey C; Kohl, Thomas A; Beckert, Patrick; Sidibe, Anissa; Rüsch-Gerdes, Sabine; Madzou-Laboum, Igor K; Kwedi, Sylvie; Penlap Beng, Véronique; Frank, Matthias; Ntoumi, Francine; Niemann, Stefan

2017-03-01

Tuberculosis is a leading cause of illness and death in Congo. No data are available about the population structure and transmission dynamics of the Mycobacterium tuberculosis complex strains prevalent in this central Africa country. On the basis of single-nucleotide polymorphisms detected by whole-genome sequencing, we phylogenetically characterized 74 MTBC isolates from Brazzaville, the capital of Congo. The diversity of the study population was high; most strains belonged to the Euro-American lineage, which split into Latin American Mediterranean, Uganda I, Uganda II, Haarlem, X type, and a new dominant sublineage named Congo type (n = 26). Thirty strains were grouped in 5 clusters (each within 12 single-nucleotide polymorphisms), from which 23 belonged to the Congo type. High cluster rates and low genomic diversity indicate recent emergence and transmission of the Congo type, a new Euro-American sublineage of MTBC.

Prevalence, Patterns, and Genetic Association Analysis of Modic Vertebral Endplate Changes

PubMed Central

Kanna, Rishi Mugesh; Rajagopalan, Veera Ranjani; Natesan, Senthil; Muthuraja, Raveendran; Cheung, Kenneth Man Chee; Chan, Danny; Kao, Patrick Yu Ping; Yee, Anita; Shetty, Ajoy Prasad

2017-01-01

Study Design A prospective genetic association study. Purpose The etiology of Modic changes (MCs) is unclear. Recently, the role of genetic factors in the etiology of MCs has been evaluated. However, studies with a larger patient subset are lacking, and candidate genes involved in other disc degeneration phenotypes have not been evaluated. We studied the prevalence of MCs and genetic association of 41 candidate genes in a large Indian cohort. Overview of Literature MCs are vertebral endplate signal changes predominantly observed in the lumbar spine. A significant association between MCs and lumbar disc degeneration and nonspecific low back pain has been described, with the etiopathogenesis implicating various mechanical, infective, and biochemical factors. Methods We studied 809 patients using 1.5-T magnetic resonance imaging to determine the prevalence, patterns, distribution, and type of lumbar MCs. Genetic association analysis of 71 single nucleotide polymorphisms (SNPs) of 41 candidate genes was performed based on the presence or absence of MCs. SNPs were genotyped using the Sequenome platform, and an association test was performed using PLINK software. Results The mean age of the study population (n=809) was 36.7±10.8 years. Based on the presence of MCs, the cohort was divided into 702 controls and 107 cases (prevalence, 13%). MCs were more commonly present in the lower (149/251, 59.4%) than in the upper (102/251, 40.6%) endplates. L4–5 endplates were the most commonly affected levels (30.7%). Type 2 MCs were the most commonly observed pattern (n=206, 82%). The rs2228570 SNP of VDR (p=0.02) and rs17099008 SNP of MMP20 (p=0.03) were significantly associated with MCs. Conclusions Genetic polymorphisms of SNPs of VDR and MMP20 were significantly associated with MCs. Understanding the etiopathogenetic mechanisms of MCs is important for planning preventive and therapeutic strategies. PMID:28874978

Genetic variants of APOC3 promoter and HLA-B genes in an HIV infected cohort in northern South Africa: a pilot study.

PubMed

Masebe, Tracy; Bessong, Pascal Obong; Ndip, Roland Ndip; Meyer, Debra

2014-06-26

Metabolic disorders and hypersensitivities affect tolerability and impact adherence to highly active antiretroviral therapy (HAART). The aim of this study was to determine the prevalence of C-482T/T-455C variants in the Apolipoprotein C3 (APOC3) promoter gene and Human leukocyte antigen (HLA)-B*57:01, known to impact lipid metabolic disorders and hypersensitivity respectively; and to correlate genotypes with gender, CD4+ cell count and viral load in an HIV infected cohort in northern South Africa. Frequencies of C-482 and T-455 polymorphisms in APOC3 were determined by restriction fragment length polymorphism analysis. Allele determination for HLA-B was performed with Assign SBT software in an HLA library. Analysis of APOC3 C-482 site revealed a prevalence of 196/199 (98.5%) for CC, 1/199 (0.5%) for CT and 2/199 (1.0%) for TT genotype (p = 0.000 with 1° of freedom; χ2 = 126.551). For the T-455 site, prevalences were: 69/199 (35%) for TT and 130/199 (65%) for the CC genotype (p = 0.000 with 1° of freedom; χ2 = 199). There was no association between gender and the presence of -482 (p = 1; χ2 = 0.00001) or -455 genotypes (p = 0.1628; χ2 = 1.9842). There was no significant difference in the increase in CD4+ cell count irrespective of genotypes. Significant increases in CD4+ cell count were observed in males and females considering the -455C genotype, but not in males for the -455T genotype. Viral load decreases were significant with the -455C and -482C genotypes irrespective of gender. HLA-B*57:01 was not identified in the study cohort. The apparently high prevalence of APOC3 T-455CC genotype needs confirmation with a larger samples size and triglyceride measurements to support screening of patients to pre-empt HAART associated lipid disorders.

Lyme disease risk not amplified in a species-poor vertebrate community: similar Borrelia burgdorferi tick infection prevalence and OspC genotype frequencies.

PubMed

States, S L; Brinkerhoff, R J; Carpi, G; Steeves, T K; Folsom-O'Keefe, C; DeVeaux, M; Diuk-Wasser, M A

2014-10-01

The effect of biodiversity declines on human health is currently debated, but empirical assessments are lacking. Lyme disease provides a model system to assess relationships between biodiversity and human disease because the etiologic agent, Borrelia burgdorferi, is transmitted in the United States by the generalist black-legged tick (Ixodes scapularis) among a wide range of mammalian and avian hosts. The 'dilution effect' hypothesis predicts that species-poor host communities dominated by white-footed mice (Peromyscus leucopus) will pose the greatest human risk because P. leucopus infects the largest numbers of ticks, resulting in higher human exposure to infected I. scapularis ticks. P. leucopus-dominated communities are also expected to maintain a higher frequency of those B. burgdorferi outer surface protein C (ospC) genotypes that this host species more efficiently transmits ('multiple niche polymorphism' hypothesis). Because some of these genotypes are human invasive, an additive increase in human disease risk is expected in species-poor settings. We assessed these theoretical predictions by comparing I. scapularis nymphal infection prevalence, density of infected nymphs and B. burgdorferi genotype diversity at sites on Block Island, RI, where P. leucopus dominates the mammalian host community, to species-diverse sites in northeastern Connecticut. We found no support for the dilution effect hypothesis; B. burgdorferi nymphal infection prevalence was similar between island and mainland and the density of B. burgdorferi infected nymphs was higher on the mainland, contrary to what is predicted by the dilution effect hypothesis. Evidence for the multiple niche polymorphism hypothesis was mixed: there was lower ospC genotype diversity at island than mainland sites, but no overrepresentation of genotypes with higher fitness in P. leucopus or that are more invasive in humans. We conclude that other mechanisms explain similar nymphal infection prevalence in both communities and that high ospC genotype diversity can be maintained in both species-poor and species-rich communities. Copyright © 2014 Elsevier B.V. All rights reserved.

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

R353Q polymorphism in the factor VII gene and cardiovascular risk in Heterozygous Familial Hypercholesterolemia: a case-control study.

PubMed

Criado-García, Juan; Fuentes, Francisco; Cruz-Teno, Cristina; García-Rios, Antonio; Jiménez-Morales, Anabel; Delgado-Lista, Javier; Mata, Pedro; Alonso, Rodrigo; López-Miranda, José; Pérez-Jiménez, Francisco

2011-04-09

Heterozygous Familial Hypercholesterolemia (FH) is a genetic disorder characterized by a high risk of cardiovascular disease. Certain polymorphisms of the factor VII gene have been associated with the development of coronary artery disease and there is a known association between factor VII levels and polymorphic variants in this gene. To date, no study has evaluated the association between factor VII and coronary artery disease in patients with FH. This case-control study comprised 720 patients (546 with FH and 174 controls). We determined the prevalence and allele frequencies of the R353Q polymorphism of factor VII, the plasma levels of factor VII antigen (FVII Ag) and whether they could be predictive factors for cardiovascular risk. 75% (410) of the patients with FH were RR, 23% (127) RQ and 1.6% (9) QQ; in the control group 75.3% (131) were RR, 21.3% (37) RQ and 3.4% (6) QQ (p = 0.32). No statistically significant associations were observed in the distribution of genotypes and allele frequencies between case (FH) and control groups. Nor did we find differences when we evaluated the relationship between the R353Q polymorphism and cardiovascular risk (including coronary disease, ischemic stroke and peripheral arterial disease), either in the univariate analysis or after adjustment for sex, age, arterial hypertension, body mass index, xanthomas, diabetes, smoking, HDLc and LDLc and lipid-lowering treatment. The FVII Ag concentrations behaved in a similar fashion, with no differences for the interaction between controls and those with FH (RR vs. RQ/QQ; p = 0.96). In the subgroup of patients with FH no association was found among cardiovascular disease, genotype and FVII Ag levels (RR vs. RQ/QQ; p = 0.97). Our study did not find a direct relationship between cardiovascular risk in patients with Heterozygous Familial Hypercholesterolemia, the R353Q polymorphism of factor VII and FVII Ag levels.

Study of β2-Glycoprotein I Polymorphisms in Patients With Chronic Renal Failure as a Predisposing Factor for the Development of Anti-β2-Glycoprotein I Auto-Antibodies.

PubMed

Serrano, M; Cabrera-Marante, O; Martínez-Flores, J A; Morales, P; Pérez, D; Mora, S; García, F; González, E; Paz-Artal, E; Morales, J M; Serrano, A

2016-11-01

Immunoglobulin (Ig)A anti-β 2 -glycoprotein I (aB2GP1) antibodies are associated with thrombotic events, cardiovascular morbidity, and death in dialysis patients. About 30% of patients with chronic renal disease are positive for IgA aB2GP1; however, the origin of these antibodies is unknown. It has been speculated that dialysis membranes, age, or etiology of renal base disease are possible precipitating factors, although these factors do not appear to be the source of antibodies. B2GP1 is a protein of 326 amino acids grouped into five domains. Eight polymorphisms have been described; the most important are Val/Leu 247 , which appears to predispose aB2GP1 antibody production in patients with anti-phospholipid syndrome, and Trp/Ser 316 , which appears to have protective antibody production of aB2GP1. DNA samples from 92 patients with renal failure on hemodialysis were randomly collected with a 1:1 ratio for the positivity for IgA aB2GP1. Forty-six samples were positive for IgA aB2GP1 (group 1) and 46 negative for IgA aB2GP1 (group 2). All samples were anonymized to study polymorphism Val/Leu 247 and polymorphism Trp/Ser 316 . No significant differences were observed between those who were positive or negative for IgA aB2GP1 in patients with renal failure treated with hemodialysis and the polymorphism located in codons 247 and 316. The two groups of patients have the same prevalence in polymorphisms 247 and 316, and therefore there appears not to be a genetic predisposition in our population. New trigger factors must be studied. Copyright © 2016 Elsevier Inc. All rights reserved.

Association analysis of FAS-670A/G and FASL-844C/T polymorphisms with risk of generalized aggressive periodontitis disease.

PubMed

Asgari, Rezvan; Yari, Kheirollah; Mansouri, Kamran; Bakhtiari, Mitra

2018-04-01

The interaction of FAS/FAS ligand (FASL) serves an important role in the upregulation of apoptotic processes through different mechanisms in cells. Previous studies have established that the polymorphisms FAS -670A/G and FASL -844C/T are associated with risk of generalized aggressive periodontitis (GAP) in different ethnic populations. Therefore, in the present study, it was investigated for the first time whether FAS -670A/G and FASL -844C/T polymorphisms were associated with risk of GAP in Iran. This case-control study performed the polymerase chain reaction-restriction fragment length polymorphism method in 25 patients with GAP and 110 normal subjects as controls. The results indicated that there was no significant difference in FAS -670A/G genotype frequency between the GAP and control groups. A higher frequency of the combined genotype (AG+GG) was observed in the GAP patients (96.0%) compared with the control subjects (90.9%), though this was not significant [χ 2 =0.705, degrees of freedom (df)=1, P=0.401]. Similarly, the prevalence of the G allele was non-significantly higher in the GAP group (62.0%) compared with that in the controls (60.0%; χ 2 =0.012, df=1, P=0.913). For FASL-844C/T polymorphism, the frequency of the combined genotype (CT+TT) was higher in the GAP group (96.0%) when compared with the control subjects (91.8%); however its association was not statistically significant (χ 2 =0.519, df=1, P=0.471). The frequency of the T allele only marginally differed between the groups, being 60.0% in the GAP group and 50.9% in the controls (χ 2 =3.627, df=1, P=0.057). These results indicated that there were no significant associations between the FAS -670A/G and FASL -844C/T polymorphisms and the risk of disease in GAP patients when compared with normal individuals.

R353Q polymorphism in the factor VII gene and cardiovascular risk in Heterozygous Familial Hypercholesterolemia: a case-control study

PubMed Central

2011-01-01

Background Heterozygous Familial Hypercholesterolemia (FH) is a genetic disorder characterized by a high risk of cardiovascular disease. Certain polymorphisms of the factor VII gene have been associated with the development of coronary artery disease and there is a known association between factor VII levels and polymorphic variants in this gene. To date, no study has evaluated the association between factor VII and coronary artery disease in patients with FH. Results This case-control study comprised 720 patients (546 with FH and 174 controls). We determined the prevalence and allele frequencies of the R353Q polymorphism of factor VII, the plasma levels of factor VII antigen (FVII Ag) and whether they could be predictive factors for cardiovascular risk. 75% (410) of the patients with FH were RR, 23% (127) RQ and 1.6% (9) QQ; in the control group 75.3% (131) were RR, 21.3% (37) RQ and 3.4% (6) QQ (p = 0.32). No statistically significant associations were observed in the distribution of genotypes and allele frequencies between case (FH) and control groups. Nor did we find differences when we evaluated the relationship between the R353Q polymorphism and cardiovascular risk (including coronary disease, ischemic stroke and peripheral arterial disease), either in the univariate analysis or after adjustment for sex, age, arterial hypertension, body mass index, xanthomas, diabetes, smoking, HDLc and LDLc and lipid-lowering treatment. The FVII Ag concentrations behaved in a similar fashion, with no differences for the interaction between controls and those with FH (RR vs. RQ/QQ; p = 0.96). In the subgroup of patients with FH no association was found among cardiovascular disease, genotype and FVII Ag levels (RR vs. RQ/QQ; p = 0.97). Conclusions Our study did not find a direct relationship between cardiovascular risk in patients with Heterozygous Familial Hypercholesterolemia, the R353Q polymorphism of factor VII and FVII Ag levels. PMID:21477332

Correlations of CTLA-4 gene polymorphisms and hepatitis C chronic infection.

PubMed

Danilovic, Debora L S; Mendes-Correa, Maria C; Lima, Erika U; Zambrini, Heverton; K Barros, Raffaelle; Marui, Suemi

2012-05-01

Cytotoxic T lymphocyte-associated factor 4 (CTLA-4) functions as a negative regulator of T cell-mediated immune response. Molecular changes associated to CTLA-4 gene polymorphisms could reduce its ability to suppress and control lymphocyte proliferation. To evaluate the frequency of CTLA-4 gene polymorphisms in chronic hepatitis C virus (HCV) infected patients and correlate to clinical and histological findings. We evaluated 112 HCV-infected subjects prospectively selected and 183 healthy controls. Clinical and liver histological data were analysed. -318C > T, A49G and CT60 CTLA-4 single-nucleotide polymorphisms (SNPs) were studied by PCR-RFLP and AT(n) polymorphism by DNA fragment analysis by capillary electrophoresis in automatic sequencer. Eight AT repetitions in 3'UTR region were more frequent in HCV-infected subjects. We found a positive association of -318C and + 49G with HCV genotype 3 (P = 0.008, OR 9.13, P = 0.004, OR 2.49 respectively) and an inverse association of both alleles with HCV genotype 1 (P = 0.020, OR 0.19, P = 0.002, OR 0.38 respectively). Allele + 49G was also associated to aminotransferases quotients > 3 (qALT, P = 0.034, qAST, P = 0.041). Allele G of CT60 SNP was also associated with qAST > 3 (P = 0.012). Increased number of AT repetitions was positively associated to severe necroinflammatory activity scores in liver biopsies (P = 0.045, OR 4.62). CTLA-4 gene polymorphisms were associated to HCV-infection. Eight AT repetitions were more prevalent in HCV-infected subjects. -318C and + 49G alleles were associated to genotypes 1 and 3 infections and increased number of AT repetitions in 3'UTR region favoured severe necroinflammatory activity scores in liver biopsies. © 2011 John Wiley & Sons A/S.

Polymorphisms in dopaminergic system genes; association with criminal behavior and self-reported aggression in violent prison inmates from Pakistan.

PubMed

Qadeer, Muhammad Imran; Amar, Ali; Mann, J John; Hasnain, Shahida

2017-01-01

Genetic factors contribute to antisocial and criminal behavior. Dopamine transporter DAT-1 (SLC6A3) and DRD2 gene for the dopamine-2 receptor are dopaminergic system genes that regulate dopamine reuptake and signaling, and may be part of the pathogenesis of psychiatric disorders including antisocial behaviors and traits. No previous studies have analyzed DAT-1 and DRD2 polymorphisms in convicted murderers, particularly from Indian subcontinent. In this study we investigated the association of 40 bp VNTR polymorphism of DAT-1 and Taq1 variant of DRD2 gene (rs1800479) with criminal behavior and self-reported aggression in 729 subjects, including 370 men in Pakistani prisons convicted of first degree murder(s) and 359 control men without any history of violence or criminal tendency. The 9R allele of DAT-1 VNTR polymorphism was more prevalent in convicted murderers compared with control samples, for either one or two risk alleles (OR = 1.49 and 3.99 respectively, P = 0.003). This potential association of DAT-1 9R allele polymorphism with murderer phenotype was confirmed assuming different genetic models of inheritance. However, no genetic association was found for DRD2 Taq1 polymorphism. In addition, a combined haplotype (9R-A2) of DAT-1 and DRD2 genes was associated with this murderer phenotype. Further, 9R allele of DAT-1 was also associated with response to verbal abuse and parental marital complications, but not with other measures pertinent to self-reported aggression. These results suggest that 9R allele, which may influence levels of intra-synaptic dopamine in the brain, may contribute to criminal tendency in this sample of violent murderers of Pakistani origin. Future studies are needed to replicate this finding in other populations of murderers and see if this finding extends to other forms of violence and lesser degrees of aggression.

Polymorphisms in dopaminergic system genes; association with criminal behavior and self-reported aggression in violent prison inmates from Pakistan

PubMed Central

Qadeer, Muhammad Imran; Amar, Ali; Mann, J. John; Hasnain, Shahida

2017-01-01

Genetic factors contribute to antisocial and criminal behavior. Dopamine transporter DAT-1 (SLC6A3) and DRD2 gene for the dopamine-2 receptor are dopaminergic system genes that regulate dopamine reuptake and signaling, and may be part of the pathogenesis of psychiatric disorders including antisocial behaviors and traits. No previous studies have analyzed DAT-1 and DRD2 polymorphisms in convicted murderers, particularly from Indian subcontinent. In this study we investigated the association of 40 bp VNTR polymorphism of DAT-1 and Taq1 variant of DRD2 gene (rs1800479) with criminal behavior and self-reported aggression in 729 subjects, including 370 men in Pakistani prisons convicted of first degree murder(s) and 359 control men without any history of violence or criminal tendency. The 9R allele of DAT-1 VNTR polymorphism was more prevalent in convicted murderers compared with control samples, for either one or two risk alleles (OR = 1.49 and 3.99 respectively, P = 0.003). This potential association of DAT-1 9R allele polymorphism with murderer phenotype was confirmed assuming different genetic models of inheritance. However, no genetic association was found for DRD2 Taq1 polymorphism. In addition, a combined haplotype (9R-A2) of DAT-1 and DRD2 genes was associated with this murderer phenotype. Further, 9R allele of DAT-1 was also associated with response to verbal abuse and parental marital complications, but not with other measures pertinent to self-reported aggression. These results suggest that 9R allele, which may influence levels of intra-synaptic dopamine in the brain, may contribute to criminal tendency in this sample of violent murderers of Pakistani origin. Future studies are needed to replicate this finding in other populations of murderers and see if this finding extends to other forms of violence and lesser degrees of aggression. PMID:28582390

Differences in UGT1A1, UGT1A7, and UGT1A9 polymorphisms between Uzbek and Japanese populations.

PubMed

Maeda, Hiromichi; Hazama, Shoichi; Shavkat, Abdiev; Okamoto, Ken; Oba, Koji; Sakamoto, Junichi; Takahashi, Kenichi; Oka, Masaki; Nakamura, Daisuke; Tsunedomi, Ryouichi; Okayama, Naoko; Mishima, Hideyuki; Kobayashi, Michiya

2014-06-01

Uridine-diphosphate glucuronosyltransferase 1A (UGT1A) is a key enzyme involved in irinotecan metabolism, and polymorphisms in the UGT1A gene are associated with irinotecan-induced toxicity. The aim of this study was to elucidate the allele frequencies of UGT1A polymorphisms in healthy Uzbek volunteers, and to compare them with those of the Japanese population. A total of 97 healthy volunteers from Uzbekistan were enrolled and blood samples were collected from each participant. Genotyping analysis was performed by fragment size analysis for UGT1A1*28, direct sequencing for UGT1A7*3 and UGT1A9*22, and TaqMan assays for UGT1A1*93, UGT1A1*6, UGT1A1*27, UGT1A1*60, and UGT1A7*12. The frequencies of polymorphisms were compared with the Japanese population by using the data previously reported from our study group. When the Uzbek and Japanese populations were compared, heterozygotes or homozygotes for UGT1A1*28, UGT1A1*60, and UGT1A1*93 were significantly more frequent in the Uzbek population (P < 0.01). The rate of UGT1A7*12 was not significantly different between the two populations, whereas UGT1A1*6 and UGT1A9*22 were significantly less frequent in the Uzbek population (P < 0.05). UGT1A7*1 were less prevalent in the Uzbek population than in the Japanese population (P < 0.01). The Uzbek population has different frequencies of polymorphisms in UGT1A genes compared with the Japanese population. A comprehensive study of the influence of UGT1A1 polymorphisms on the risk of irinotecan-induced toxicity is necessary for optimal use of irinotecan treatment.

Methylenetetrahydrofolate reductase gene polymorphisms and risk of acute lymphoblastic leukemia in children.

PubMed

Sadananda Adiga, M N; Chandy, S; Ramachandra, N; Appaji, L; Aruna Kumari, B S; Ramaswamy, G; Savithri, H S; Krishnamoorthy, L

2010-01-01

Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism and is involved in DNA synthesis, DNA repair and DNA methylation. Genetic polymorphisms of this enzyme have been shown to impact several diseases, including cancer. Leukemias are malignancies arising from rapidly proliferating hematopoietic cells having great requirement of DNA synthesis. This case-control study was undertaken to analyze the association of the MTHFR gene polymorphisms 677 C"T and 1298 A"C and the risk of acute lymphoblastic leukemia in children. Eighty-six patients aged below 15 years with a confirmed diagnosis of acute lymphoblastic leukemia (ALL) and 99 matched controls were taken for this study. Analysis of the polymorphisms was done using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Frequency of MTHFR 677 CC and CT were 85.9% and 14.1% in the controls, and 84.9% and 15.1% in the cases. The 'T' allele frequency was 7% and 7.5% in cases and controls respectively. The frequency of MTHFR 1298 AA, AC, and CC were 28.3%, 55.6% and 16.1% for controls and 23.3%, 59.3% and 17.4% for cases respectively. The 'C' allele frequency for 1298 A-->C was 43.9% and 47% respectively for controls and cases. The odds ratio (OR) for C677T was 1.08 (95% CI 0.48-2.45, p = 0.851) and OR for A1298C was 1.29 (95% CI 0.65-2.29, p = 0.46) and OR for 1298 CC was 1.31 (95% CI 0.53-3.26, p = 0.56). The OR for the combined heterozygous status (677 CT and 1298 AC) was 1.94 (95% CI 0.58-6.52, p = 0.286). The prevalence of 'T' allele for 677 MTHFR polymorphism was low in the population studied. There was no association between MTHFR 677 C-->T and 1298 A-->C gene polymorphisms and risk of ALL, which may be due to the small sample size.

Genetic variations in toll-like receptor 4 in Mexican-Mestizo patients with intra-abdominal infection and/or pneumonia.

PubMed

Rodriguez-Osorio, Carlos A; Lima, Guadalupe; Herrera-Caceres, Jaime O; Villegas-Torres, Beatriz E; Zuñiga, Joaquin; Ponce-de-Leon, Sergio; Llorente, Luis; Sifuentes-Osornio, Jose

2013-06-01

Sepsis is a leading cause of death around the world, and 73-83% of all sepsis cases requiring attention in intensive care units are linked to intra-abdominal infection (IAI) or pneumonia. The activation of innate immunity is central to the manifestation of sepsis, and toll-like receptor (TLR) 4 plays an important role in this activation process. The 299G and 399I alleles of TLR4 have been linked with an increased risk of Gram-negative bacteria (GNB) infections and septic shock in some populations. This case-control study evaluated the prevalence of D299G/T399I polymorphisms in Mexican patients with IAI and/or pneumonia and in healthy controls. Genotyping revealed that 1 in 44 patients (2.3%; CI 95%: 0.05-12.0%) and 4 in 126 controls (3.2%; CI 95%: 0.9-7.9%) were heterozygous for both the D299G and T399l polymorphisms (OR: 0.71, CI 95%: 0.01-7.44, p = NS), confirming the co-segregation of these alleles in this population. Furthermore, the patients with a GNB infection and severe sepsis were not carriers of the risk alleles. In summary, this report shows that the frequency of the D299G and T399I polymorphisms in Mexican-Mestizos is lower than anticipated in comparison with other ethnic groups, emphasizing the variable distribution of TLR4 polymorphisms among different populations. Consequently, this study was not able to detect associations between TLR4 polymorphisms and sepsis in this population. Copyright © 2013 Elsevier B.V. All rights reserved.

UCP1 -3826 A>G polymorphism affects weight, fat mass, and risk of type 2 diabetes mellitus in grade III obese patients.

PubMed

Nicoletti, Carolina Ferreira; de Oliveira, Ana Paula Rus Perez; Brochado, Maria Jose Franco; de Oliveira, Bruno Parenti; Pinhel, Marcela Augusta de Souza; Marchini, Julio Sergio; dos Santos, Jose Ernesto; Salgado Junior, Wilson; Silva Junior, Wilson Araujo; Nonino, Carla Barbosa

2016-01-01

We investigated whether or not the UCP1 -3826 A>G polymorphism is associated with obesity and related metabolic disorders in grade III obese patients. 150 obese patients (body mass index ≥35 kg/m(2)) who were candidates for bariatric surgery were studied. Weight (kg), body mass index (kg/m(2)); fat free mass (kg), fat mass (kg), energy intake (kcal), level of physical activity, plasma levels of glucose, total cholesterol, low-density lipoprotein, high-density lipoprotein (HDL), triacylglycerols, and the prevalence of comorbidities associated with obesity were collected from medical records. Polymorphism rs1800592 genotyping was performed through allelic discrimination method in real time polymerase chain reaction using the TaqMan predesigned SNP Genotyping Assays kits. The t test was done to determine if genotypes of each polymorphism are associated with anthropometric and body composition variables. Linear regression models were used for age, sex, height, physical activity, and energy intake in weight and body composition variations (P < 0.05). Among these 150 individuals (47.2 ± 10.5 y, 80% women) the distribution of AA, AG, and GG was 41.3%, 45.3%, and 13.4%, respectively. Weight and body fat were lower in individuals who were carriers of a mutated allele G. It was observed that mutated homozygotes (GG) had a lower frequency of type 2 diabetes mellitus compared with those of wild allele (AA+AG). UCP1 -3826 A>G polymorphism is associated with weight, body fat mass, and risk of type 2 diabetes mellitus in obese individuals candidates for bariatric surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

Limited artemisinin resistance-associated polymorphisms in Plasmodium falciparum K13-propeller and PfATPase6 gene isolated from Bioko Island, Equatorial Guinea

PubMed Central

Li, Jian; Chen, Jiangtao; Xie, Dongde; Eyi, Urbano Monsuy; Matesa, Rocio Apicante; Ondo Obono, Maximo Miko; Ehapo, Carlos Sala; Yang, Liye; Yang, Huitian; Lin, Min

2016-01-01

Objective With emergence and geographically expanding of antimalarial resistance worldwide, molecular markers are essential tool for surveillance of resistant Plasmodium parasites. Recently, single-nucleotide polymorphisms (SNPs) in the PF3D7_1343700 kelch propeller (K13-propeller) domain are shown to be associated with artemisinin (ART) resistance in vivo and in vitro. This study aims to investigate the ART resistance-associated polymorphisms of K13-propeller and PfATPase6 genes in Plasmodium falciparum isolates from Bioko Island, Equatorial Guinea (EG). Methods A total of 172 samples were collected from falciparum malaria patients on Bioko Island between 2013 and 2014. The polymorphisms of K13-propeller and PfATPase6 genes were analyzed by Nest-PCR and sequencing. Results Sequences of K13-propeller and PfATPase6 were obtained from 90.74% (98/108) and 91.45% (139/152) samples, respectively. The 2.04% (2/98) cases had non-synonymous K13-propeller A578S mutation but no found the mutations associated with ART resistance in Southeast Asia. For PfATPase6, the mutations were found at positions N569K and A630S with the mutation prevalence of 7.91% (11/139) and 1.44% (2/139), respectively. In addition, a sample with the mixed type at position I723V was discovered (0.72%, 1/139). Conclusions This study initially offers an insight of K13-propeller and PfATPase6 polymorphisms on Bioko Island, EG. It suggests no widespread ART resistance or tolerance in the region, and might be helpful for developing and updating guidance for the use of ART-based combination therapies (ACTs). PMID:27054064

Limited artemisinin resistance-associated polymorphisms in Plasmodium falciparum K13-propeller and PfATPase6 gene isolated from Bioko Island, Equatorial Guinea.

PubMed

Li, Jian; Chen, Jiangtao; Xie, Dongde; Eyi, Urbano Monsuy; Matesa, Rocio Apicante; Ondo Obono, Maximo Miko; Ehapo, Carlos Sala; Yang, Liye; Yang, Huitian; Lin, Min

2016-04-01

With emergence and geographically expanding of antimalarial resistance worldwide, molecular markers are essential tool for surveillance of resistant Plasmodium parasites. Recently, single-nucleotide polymorphisms (SNPs) in the PF3D7_1343700 kelch propeller (K13-propeller) domain are shown to be associated with artemisinin (ART) resistance in vivo and in vitro. This study aims to investigate the ART resistance-associated polymorphisms of K13-propeller and PfATPase6 genes in Plasmodium falciparum isolates from Bioko Island, Equatorial Guinea (EG). A total of 172 samples were collected from falciparum malaria patients on Bioko Island between 2013 and 2014. The polymorphisms of K13-propeller and PfATPase6 genes were analyzed by Nest-PCR and sequencing. Sequences of K13-propeller and PfATPase6 were obtained from 90.74% (98/108) and 91.45% (139/152) samples, respectively. The 2.04% (2/98) cases had non-synonymous K13-propeller A578S mutation but no found the mutations associated with ART resistance in Southeast Asia. For PfATPase6, the mutations were found at positions N569K and A630S with the mutation prevalence of 7.91% (11/139) and 1.44% (2/139), respectively. In addition, a sample with the mixed type at position I723V was discovered (0.72%, 1/139). This study initially offers an insight of K13-propeller and PfATPase6 polymorphisms on Bioko Island, EG. It suggests no widespread ART resistance or tolerance in the region, and might be helpful for developing and updating guidance for the use of ART-based combination therapies (ACTs).

Association of catalase gene polymorphisms with catalase activity and susceptibility to systemic lupus erythematosus in the Suez Canal area, Egypt.

PubMed

Ghaly, M S; Ghattas, M H; Labib, S M

2012-10-01

The present study evaluated the relationship of genetic variants in both promoter (-262 C/T) and in exonic (389 C/T) regions of the catalase (CAT) gene to CAT activity and risk of systemic lupus erythematosus (SLE) in Suez Canal-area patients. CAT gene polymorphisms were assessed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). CAT activity was measured by using a spectrophotometer. We compared the frequencies of CAT 389 C/T and -262 C/T polymorphic variants between SLE patients (n = 103) and healthy controls (n = 103). CAT 389 C/T is associated with SLE susceptibility, with the T allele being significantly more frequent among SLE patients than healthy controls. There was no association, however, between CAT activity and genotypes of 389 C/T. We did not observe significant differences in the prevalence of CAT -262 C/T polymorphic variants in SLE patients and controls, however, we found that patients with the CAT -262 CT and TT genotypes had low CAT activity, and these genotypes showed a significant association with thrombocytopaenia, leukopaenia and the presence of anti-snRNP in SLE patients. In conclusion, the present study supports the notion of in vivo oxidative stress in SLE as indicated by the decrease in CAT activity. The allelic variations in the CAT gene -262 are more likely to affect the expression or the function of the enzyme. Since CAT may be pathogenetically linked to SLE, and owing to its free-radical origin, it appears reasonable to target lipid peroxidation by dietary and/or pharmacological antioxidants.

MBL-2 polymorphisms (codon 54 and Y-221X) and low MBL levels are associated with susceptibility to multi organ dysfunction in P. falciparum malaria in Odisha, India.

PubMed

Das, Bidyut K; Panda, Aditya K

2015-01-01

Mannose binding lectin, a plasma protein protects host from virus, bacteria, and parasites. Deficiency in MBL levels has been associated with susceptibility to various infectious diseases including P. falciparum malaria. Common MBL polymorphisms in promoter and coding regions are associated with decrease in plasma MBL levels or production of deformed MBL, respectively. In the present study, we hypothesized that MBL2 variants and plasma MBL levels could be associated with different clinical phenotypes of severe P. falciparum malaria. A hospital based study was conducted in eastern Odisha, India which is endemic to P. falciparum malaria. Common MBL-2 polymorphisms (codon 54, H-550L, and Y-221X) were typed in 336 cases of severe malaria (SM) [94 cerebral malaria (CM), 120 multi-organ dysfunction (MOD), 122 non-cerebral severe malaria (NCSM)] and 131 un-complicated malaria patients (UM). Plasma MBL levels were quantified by ELISA. Severe malaria patients displayed lower plasma levels of MBL compared to uncomplicated falciparum malaria. Furthermore, on categorization of severe malaria patients into various subtypes, plasma MBL levels were very low in MOD patients compared to other categories. Higher frequency of AB genotype and allele B was observed in MOD compared to UM (AB genotype: P = 0.006; B allele: P = 0.008). In addition, prevalence of YX genotype of MBL Y-221X polymorphism was also statistically more frequent in MOD case than UM (P = 0.009). The observations of the present study reveal that MBL-2 polymorphisms (codon 54 and Y-221X) and lower plasma MBL levels are associated with increased susceptibility to multi organ dysfunctions in P. falciparum malaria.

Resistin polymorphims, plasma resistin levels and obesity in Tunisian volunteers.

PubMed

Zayani, Nesrine; Hamdouni, Haithem; Boumaiza, Imen; Achour, Ons; Neffati, Fadoua; Omezzine, Asma; Najjar, Mohamed Fadhel; Bouslama, Ali

2018-02-01

Adipose tissue is an important endocrine organ that secretes a number of adipokines, like Resistin (RETN); it's an adipocytes-secreted cytokine and has been proposed as a link between obesity and diabetes. Many resistin gene polymorphisms were described and their implication in obesity was controversial. This study was to investigate the prevalence of single nucleotide polymorphisms (SNPs) in RETN gene 420C/G; 44G/A; 62G/A; 394C/G and 299 G/A and their association with Resistin level and obesity in Tunisian volunteers. We recruited 169 nonobese (mean age=42.16-14.26 years; mean body mass index [BMI]=24.51-3.69 kg/m 2 ) and 160 obese (mean age=47.86-11.17 years; mean BMI=36-4.78 kg/m 2 ). Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism. Anthropometric parameters, lipid levels, Glycemia and insulinemia were measured, BMI was calculated and insulinresistance was evaluated with the homeostasis model assessment insulin resistance (HOMA-IR) and resistin level was measured by ELISA. Statistical analyses were performed by SPSS19.0. After adjustment for confounding parameters; the Odds Ratio (OR) of obesity associated with mutated genotypes at 420C/G compared with normal genotype was as: OR=2.17; 95% CI [1.28-3.68], P=.004. The serum Resistin levels present no significant association with all RETN polymorphisms and it was significantly associated with BMI (P=.047). In our haplotype analysis, one haplotype seems to be protective and one other seems to be the highest risk to obesity. The 420 C/G Polymorphism were associated with obesity and Leptin concentration in our population. © 2017 Wiley Periodicals, Inc.

Associations of VEGF-C Genetic Polymorphisms with Urothelial Cell Carcinoma Susceptibility Differ between Smokers and Non-Smokers in Taiwan

PubMed Central

Tung, Min-Che; Hsieh, Ming-Ju; Wang, Shian-Shiang; Yang, Shun-Fa; Chen, Shiou-Sheng; Wang, Shih-Wei; Lee, Liang-Ming; Lee, Wei-Jiunn; Chien, Ming-Hsien

2014-01-01

Background Vascular endothelial growth factor (VEGF)-C is associated with lymphangiogenesis, pelvic regional lymph node metastasis, and an antiapoptotic phenotype in urothelial cell carcinoma (UCC). Knowledge of potential roles of VEGF-C genetic polymorphisms in susceptibility to UCC is lacking. This study was designed to examine associations between VEGF-C gene variants and UCC susceptibility and evaluate whether they are modified by smoking. Methodology/Principal Findings Five single-nucleotide polymorphisms (SNPs) of VEGF-C were analyzed by a TaqMan-based real-time polymerase chain reaction (PCR) in 233 patients with UCC and 520 cancer-free controls. A multivariate logistic regression was applied to model associations between genetic polymorphisms and UCC susceptibility, and to determine if the effect was modified by smoking. We found that after adjusting for other covariates, individuals within the entire population and the 476 non-smokers carrying at least one A allele at VEGF-C rs1485766 respectively had 1.742- and 1.834-fold risks of developing UCC than did wild-type (CC) carriers. Among the 277 smokers, we found that VEGF-C rs7664413 T (CT+TT) and rs2046463 G (AG+GG) allelic carriers were more prevalent in UCC patients than in non-cancer participants. Moreover, UCC patients with the smoking habit who had at least one T allele of VEGF-C rs7664413 were at higher risk of developing larger tumor sizes (p = 0.021), compared to those patients with CC homozygotes. Conclusions Our results suggest that the involvement of VEGF-C genotypes in UCC risk differs among smokers compared to non-smokers among Taiwanese. The genetic polymorphism of VEGF-C rs7664413 might be a predictive factor for the tumor size of UCC patients who have a smoking habit. PMID:24608123

Associations of VEGF-C genetic polymorphisms with urothelial cell carcinoma susceptibility differ between smokers and non-smokers in Taiwan.

PubMed

Tung, Min-Che; Hsieh, Ming-Ju; Wang, Shian-Shiang; Yang, Shun-Fa; Chen, Shiou-Sheng; Wang, Shih-Wei; Lee, Liang-Ming; Lee, Wei-Jiunn; Chien, Ming-Hsien

2014-01-01

Vascular endothelial growth factor (VEGF)-C is associated with lymphangiogenesis, pelvic regional lymph node metastasis, and an antiapoptotic phenotype in urothelial cell carcinoma (UCC). Knowledge of potential roles of VEGF-C genetic polymorphisms in susceptibility to UCC is lacking. This study was designed to examine associations between VEGF-C gene variants and UCC susceptibility and evaluate whether they are modified by smoking. Five single-nucleotide polymorphisms (SNPs) of VEGF-C were analyzed by a TaqMan-based real-time polymerase chain reaction (PCR) in 233 patients with UCC and 520 cancer-free controls. A multivariate logistic regression was applied to model associations between genetic polymorphisms and UCC susceptibility, and to determine if the effect was modified by smoking. We found that after adjusting for other covariates, individuals within the entire population and the 476 non-smokers carrying at least one A allele at VEGF-C rs1485766 respectively had 1.742- and 1.834-fold risks of developing UCC than did wild-type (CC) carriers. Among the 277 smokers, we found that VEGF-C rs7664413 T (CT+TT) and rs2046463 G (AG+GG) allelic carriers were more prevalent in UCC patients than in non-cancer participants. Moreover, UCC patients with the smoking habit who had at least one T allele of VEGF-C rs7664413 were at higher risk of developing larger tumor sizes (p = 0.021), compared to those patients with CC homozygotes. Our results suggest that the involvement of VEGF-C genotypes in UCC risk differs among smokers compared to non-smokers among Taiwanese. The genetic polymorphism of VEGF-C rs7664413 might be a predictive factor for the tumor size of UCC patients who have a smoking habit.

Primary hyperoxaluria type 1: diagnostic relevance of mutations and polymorphisms in the alanine:glyoxylate aminotransferase gene (AGXT).

PubMed

Tarn, A C; von Schnakenburg, C; Rumsby, G

1997-09-01

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder of glyoxylate metabolism caused by deficiency of the hepatic peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). The disease shows considerable phenotypic, enzymatic and genetic heterogeneity. To date, 7 polymorphisms and 11 point mutations have been described in the gene encoding AGT. We report on the prevalence of these polymorphisms and mutations in 79 patients with PH1 with the aim of assessing their diagnostic relevance. A strong association of the C154T, intron 1 insertion and C386T polymorphisms is confirmed and this linkage extends to include the type 1 variant of a polymorphic tandem repeat in intron 4. Only 64 of 158 (40%) PH1 alleles have one of the defined mutations, with the G630A mutation accounting for 39 of these and T853C for 14. Overall only 20 (25%) of the patients studied had the genetic basis of their disease fully explained: 7 were homozygous for the G630A mutation, 5 were homozygous for the T853C mutation, 1 was homozygous for the C819T mutation, and 7 had two different mutations identified and were presumed to be compound heterozygotes. Only the two more frequent G630A and T853C mutations are of general diagnostic relevance for mutation screening. It seems likely that there are a significant number of other mutations, perhaps family-specific, still to be described. There was no apparent difference in the types of mutations in patients presenting in the first year of life (36%), suggesting that other factors, such as periods of dehydration or urinary tract infections, might contribute more to the clinical manifestation than genotype.

A preliminary study: novelty seeking, frontal executive function, and dopamine receptor (D2) TaqI A gene polymorphism in patients with methamphetamine dependence.

PubMed

Han, Doug Hyun; Yoon, Sujung J; Sung, Young Hoon; Lee, Young Sik; Kee, Baik Seok; Lyoo, In Kyoon; Renshaw, Perry F; Cho, Soo Churl

2008-01-01

Dopamine receptor polymorphisms have been associated with specific patterns of novelty seeking (NS) temperamental nature and frontal executive function. In addition, carriers of dopamine receptor type 2 (DRD2)-TaqI A1 have been hypothesized to be potentially vulnerable to addictive behaviors. In the present study, the association between dopamine D2 polymorphisms, NS, and frontal executive function was studied. Thirty-seven methamphetamine (MA)-dependent subjects and 40 healthy comparison subjects participated in the current study. The severity of addiction, NS temperament, and frontal executive functions were measured using the Addiction Severity Index, the NS subscale in the Temperament and Character Inventory, and the Wisconsin Card Sorting Test, respectively. All subjects were genotyped with regard to DRD2-TaqI polymorphisms. The prevalence of DRD2-TaqI A1 allele polymorphisms was greater in the MA-abuser group than in the comparison group. Patients with MA dependence also had higher NS characteristics and high scores in total trials, errors, and perseverative errors of the Wisconsin Card Sorting Test than comparison subjects. Within patients with MA dependence, the subgroup of DRD2-TaqI A1 carrier had greater NS scores relative to those without, whereas there was only a trend level of lower frontal executive function in the first subgroup. In the present study, the MA-dependent patients with DRD2-TaqI A1 allele had significantly greater NS scores and lower frontal executive function with a trend level than those without. These preliminary results suggest that MA-dependent patients may have the possibility of genetic and biogenic vulnerability to MA.

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

Uncoupling protein 2 gene polymorphisms are associated with obesity

PubMed Central

2012-01-01

Background Uncoupling protein 2 (UCP2) gene polymorphisms have been reported as genetic risk factors for obesity and type 2 diabetes mellitus (T2DM). We examined the association of commonly observed UCP2 G(−866)A (rs659366) and Ala55Val (C > T) (rs660339) single nucleotide polymorphisms (SNPs) with obesity, high fasting plasma glucose, and serum lipids in a Balinese population. Methods A total of 603 participants (278 urban and 325 rural subjects) were recruited from Bali Island, Indonesia. Fasting plasma glucose (FPG), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) were measured. Obesity was determined based on WHO classifications for adult Asians. Participants were genotyped for G(−866)A and Ala55Val polymorphisms of the UCP2 gene. Results Obesity prevalence was higher in urban subjects (51%) as compared to rural subjects (23%). The genotype, minor allele (MAF), and heterozygosity frequencies were similar between urban and rural subjects for both SNPs. All genotype frequencies were in Hardy-Weinberg equilibrium. A combined analysis of genotypes and environment revealed that the urban subjects carrying the A/A genotype of the G(−866)A SNP have higher BMI than the rural subjects with the same genotype. Since the two SNPs showed strong linkage disequilibrium (D’ = 0.946, r2 = 0.657), a haplotype analysis was performed. We found that the AT haplotype was associated with high BMI only when the urban environment was taken into account. Conclusions We have demonstrated the importance of environmental settings in studying the influence of the common UCP2 gene polymorphisms in the development of obesity in a Balinese population. PMID:22533685

Triosephosphate isomerase gene promoter variation: -5G/A and -8G/A polymorphisms in clinical malaria groups in two African populations.

PubMed

Guerra, Mónica; Machado, Patrícia; Manco, Licínio; Fernandes, Natércia; Miranda, Juliana; Arez, Ana Paula

2015-06-01

TPI1 promoter polymorphisms occur in high prevalence in individuals from African origin. Malaria-patients from Angola and Mozambique were screened for the TPI1 gene promoter variants rs1800200A>G, (-5G>A), rs1800201G>A, (-8G>A), rs1800202T>G, (-24T>G), and for the intron 5 polymorphism rs2071069G>A, (2262G>A). -5G>A and -8G>A variants occur in 47% and 53% in Angola and Mozambique, respectively while -24T>G was monomorphic for the wild-type T allele. Six haplotypes were identified and -8A occurred in 45% of the individuals, especially associated with the GAG haplotype and more frequent in non-severe malaria groups, although not significantly. The arising and dispersion of -5G>A and -8G>A polymorphisms is controversial. Their age was estimated by analyses of two microsatellite loci, CD4 and ATN1, adjacent to TPI1 gene. The -5G>A is older than -8G>A, with an average estimate of approximately 35,000 years. The -8A variant arose in two different backgrounds, suggesting independent mutational events. The first, on the -5G background, may have occurred in East Africa around 20,800 years ago; the second, on the -5A background, may have occurred in West Africa some 7500 years ago. These estimates are within the period of spread of agriculture and the malaria mosquito vector in Africa, which could has been a possible reason for the selection of -8A polymorphism in malaria endemic countries. Copyright © 2015 Elsevier B.V. All rights reserved.

Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics

PubMed Central

2014-01-01

Background Over the last decades, a vast structural knowledge has been gathered on the HIV-1 protease (PR). Noticeably, most of the studies focused the B-subtype, which has the highest prevalence in developed countries. Accordingly, currently available anti-HIV drugs target this subtype, with considerable benefits for the corresponding patients. However, in developing countries, there is a wide variety of HIV-1 subtypes carrying PR polymorphisms related to reduced drug susceptibility. The non-active site mutation, M36I, is the most frequent polymorphism, and is considered as a non-B subtype marker. Yet, the structural impact of this substitution on the PR structure and on the interaction with natural substrates remains poorly documented. Results Herein, we used molecular dynamics simulations to investigate the role of this polymorphism on the interaction of PR with six of its natural cleavage-sites substrates. Free energy analyses by MMPB/SA calculations showed an affinity decrease of M36I-PR for the majority of its substrates. The only exceptions were the RT-RH, with equivalent affinity, and the RH-IN, for which an increased affinity was found. Furthermore, molecular simulations suggest that, unlike other peptides, RH-IN induced larger structural fluctuations in the wild-type enzyme than in the M36I variant. Conclusions With multiple approaches and analyses we identified structural and dynamical determinants associated with the changes found in the binding affinity of the M36I variant. This mutation influences the flexibility of both PR and its complexed substrate. The observed impact of M36I, suggest that combination with other non-B subtype polymorphisms, could lead to major effects on the interaction with the 12 known cleavage sites, which should impact the virion maturation. PMID:25573486

Human genetic selection on the MTHFR 677C>T polymorphism

PubMed Central

Mayor-Olea, Álvaro; Callejón, Gonzalo; Palomares, Arturo R; Jiménez, Ana J; Gaitán, María Jesús; Rodríguez, Alfonso; Ruiz, Maximiliano; Reyes-Engel, Armando

2008-01-01

Background The prevalence of genotypes of the 677C>T polymorphism for the MTHFR gene varies among humans. In previous studies, we found changes in the genotypic frequencies of this polymorphism in populations of different ages, suggesting that this could be caused by an increase in the intake of folate and multivitamins by women during the periconceptional period. The aim was to analyze changes in the allelic frequencies of this polymorphism in a Spanish population, including samples from spontaneous abortions (SA). Methods A total of 1305 subjects born in the 20th century were genotyped for the 677C>T polymorphism using allele specific real-time PCR with Taqman® probes. A section of our population (n = 276) born in 1980–1989 was compared with fetal samples (n = 344) from SA of unknown etiology from the same period. Results An increase in the frequency of the T allele (0.38 vs 0.47; p < 0.001) and of the TT genotype (0.14 vs 0.24; p < 0.001) in subjects born in the last quarter of the century was observed. In the 1980–1989 period, the results show that the frequency of the wild type genotype (CC) is about tenfold lower in the SA samples than in the controls (0.03 vs 0.33; p < 0.001) and that the frequency of the TT genotype increases in the controls (0.19 to 0.27) and in the SA samples (0.20 to 0.33 (p < 0.01)); r = 0.98. Conclusion Selection in favor of the T allele has been detected. This selection could be due to the increased fetal viability in early stages of embryonic development, as is deduced by the increase of mutants in both living and SA populations. PMID:19040733

Mutations and new polymorphic changes in the TCOF1 gene of patients with oculo-auriculo-vertebral spectrum and Treacher-Collins syndrome.

PubMed

Su, Pen-Hua; Yu, Ju-Shan; Chen, Jia-Yuh; Chen, Suh-Jen; Li, Shuan-Yow; Chen, Hsiao-Neng

2007-10-01

Oculo-auriculo-vertebral spectrum, the exact genetic predisposition of which has not yet been resolved, is characterized by varying degrees of the prevalently unilateral underdevelopment of craniofacial structures and spinal anomalies. Here, we analyzed four cases exhibiting multiple features of oculo-auriculo-vertebral spectrum and one case with Treacher-Collins syndrome. The cranium was analyzed using three-dimensional computed tomography, which reliably identifies craniofacial malformations. We detected one typical oculo-auriculo-vertebral spectrum patient who had a missense mutation in exon 9 of the TCOF1 gene complex and two silent mutations in exons 10 and 23, three partial oculo-auriculo-vertebral spectrum patients who had no detectable mutations in the TCOF1 gene complex, and one Treacher-Collins syndrome patient who had a nonsense mutation in exon 14. All five patients had eight previously reported polymorphic changes in the TCOF1 exons 10, 11, 12, 16, 21, 22, and 23, and four unreported polymorphisms in exons 9, 17, and 22 that were also detected in 51 Taiwanese control patients. These observations strongly suggest that the TCOF1 genetic changes observed in these five patients might be related to oculo-auriculo-vertebral spectrum symptoms.

Long interspersed repeated DNA (LINE) causes polymorphism at the rat insulin 1 locus.

PubMed Central

Lakshmikumaran, M S; D'Ambrosio, E; Laimins, L A; Lin, D T; Furano, A V

1985-01-01

The insulin 1, but not the insulin 2, locus is polymorphic (i.e., exhibits allelic variation) in rats. Restriction enzyme analysis and hybridization studies showed that the polymorphic region is 2.2 kilobases upstream of the insulin 1 coding region and is due to the presence or absence of an approximately 2.7-kilobase repeated DNA element. DNA sequence determination showed that this DNA element is a member of a long interspersed repeated DNA family (LINE) that is highly repeated (greater than 50,000 copies) and highly transcribed in the rat. Although the presence or absence of LINE sequences at the insulin 1 locus occurs in both the homozygous and heterozygous states, LINE-containing insulin 1 alleles are more prevalent in the rat population than are alleles without LINEs. Restriction enzyme analysis of the LINE-containing alleles indicated that at least two versions of the LINE sequence may be present at the insulin 1 locus in different rats. Either repeated transposition of LINE sequences or gene conversion between the resident insulin 1 LINE and other sequences in the genome are possible explanations for this. Images PMID:3016521

Missense mutation of the cholecystokinin B receptor gene: Lack of association with panic disorder

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

Kato, Tadafumi; Wang, Zhe Wu; Crowe, R.R.

1996-07-26

Cholecystokinin tetrapeptide (CCK{sub 4}) is known to induce panic attacks in patients with panic disorder at a lower dose than in normal controls. Therefore, the cholecystokinin B (CCK{sub B}) receptor gene is a candidate gene for panic disorder. We searched for mutations in the CCK{sub B} gene in 22 probands of panic disorder pedigrees, using single-strand conformation polymorphism (SSCP) analysis. Two polymorphisms were detected. A polymorphism in an intron (2491 C{yields}A) between exons 4 and 5 was observed in 10 of 22 probands. A missense mutation in the extracellular loop of exon 2 (1550 G{yields}A, Val{sup 125}{yields}Ile) was found inmore » only one proband. This mutation was also examined in additional 34 unrelated patients with panic disorder and 112 controls. The prevalence rate of this mutation was 8.8% in patients with panic disorder (3/34) and 4.4% in controls (5/112). The mutation did not segregate with panic disorder in two families where this could be tested. These results suggest no pathophysiological significance of this mutation in panic disorder. 21 refs., 4 figs., 1 tab.« less

A case control association study of ACE gene polymorphism (I/D) with hypertension in Punjabi population from Faisalabad, Pakistan.

PubMed

Hussain, Misbah; Awan, Fazli Rabbi; Gujjar, Amna; Hafeez, Shakir; Islam, Mehboob

2018-01-01

Angiotensin converting enzyme (ACE) is a key component of renin angiotensin aldosterone system. It converts angiotensin I to angiotensin II. Insertion/deletion (I/D) polymorphism of ACE gene is found associated with several complications. However, its association with hypertension and related metabolic diseases is still controversial. So, the aim of the present study was to check this association for Punjabi population from Faisalabad, Pakistan. For this purpose, blood samples (patients = 100, controls = 48) were collected and several biochemical parameters were measured. Genotyping for ACE (I/D) polymorphism was performed by polymerase chain reaction (PCR) assay. ID genotype is found prevalent in the studied population as 41% in control subjects and 61% in patients. Furthermore, chi-square analysis showed significant (p = 0.005) difference for genotypic frequencies between both groups. One-way ANOVA for association of II, ID, and DD genotypes with anthropometric, clinical, and biochemical parameters showed that in patient group, DD genotype is significantly (p = 0.041) associated with systolic blood pressure (SBP). Moreover, ID genotype is found associated with the presence of cardiovascular diseases. This study concludes that DD genotype is strongly associated with higher SBP in hypertensive patients.

Complement Component C3 Variant (R102G) and the Risk of Neovascular Age-Related Macular Degeneration in a Tunisian Population.

PubMed

Habibi, Imen; Sfar, Imen; Kort, Fedra; Bouraoui, Rim; Chebil, Ahmed; Limaiem, Rim; Ayed, Saloua; Ben Abdallah, Taïeb; El Matri, Leila; Gorgi, Yousr

2017-04-01

Purpose To explore the association between the polymorphism (S/F) p.R102G in the complement component 3 ( C3 ) gene and age-related macular degeneration (AMD) in a Tunisian population. Methods The molecular study was performed by polymerase chain reaction using sequence-specific primers (PCR-SSP) in 207 control subjects free of any eye disease (fundus normal) and 145 patients with exudative AMD. The CH50 activity and quantification of C3 and C4 have been made by technical home method and nephelometry, respectively. Results The prevalence of C3 GG genotype polymorphism was significantly higher in AMD patients compared to controls (OR: 2.41, IC 95% [1.90-3.05], p = 0.0007). However, no correlation was found between this allelic variant and the type of neovascularization. Similarly, there is no association between this polymorphism and the presence of functional and/or quantitative hypocomplementemia. Conclusions The C3 GG genotype of the gene could be a susceptibility factor for AMD in the Tunisian population. However, it does not seem to influence the clinical profile of the disease. Georg Thieme Verlag KG Stuttgart · New York.

Association Study of the β2-Adrenergic Receptor Gene Polymorphisms and Hypertension in the Northern Han Chinese

PubMed Central

Li, Yao; Liu, Ya; Wang, Zuoguang; Liu, Kuo; Wu, Hai; Niu, Qiuli; Gu, Wei; Guo, Yanhong; Li, Zhizhong; Wen, Shaojun

2011-01-01

Background The β2-adrenergic receptor (ADRB2) gene has been widely researched as a candidate gene for essential hypertension (EH), but no consensus has been reached in different ethnicities. The aim of the present study was to evaluate the possible association between the ADRB2 gene polymorphisms and the EH risk in the Northern Han Chinese population. Methodology/Principal Findings This study included 747 hypertensive subjects and 390 healthy volunteers as control subjects in the Northern Han Chinese. Genotyping was performed to identify the C-47T, A46G and C79G polymorphisms of the ADRB2 gene. G allelic frequency of A46G polymorphism was significantly higher in hypertensive subjects (P = 0.011, OR = 1.287, 95%CI [1.059–1.565]) than that in controls. Significant association could also be found in dominant genetic model (GG+AG vs. AA, P = 0.006, OR = 1.497, 95%CI [1.121–1.998]), in homozygote comparison (GG vs. AA, P = 0.025, OR = 1.568, 95%CI [1.059–2.322]), and in additive genetic model (GG vs. AG vs. AA, P = 0.012, OR = 1.282, 95%CI [1.056–1.555]). Subgroup analyses performed by gender suggested that this association could be found in male, but not in female. Stratification analyses by obesity showed that A46G polymorphism was related to the prevalence of hypertension in the obese population (GG vs. AG vs. AA, P<0.001, OR = 1.645, 95%CI [1.258–2.151]). Significant interaction was found between A46G genotypes and body mass index on EH risk. No significant association could be found between C-47T or C79G polymorphism and EH risk. Linkage disequilibrium was detected between the C-47T, A46G and C79G polymorphisms. Haplotype analyses observed that the T-47-A46-C79 haplotype was a protective haplotype for EH, while the T-47-G46-C79 haplotype increased the risk. Conclusions/Significances We revealed that the ADRB2 A46G polymorphism might increase the risk for EH in the Northern Han Chinese population. PMID:21483652

Association between 5HT2A polymorphism and selective serotonin re-uptake inhibitor (SSRI)-induced sexual desire disorder (SDD) among Malaysian women.

PubMed

Masiran, Ruziana; Sidi, Hatta; Mohamed, Zahurin; Mohamed Saini, Suriati; Nik Jaafar, Nik Ruzyanei

2013-04-01

SSRIs are known for their sexual side-effects with a variable rate of sexual dysfunction (SD). 5HT2A (rs6311) single nucleotide polymorphism (SNP) was found to have significant association with SD. The purpose of this study was to determine the prevalence of female SDD, its clinical correlates and association with 5HT2A (rs6311) SNP in patients with major depressive disorder (MDD) treated with SSRIs. This was a cross-sectional study. We evaluated 95 female outpatients with MDD treated with SSRIs who were in remission. Outcome measures were stratified by the presence or absence of SDD. A buccal swab was obtained from each patient and sent for genotyping in the Pharmacogenomics and Medical Biotechnology Laboratory of Universiti Malaya. The overall prevalence of female SD was 32.6%. The prevalence of female SDD was 62.1%. Those with arousal problem, lubrication problem, sexual satisfaction problem, orgasm problem and problematic marriage were more likely to have sexual desire disorder. The majority of participants who had sexual desire disorder had genotype TT (42.4%) but there was no significant association observed. After controlling for age, number of children, education level, SSRI type, lubrication problem, orgasm problem, satisfaction problem and marital problem, only arousal problem significantly enhanced the presence of sexual desire disorder by 8.5 times (odds ratio = 8.46, 95% confidence interval = 1.24-57.58; P = 0.018). This study showed that there was no significant association between SDD and the 5HT2A (rs6311) SNP. Arousal problem significantly enhanced the presence of sexual desire disorder. Copyright © 2013 Wiley Publishing Asia Pty Ltd.

Silent dissemination of HTLV-1 in an endemic area of Argentina. Epidemiological and molecular evidence of intrafamilial transmission

PubMed Central

Gastaldello, Rene; Balangero, Marcos; Remondegui, Carlos; Blanco, Sebastián; Otsuki, Koko; Paulo Vicente, Ana Carolina; Elías, David; Mangeaud, Arnaldo; Nates, Silvia; Gallego, Sandra

2017-01-01

Background Molecular and epidemiological studies of transmission routes and risk factors for infection by HTLV-1 are extremely important in order to implement control measures, especially because of the high prevalence of HTLV-1 in several regions of the world. San Salvador de Jujuy, Northwest Argentina, is a highly endemic area for HTLV-1 and foci of tropical spastic paraparesis/HTLV-1-associated myelopathy. Objective To gain further insight into the role of intrafamilial transmission of HTLV-1 in a highly endemic region in Argentina. Method Cross-sectional study in Northwest Argentina. Epidemiological data and blood samples were collected from 28 HTLV-1 infected subjects (index cases) and 92 close relatives/cohabitants. HTLV-1 infection was diagnosed by detection of antibodies and proviral DNA. The LTR region was sequenced and analyzed for genetic distances (VESPA software), in addition to determination and identification of polymorphisms to define HTLV-1 family signatures. Results Fifty seven of the 120 subjects enrolled had antibodies against HTLV-1 and were typified as HTLV-1 by PCR. The prevalence rate of HTLV-1 infection in family members of infected index cases was 31.52% (29/92). The infection was significantly associated with gender, age and prolonged lactation. Identity of LTR sequences and presence of polymorphisms revealed high prevalence of mother-to-child and interspousal transmission of HTLV-1 among these families. Conclusion There is an ongoing and silent transmission of HTLV-1 through vertical and sexual routes within family clusters in Northwest Argentina. This evidence highlights that HTLV-1 infection should be considered as a matter of public health in Argentina, in order to introduce preventive measures as prenatal screening and breastfeeding control. PMID:28384180

Polymorphisms in the K13 Gene in Plasmodium falciparum from Different Malaria Transmission Areas of Kenya.

PubMed

de Laurent, Zaydah R; Chebon, Lorna J; Ingasia, Luicer A; Akala, Hoseah M; Andagalu, Ben; Ochola-Oyier, Lynette Isabella; Kamau, Edwin

2018-05-01

The development of artemisinin (ART)-resistant parasites in Southeast Asia (SEA) threatens malaria control globally. Mutations in the Kelch 13 (K13)-propeller domain have been useful in identifying ART resistance in SEA. ART combination therapy (ACT) remains highly efficacious in the treatment of uncomplicated malaria in Sub-Saharan Africa (SSA). However, it is crucial that the efficacy of ACT is closely monitored. Toward this effort, this study profiled the prevalence of K13 nonsynonymous mutations in different malaria ecological zones of Kenya and in different time periods, before (pre) and after (post) the introduction of ACT as the first-line treatment of malaria. Nineteen nonsynonymous mutations were present in the pre-ACT samples ( N = 64) compared with 22 in the post-ACT samples ( N = 251). Eight of these mutations were present in both pre- and post-ACT parasites. Interestingly, seven of the shared single-nucleotide polymorphisms were at higher frequencies in the pre-ACT than the post-ACT parasites. The A578S mutation reported in SSA and the V568G mutation reported in SEA were found in both pre- and post-ACT parasites, with their frequencies declining post-ACT. D584Y and R539K mutations were found only in post-ACT parasites; changes in these codons have also been reported in SEA with different amino acids. The N585K mutation described for the first time in this study was present only in post-ACT parasites, and it was the most prevalent mutation at a frequency of 5.2%. This study showed the type, prevalence, and frequency of K13 mutations that varied based on the malaria ecological zones and also between the pre- and post-ACT time periods.

A polymorphism in the glucocorticoid receptor gene is associated with refractory hypotension in premature infants.

PubMed

Ogasawara, Kei; Sato, Maki; Hashimoto, Koichi; Imamura, Takashi; Go, Hayato; Hosoya, Mitsuaki

2018-06-01

Glucocorticoids play an important role in endocrine control. The association of glucocorticoid receptor (GR) gene polymorphisms with altered sensitivity to glucocorticoid therapy has been reported in adults. However, there are few such reports in infants. The present study analyzed the prevalence of four GR polymorphisms in preterm infants born before 30 weeks of gestation and determined the associations between these polymorphisms and clinical outcomes in the infants. Totally, 41 preterm infants born at two hospitals in Fukushima were retrospectively screened for the presence of four GR gene polymorphisms, using a TaqMan single-nucleotide polymorphism genotyping assay. The effect of GR gene polymorphisms on clinical outcomes during hospitalization was evaluated. The following primary clinical outcomes were assessed: refractory hypotension in the acute phase and/or severe bronchopulmonary dysplasia, maximum dopamine and dobutamine doses administered, and total hydrocortisone dose administered in the first 48 h of life. Multivariate analysis with logistic regression was used to assess the association between clinical factors and refractory hypotension. Of the four GR polymorphisms, only the BclI polymorphism was detected. The genotype distribution was as follows: C/C, 33; C/G, 8; and G/G, 0 infants. Significant differences were observed between the C/C and C/G genotypes with respect to the following variables: refractory hypotension (6% vs. 50%), dopamine dose [3.0 (2.0-4.0) vs. 4.8 (4.0-7.5) μg/kg/min], dobutamine dose [2.4 (0.0-3.6) vs. 4.0 (0-10.0) μg/kg/min], and total hydrocortisone dose administered in the first 48 h of life [2.0 (0-10.0) vs. 6.0 (0-12.0) mg/kg]. Multivariate analysis showed that the BclI genotype (C/C) was significantly less associated with refractory hypotension in the acute phase (odds ratio, 0.008; 95% confidence interval, 0.000-0.371; p = 0.013). The incidence of refractory hypotension in infants with the C/C genotype was initially expected to be higher than that in infants with the C/G genotype. However, the results of this study were rather different from what we originally expected. The suppressive effect of antenatal steroid use on the HPA axis of the preterm infants with the BclI variant may be associated with refractory hypotension in the acute phase. Copyright © 2017. Published by Elsevier B.V.

[Patients with inherited trombophilia and recurrent pregnancy loss: incidence].

PubMed

Flores-Alatriste, José Daniel; Jacobo-Nájera, Sara; Segura-Rodríguez, Rubén; Stern-Colin y Nunes, Jorge Jaroslav

2014-06-01

Inherited thrombophilia is a genetic tendency to suffer thrombotic events clinically evident at an early age, with frequent re- currences without apparent cause. In recent years thrombophilia has earned a place as a primary risk factor for abnormal pregnancy. To determine the incidence of hereditary thrombophilia in patients with recurrent pregnancy loss. A retrospective, linear and descriptive study was conducted at Clinic of Reproduction IMMUNOREP with patients treated from January 2007 to December 2012. The study included patients with a diagnosis of recurrent pregnancy loss and inherited thrombophilia with laboratory studies of thrombophilia including different genes: G1619A (factor V Leiden), R2 H1299R (factor V polymorphism), C677T (methylenetetrahydrofolate reductase enzyme polymorphism), A1298C (methylenetetrahydrofolate reductase enzyme mutation), G20210A (mutation of the prothrombin gene), V34L (factor XIII polymorphism), 455G > A (fibrinogen gene mutation), 4G/5G (plasminogen activator inhibitor) and a/b L33P (ribosomal polymorphism of methylenetetrahydrofolate reductase enzyme). 211 files were reviewed and only 10.4% of patients were negative for hereditary thrombophilia, a percentage that is consistent with the results of different series of studies in patients with unexplained recurrent pregnancy loss. The most prevalent genetic condition was 4G/5G (plasminogen activator inhibitor, 85.5%) in homozygous and heterozygous with 63.4% (120) and 22.4% (42), respectively. It was demonstrated the direct relationship between thrombophilia and recurrent pregnancy loss depending on whether the patient is heterozygous or homozygous for the disease.

Absence of putative artemisinin resistance mutations among Plasmodium falciparum in Sub-Saharan Africa: a molecular epidemiologic study.

PubMed

Taylor, Steve M; Parobek, Christian M; DeConti, Derrick K; Kayentao, Kassoum; Coulibaly, Sheick Oumar; Greenwood, Brian M; Tagbor, Harry; Williams, John; Bojang, Kalifa; Njie, Fanta; Desai, Meghna; Kariuki, Simon; Gutman, Julie; Mathanga, Don P; Mårtensson, Andreas; Ngasala, Billy; Conrad, Melissa D; Rosenthal, Philip J; Tshefu, Antoinette K; Moormann, Ann M; Vulule, John M; Doumbo, Ogobara K; Ter Kuile, Feiko O; Meshnick, Steven R; Bailey, Jeffrey A; Juliano, Jonathan J

2015-03-01

Plasmodium falciparum parasites that are resistant to artemisinins have been detected in Southeast Asia. Resistance is associated with several polymorphisms in the parasite's K13-propeller gene. The molecular epidemiology of these artemisinin resistance genotypes in African parasite populations is unknown. We developed an assay to quantify rare polymorphisms in parasite populations that uses a pooled deep-sequencing approach to score allele frequencies, validated it by evaluating mixtures of laboratory parasite strains, and then used it to screen P. falciparum parasites from >1100 African infections collected since 2002 from 14 sites across sub-Saharan Africa. We found no mutations in African parasite populations that are associated with artemisinin resistance in Southeast Asian parasites. However, we observed 15 coding mutations, including 12 novel mutations, and limited allele sharing between parasite populations, consistent with a large reservoir of naturally occurring K13-propeller variation. Although polymorphisms associated with artemisinin resistance in P. falciparum in Southeast Asia are not prevalent in sub-Saharan Africa, numerous K13-propeller coding polymorphisms circulate in Africa. Although their distributions do not support a widespread selective sweep for an artemisinin-resistant phenotype, the impact of these mutations on artemisinin susceptibility is unknown and will require further characterization. Rapid, scalable molecular surveillance offers a useful adjunct in tracking and containing artemisinin resistance. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The distribution of apolipoprotein E gene polymorphism in Chinese civil aircrews, and a possible risk factor to their overweight and dyslipidemia is cumulative flight time.

PubMed

Huang, He; Liu, Jing; Feng, Yingjin; Chen, Weiru

2013-02-01

The prevalence of dyslipidemia and overweight is significantly higher in aircrews than that in general population. The purpose of the study was to examine the distribution of APOE gene polymorphism and the influence of which as well as occupational environment on dyslipidemia and overweight in Chinese civil aircrews. APOE gene polymorphism was investigated using PCR-RFLP, plasma lipid parameters were measured by standard enzymatic kits and personal information of the aircrews was collected through questionnaires. The allele frequencies among aircrews were ε2: 17.0%, ε3: 80.9%, and ε4: 2.1%, APOE gene polymorphism was associated with significant differences in TC and LDL-C. E2 individuals had the lowest TC and LDL-C concentrations, and E4 participants had the highest levels (p<0.001). In addition, the TC and LDL-C concentrations, as well as BMI rose with the increasing cumulative flying hours (p<0.05). The further logistic regression analysis showed the significant associations of BMI and dyslipidemia (p<0.0001, OR=2.093), cumulative flight time and overweight (p<0.0001, OR=1.560). The distribution of APOE alleles among aircrews was provided for the first time, which is not fully identical with that among general population. These data also suggested the cumulative flight time influenced dyslipidemia and overweight as an environmental contributor. Copyright © 2012 Elsevier B.V. All rights reserved.

Long-term effects of Garcinia cambogia/Glucomannan on weight loss in people with obesity, PLIN4, FTO and Trp64Arg polymorphisms.

PubMed

Maia-Landim, Andrea; Ramírez, Juan M; Lancho, Carolina; Poblador, María S; Lancho, José L

2018-01-24

Overweight and obesity are considered major health problems that contribute to increase mortality and quality of life. Both conditions have a high prevalence across the world reaching epidemic numbers. Our aim was to evaluate the effects of the administration of Garcinia cambogia (GC) and Glucomannan (GNN) on long-term weight loss in people with overweight or obesity. Prospective, not-randomized controlled intervention trial was conducted. We treated 214 subjects with overweight or obesity with GC and GNN (500 mg twice a day, each) for 6 months evaluating weight, fat mass, visceral fat, basal metabolic rate, and lipid and glucose blood profiles comparing them with basal values. Some patients were carriers of polymorphisms PLIN4 -11482G > A-, fat mass and obesity-associated (FTO) -rs9939609 A/T- and β-adrenergic receptor 3 (ADRB3) -Trp64Arg. Treatment produced weight loss, reducing fat mass, visceral fat, lipid and blood glucose profiles while increasing basal metabolic rate. Results were independent of sex, age or suffering from hypertension, diabetes mellitus type 2 or dyslipidemia and were attenuated in carriers of PLIN4, FTO, Trp64Arg polymorphisms. Administration of GC and GNN reduce weight and improve lipid and glucose blood profiles in people with overweight or obesity, although the presence of polymorphisms PLIN4, FTO and ADRB3 might hinder in some degree these effects. ISRCTN78807585, 19 September 2017, retrospective study.

Neuropsychiatric Genetics of Happiness, Friendships, and Politics: Hypothesizing Homophily (“Birds of a Feather Flock Together”) as a Function of Reward Gene Polymorphisms

PubMed Central

Blum, Kenneth; Oscar-Berman, Marlene; Bowirrat, Abdalla; Giordano, John; Madigan, Margaret; Braverman, Eric R.; Barh, Debmayla; Hauser, Mary; Borsten, Joan; Simpatico, Thomas

2013-01-01

Mindful of the new evolutionary ideas related to an emerging scientific focus known as omics, we propose that spiritual, social, and political behaviors may be tied in part to inheritable reward gene polymorphisms, as has been demonstrated for the addictions. If so, analyses of gene polymorphisms may assist in predicting liberalism or conservatism in partisan attachments. For example, both drinking (alcohol) and obesity seem to cluster in large social networks and are influenced by friends having the same genotype, in particular the DRD2 A1 allele. Likewise, voting, voting turnout and attachment to a particular political ideology is differentially related to various reward genes (e.g., 5HTT, MOA, DRD2, and DRD4), possibly predicting liberalism or conservatism. Moreover, voters’ genetic information may predict presidential outcomes more than the actual issues at hand or the presidential candidates themselves. Thus, political discussions on TV, radio, or other media may be morphed by one’s reward gene polymorphisms and as such, may explain the prevalence of generations of die-hard republicans and equally entrenched democratic legacies. Indeed, even in politics, birds of a feather (homophily) flock together. We caution that our proposal should be viewed mindfully awaiting additional research before definitive statements or conclusions can be derived from the studies to date, and we encourage large scale studies to confirm these earlier reports. PMID:23336089

Effect of Soluble Inducible Costimulator Level and Its Polymorphisms on Age-Related Macular Degeneration

PubMed Central

Yu, Honghua; Zou, Xiulan; Peng, Lianghong; Wang, Yong; Zhang, Chu

2013-01-01

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population. Evidence has shown that the human immune system may play critical roles in this disease. Inducible costimulator (ICOS) promotes T-cell activation, differentiation, and T:B-cell interactions. The aim of the study was to understand the effect of ICOS on the development of AMD from genetic polymorphism perspective and serum level perspective. Two ICOS polymorphisms, rs10183087A/C and rs10932037C/T, were tested in 223 AMD cases and 262 healthy controls. The serum level of soluble ICOS (sICOS) was compared among subjects with different genotypes, as well as between AMD patients and controls. Data showed that prevalence of rs10183087CC genotype was significantly increased in AMD than in controls (p=0.001). Function analysis revealed that subjects carrying rs10183087CC genotype had higher serum levels of sICOS than those with AA or AC genotypes (p<0.05). When we compared serum levels of sICOS between cases and controls, results showed that AMD patients had significantly increased sICOS levels than healthy donors (p<0.05). Also, wet type cases were observed to have higher sICOS levels than cases with dry type (p<0.05). These data suggested ICOS polymorphism could affect the susceptibility to AMD by elevating protein expression, and serum levels of sICOS may be closed correlated with the development and progression of this disease. PMID:24083358

Polymorphisms in NAT2 (N-acetyltransferase 2) gene in patients with systemic lupus erythematosus.

PubMed

Santos, Elaine Cristina Lima Dos; Pinto, Amanda Chaves; Klumb, Evandro Mendes; Macedo, Jacyara Maria Brito

To investigate potential associations of four substitutions in NAT2 gene and of acetylator phenotype of NAT2 with systemic lupus erythematosus (SLE) and clinical phenotypes. Molecular analysis of 481C>T, 590G>A, 857G>A, and 191G>A substitutions in the NAT2 gene was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, from DNA extracted from peripheral blood samples obtained from patients with SLE (n=91) and controls (n=97). The 857GA genotype was more prevalent among nonwhite SLE patients (OR=4.01, 95% CI=1.18-13.59). The 481T allele showed a positive association with hematological disorders that involve autoimmune mechanisms, specifically autoimmune hemolytic anemia or autoimmune thrombocytopenia (OR=1.97; 95% CI=1.01-3.81). Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

Molecular mapping of powdery mildew resistance gene Eg-3 in cultivated oat (Avena sativa L. cv. Rollo).

PubMed

Mohler, Volker; Zeller, Friedrich J; Hsam, Sai L K

2012-05-01

Powdery mildew is a prevalent fungal disease affecting oat (Avena sativa L.) production in Europe. Common oat cultivar Rollo was previously shown to carry the powdery mildew resistance gene Eg-3 in common with cultivar Mostyn. The resistance gene was mapped with restriction fragment length polymorphism (RFLP) markers from Triticeae group-1 chromosomes using a population of F(3) lines from a cross between A. byzantina cv. Kanota and A. sativa cv. Rollo. This comparative mapping approach positioned Eg-3 between cDNA-RFLP marker loci cmwg706 and cmwg733. Since both marker loci were derived from the long arm of barley chromosome 1H, the subchromosomal location of Eg-3 was assumed to be on the long arm of oat chromosome 17. Amplified fragment length polymorphism (AFLP) marker technology featured as an efficient means for obtaining markers closely linked to Eg-3.

Genetic analysis of LRRK2 functional domains in Brazilian patients with Parkinson's disease.

PubMed

Abdalla-Carvalho, C B; Santos-Rebouças, C B; Guimarães, B C; Campos, M; Pereira, J S; de Rosso, A L Zuma; Nicaretta, D H; Marinho e Silva, M; dos Santos, Mendonça J; Pimentel, M M G

2010-12-01

Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have been associated with Parkinson's disease (PD), and the majority of the pathogenic variants are located in the ROC and MAPKKK domains. Exons 29-31 and 38-44 (ROC and MAPKKK domains) were sequenced in 204 patients with PD, mostly Brazilian. We identified four polymorphisms, a novel silent variant p.R1398R and four substitutions: p.T1410M, p.G2019S, p.Y2189C and the novel variant p.C2139S. The most prevalent mutation was the p.G2019S (2.4%). We consider that the p.T1410M and the p.Y2189C variants are probably polymorphisms and that the p.C2139S mutation is potentially pathogenic. © 2010 The Author(s). European Journal of Neurology © 2010 EFNS.

Genetic variants influencing effectiveness of weight loss strategies.

PubMed

Deram, Sophie; Villares, Sandra M F

2009-03-01

Body weight excess has an increasingly high prevalence in the world. Obesity is a complex disease of multifactorial origin with a polygenic condition affected by environmental factors. Weight loss is a primary strategy to treat obesity and its morbidities. Weight changes through life depend on the interaction of environmental, behavioral and genetic factors. Interindividual variation of weight loss in response to different types of interventions (behavioral, caloric restriction, exercise, drug or surgery) has been observed. In this article, currently available data on the role of candidate gene polymorphisms in weight loss are reviewed. Even though control of weight loss by genotype was described in twin and family studies, it is premature to recommend use of genotyping in the design of therapeutic diets or drug treatment. Future studies will have to be large in order to assess the effects of multiple polymorphisms, and will have to control factors other than diet.

Effect of co-administration of cassava (Manihot esculenta Crantz) rich diet and alcohol in rats.

PubMed

Boby, R G; Indira, M

2004-01-01

The effects of co-administration of a cassava rich diet and alcohol in rats were investigated. The animals were divided into four groups (1) Control, (2) Alcohol, (3) Cassava and (4) Alcohol + Cassava. Consumption of alcohol along with cassava reduced the alcohol induced toxicity which was evidenced by the lower activities of GOT, GPT, GGT, acid phosphatase and alkaline phosphatase in the liver and serum of co-administered group. The pyruvate content in the blood increased while the lactate content, lactate/pyruvate ratio and the activity of LDH decreased in the blood due to co-administration. The blood cyanide content, serum thiocyanate content and the activities of rhodanase and beta-glucuronidase increased on co-administration. The histopathological studies also revealed that co-administration reduced the alcohol induced toxicity.

HIV-1 pol Diversity among Female Bar and Hotel Workers in Northern Tanzania

PubMed Central

Kiwelu, Ireen E.; Novitsky, Vladimir; Kituma, Elimsaada; Margolin, Lauren; Baca, Jeannie; Manongi, Rachel; Sam, Noel; Shao, John; McLane, Mary F.; Kapiga, Saidi H.; Essex, M.

2014-01-01

A national ART program was launched in Tanzania in October 2004. Due to the existence of multiple HIV-1 subtypes and recombinant viruses co-circulating in Tanzania, it is important to monitor rates of drug resistance. The present study determined the prevalence of HIV-1 drug resistance mutations among ART-naive female bar and hotel workers, a high-risk population for HIV-1 infection in Moshi, Tanzania. A partial HIV-1 pol gene was analyzed by single-genome amplification and sequencing in 45 subjects (622 pol sequences total; median number of sequences per subject, 13; IQR 5–20) in samples collected in 2005. The prevalence of HIV-1 subtypes A1, C, and D, and inter-subtype recombinant viruses, was 36%, 29%, 9% and 27%, respectively. Thirteen different recombination patterns included D/A1/D, C/A1, A1/C/A1, A1/U/A1, C/U/A1, C/A1, U/D/U, D/A1/D, A1/C, A1/C, A2/C/A2, CRF10_CD/C/CRF10_CD and CRF35_AD/A1/CRF35_AD. CRF35_AD was identified in Tanzania for the first time. All recombinant viruses in this study were unique, suggesting ongoing recombination processes among circulating HIV-1 variants. The prevalence of multiple infections in this population was 16% (n = 7). Primary HIV-1 drug resistance mutations to RT inhibitors were identified in three (7%) subjects (K65R plus Y181C; N60D; and V106M). In some subjects, polymorphisms were observed at the RT positions 41, 69, 75, 98, 101, 179, 190, and 215. Secondary mutations associated with NNRTIs were observed at the RT positions 90 (7%) and 138 (6%). In the protease gene, three subjects (7%) had M46I/L mutations. All subjects in this study had HIV-1 subtype-specific natural polymorphisms at positions 36, 69, 89 and 93 that are associated with drug resistance in HIV-1 subtype B. These results suggested that HIV-1 drug resistance mutations and natural polymorphisms existed in this population before the initiation of the national ART program. With increasing use of ARV, these results highlight the importance of drug resistance monitoring in Tanzania. PMID:25003939

HIV-1 pol diversity among female bar and hotel workers in Northern Tanzania.

PubMed

Kiwelu, Ireen E; Novitsky, Vladimir; Kituma, Elimsaada; Margolin, Lauren; Baca, Jeannie; Manongi, Rachel; Sam, Noel; Shao, John; McLane, Mary F; Kapiga, Saidi H; Essex, M

2014-01-01

A national ART program was launched in Tanzania in October 2004. Due to the existence of multiple HIV-1 subtypes and recombinant viruses co-circulating in Tanzania, it is important to monitor rates of drug resistance. The present study determined the prevalence of HIV-1 drug resistance mutations among ART-naive female bar and hotel workers, a high-risk population for HIV-1 infection in Moshi, Tanzania. A partial HIV-1 pol gene was analyzed by single-genome amplification and sequencing in 45 subjects (622 pol sequences total; median number of sequences per subject, 13; IQR 5-20) in samples collected in 2005. The prevalence of HIV-1 subtypes A1, C, and D, and inter-subtype recombinant viruses, was 36%, 29%, 9% and 27%, respectively. Thirteen different recombination patterns included D/A1/D, C/A1, A1/C/A1, A1/U/A1, C/U/A1, C/A1, U/D/U, D/A1/D, A1/C, A1/C, A2/C/A2, CRF10_CD/C/CRF10_CD and CRF35_AD/A1/CRF35_AD. CRF35_AD was identified in Tanzania for the first time. All recombinant viruses in this study were unique, suggesting ongoing recombination processes among circulating HIV-1 variants. The prevalence of multiple infections in this population was 16% (n = 7). Primary HIV-1 drug resistance mutations to RT inhibitors were identified in three (7%) subjects (K65R plus Y181C; N60D; and V106M). In some subjects, polymorphisms were observed at the RT positions 41, 69, 75, 98, 101, 179, 190, and 215. Secondary mutations associated with NNRTIs were observed at the RT positions 90 (7%) and 138 (6%). In the protease gene, three subjects (7%) had M46I/L mutations. All subjects in this study had HIV-1 subtype-specific natural polymorphisms at positions 36, 69, 89 and 93 that are associated with drug resistance in HIV-1 subtype B. These results suggested that HIV-1 drug resistance mutations and natural polymorphisms existed in this population before the initiation of the national ART program. With increasing use of ARV, these results highlight the importance of drug resistance monitoring in Tanzania.

Multiple Origins of Mutations in the mdr1 Gene—A Putative Marker of Chloroquine Resistance in P. vivax

PubMed Central

Schousboe, Mette L.; Ranjitkar, Samir; Rajakaruna, Rupika S.; Amerasinghe, Priyanie H.; Morales, Francisco; Pearce, Richard; Ord, Rosalyn; Leslie, Toby; Rowland, Mark; Gadalla, Nahla B.; Konradsen, Flemming; Bygbjerg, Ib C.; Roper, Cally; Alifrangis, Michael

2015-01-01

Background Chloroquine combined with primaquine has been the recommended antimalarial treatment of Plasmodium vivax malaria infections for six decades but the efficacy of this treatment regimen is threatened by chloroquine resistance (CQR). Single nucleotide polymorphisms (SNPs) in the multidrug resistance gene, Pvmdr1 are putative determinants of CQR but the extent of their emergence at population level remains to be explored. Objective In this study we describe the prevalence of SNPs in the Pvmdr1 among samples collected in seven P. vivax endemic countries and we looked for molecular evidence of drug selection by characterising polymorphism at microsatellite (MS) loci flanking the Pvmdr1 gene. Methods We examined the prevalence of SNPs in the Pvmdr1 gene among 267 samples collected from Pakistan, Afghanistan, Sri Lanka, Nepal, Sudan, São Tomé and Ecuador. We measured and diversity in four microsatellite (MS) markers flanking the Pvmdr1 gene to look evidence of selection on mutant alleles. Results SNP polymorphism in the Pvmdr1 gene was largely confined to codons T958M, Y976F and F1076L. Only 2.4% of samples were wildtype at all three codons (TYF, n = 5), 13.3% (n = 28) of the samples were single mutant MYF, 63.0% of samples (n = 133) were double mutant MYL, and 21.3% (n = 45) were triple mutant MFL. Clear geographic differences in the prevalence of these Pvmdr mutation combinations were observed. Significant linkage disequilibrium (LD) between Pvmdr1 and MS alleles was found in populations sampled in Ecuador, Nepal and Sri Lanka, while significant LD between Pvmdr1 and the combined 4 MS locus haplotype was only seen in Ecuador and Sri Lanka. When combining the 5 loci, high level diversity, measured as expected heterozygosity (He), was seen in the complete sample set (He = 0.99), while He estimates for individual loci ranged from 0.00–0.93. Although Pvmdr1 haplotypes were not consistently associated with specific flanking MS alleles, there was significant differentiation between geographic sites which could indicate directional selection through local drug pressure. Conclusions Our observations suggest that Pvmdr1 mutations emerged independently on multiple occasions even within the same population. In Sri Lanka population analysis at multiple sites showed evidence of local selection and geographical dispersal of Pvmdr1 mutations between sites. PMID:26539821

Mitochondrial G8292A and C8794T mutations in patients with Niemann-Pick disease type C.

PubMed

Masserrat, Abbas; Sharifpanah, Fatemeh; Akbari, Leila; Tonekaboni, Seyed Hasan; Karimzadeh, Parvaneh; Asharafi, Mahmood Reza; Mazouei, Safoura; Sauer, Heinrich; Houshmand, Massoud

2018-07-01

Niemann-Pick disease type C (NP-C) is a neurovisceral lipid storage disorder. At the cellular level, the disorder is characterized by accumulation of unesterified cholesterol and glycolipids in the lysosomal/late endosomal system. NP-C is transmitted in an autosomal recessive manner and is caused by mutations in either the NPC1 (95% of families) or NPC2 gene. The estimated disease incidence is 1 in 120,000 live births, but this likely represents an underestimate, as the disease may be under-diagnosed due to its highly heterogeneous presentation. Variants of adenosine triphosphatase (ATPase) subunit 6 and ATPase subunit 8 ( ATPase6/8 ) in mitochondrial DNA (mtDNA) have been reported in different types of genetic diseases including NP-C. In the present study, the blood samples of 22 Iranian patients with NP-C and 150 healthy subjects as a control group were analyzed. The DNA of the blood samples was extracted by the salting out method and analyzed for ATPase6/8 mutations using polymerase chain reaction sequencing. Sequence variations in mitochondrial genome samples were determined via the Mitomap database. Analysis of sequencing data confirmed the existence of 11 different single nucleotide polymorphisms (SNPs) in patients with NP-C1. One of the most prevalent polymorphisms was the A8860G variant, which was observed in both affected and non-affected groups and determined to have no significant association with NP-C incidence. Amongst the 11 polymorphisms, only one was identified in the ATPase8 gene, while 9 including A8860G were observed in the ATPase6 gene. Furthermore, two SNPs, G8292A and C8792A, located in the non-coding region of mtDNA and the ATPase6 gene, respectively, exhibited significantly higher prevalence rates in NP-C1 patients compared with the control group (P<0.01). The present study suggests that there may be an association between mitochondrial ATPase6/8 mutations and the incidence of NP-C disease. In addition, the mitochondrial SNPs identified maybe pathogenic mutations involved in the development and prevalence of NP-C. Furthermore, these results suggest a higher occurrence of mutations in ATPase6 than in ATPase8 in NP-C patients.

Selection of Plasmodium falciparum pfcrt and pfmdr1 polymorphisms after treatment with artesunate-amodiaquine fixed dose combination or artemether-lumefantrine in Liberia.

PubMed

Otienoburu, Sabina Dahlström; Maïga-Ascofaré, Oumou; Schramm, Birgit; Jullien, Vincent; Jones, Joel J; Zolia, Yah M; Houzé, Pascal; Ashley, Elizabeth A; Kiechel, Jean-René; Guérin, Philippe J; Le Bras, Jacques; Houzé, Sandrine

2016-09-05

Plasmodium falciparum uncomplicated malaria can successfully be treated with an artemisinin-based combination therapy (ACT). However resistance is spreading to the different ACT compounds; the artemisinin derivative and the partner drug. Studies of P. falciparum polymorphisms associated with drug resistance can provide a useful tool to track resistance and guide treatment policy as well as an in-depth understanding of the development and spread of resistance. The role of P. falciparum molecular markers in selection of reinfections was assessed in an efficacy trial comparing artesunate-amodiaquine fixed-dose combination with artemether-lumefantrine to treat malaria in Nimba County, Liberia 2008-2009. P. falciparum polymorphisms in pfcrt 76, pfmdr1 86, 184 and 1246, and pfmrp1 876 and 1466 were analysed by PCR-RFLP and pyrosequencing. High baseline prevalence of pfmdr1 1246Y was found in Nimba county (38 %). Pfmdr1 1246Y and pfmdr1 86+184+1246 haplotypes NYY and YYY were selected in reinfections in the artesunate-amodiaquine arm and pfcrt K76, pfmdr1 N86 and pfmdr1 haplotype NFD were selected in artemether-lumefantrine reinfections. Parasites harbouring pfmdr1 1246Y could reinfect earlier after treatment with artesunate-amodiaquine and parasites carrying pfmdr1 N86 could reinfect at higher lumefantrine concentrations in patients treated with artemether-lumefantrine. Although treatment is highly efficacious, selection of molecular markers in reinfections could indicate a decreased sensitivity or tolerance of parasites to the current treatments and the baseline prevalence of molecular markers should be closely monitored. Since individual drug levels and the day of reinfection were demonstrated to be key determinants for selection of reinfections, this data needs to be collected and taken into account for accurate evaluation of molecular markers for anti-malarial treatments. The protocols for the clinical trial was registered with Current Controlled Trials, under the Identifier Number ISRCTN51688713 on 9 October 2008.

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.

Antibodies to Polymorphic Invasion-Inhibitory and Non-Inhibitory Epitopes of Plasmodium falciparum Apical Membrane Antigen 1 in Human Malaria

PubMed Central

Mugyenyi, Cleopatra K.; Elliott, Salenna R.; McCallum, Fiona J.; Anders, Robin F.; Marsh, Kevin; Beeson, James G.

2013-01-01

Background Antibodies to P. falciparum apical membrane protein 1 (AMA1) may contribute to protective immunity against clinical malaria by inhibiting blood stage growth of P. falciparum, and AMA1 is a leading malaria vaccine candidate. Currently, there is limited knowledge of the acquisition of strain-specific and cross-reactive antibodies to AMA1 in humans, or the acquisition of invasion-inhibitory antibodies to AMA1. Methodology/Findings We examined the acquisition of human antibodies to specific polymorphic invasion-inhibitory and non-inhibitory AMA1 epitopes, defined by the monoclonal antibodies 1F9 and 2C5, respectively. Naturally acquired antibodies were measured in cohorts of Kenyan children and adults. Antibodies to the invasion-inhibitory 1F9 epitope and non-inhibitory 2C5 epitope were measured indirectly by competition ELISA. Antibodies to the 1F9 and 2C5 epitopes were acquired by children and correlated with exposure, and higher antibody levels and prevalence were observed with increasing age and with active P. falciparum infection. Of note, the prevalence of antibodies to the inhibitory 1F9 epitope was lower than antibodies to AMA1 or the 2C5 epitope. Antibodies to AMA1 ectodomain, the 1F9 or 2C5 epitopes, or a combination of responses, showed some association with protection from P. falciparum malaria in a prospective longitudinal study. Furthermore, antibodies to the invasion-inhibitory 1F9 epitope were positively correlated with parasite growth-inhibitory activity of serum antibodies. Conclusions/Significance Individuals acquire antibodies to functional, polymorphic epitopes of AMA1 that may contribute to protective immunity, and these findings have implications for AMA1 vaccine development. Measuring antibodies to the 1F9 epitope by competition ELISA may be a valuable approach to assessing human antibodies with invasion-inhibitory activity in studies of acquired immunity and vaccine trials of AMA1. PMID:23861883

Prevalence of naturally occurring protease inhibitor resistance-associated variants in hemodialysis and renal transplant patients with hepatitis C virus infection.

PubMed

Tavares, Rita C F; Feldner, Ana C C A; Pinho, João R R; Uehara, Silvia N O; Emori, Christini T; Carvalho-Filho, Roberto J; Silva, Ivonete S S; Santana, Rúbia A F; de Castro, Vanessa F D; Castoli, Gregório T F; Cristovão, Charliana U; Ferraz, Maria L C G

2017-07-01

Background NS3 protease inhibitors (PIs) were the first direct antiviral agents used for the treatment of hepatitis C virus. The combination of second-wave PIs with other direct antiviral agents enabled the use of interferon-free regimens for chronic kidney disease patients on dialysis and renal transplant (RTx) recipients, populations in which the use of interferon and ribavirin is limited. However, the occurrence of PI resistance-associated variants (RAVs), both baseline and induced by therapy, has resulted in the failure of many treatment strategies. Methods The aim of this study was to estimate the prevalence of PI RAVs and of the Q80K polymorphism in chronic kidney disease patients on hemodialysis and RTx recipients. Direct sequencing of the NS3 protease was performed in 67 patients (32 hemodialysis and 35 RTx).Results RAVs to PIs were detected in 18% of the patients: V55A (9%), V36L (1.5%), T54S (1.5%), S122N (1.5%), I170L (1.5%), and M175L (1.5%). Only 1.5% of the patients carried the Q80K polymorphism. The frequency of these mutations was more than two times higher in patients infected with GT1a (25%) than GT1b (9.7%) (P=0.1). The mutations were detected in 20% of treatment-naive patients and in 15.6% of peginterferon/ribavirin-experienced patients (P=0.64). Furthermore, no mutation that would confer high resistance to PIs was detected.Conclusion The Q80K polymorphism was rare in the population studied. The occurrence of RAVs was common, with predominance in GT1a. However, the variants observed were those associated with a low level of resistance to PIs, facilitating the use of these drugs in this special group of patients.

Low prevalence of Borrelia bavariensis in Ixodes ricinus ticks in southeastern Austria.

PubMed

Glatz, Martin; Muellegger, Robert R; Hizo-Teufel, Cecilia; Fingerle, Volker

2014-10-01

Borrelia bavariensis was recently described as a distinct genospecies among the B. burgdorferi sensu lato complex. The prevalence of B. bavariensis in Austria, a highly endemic area for tick-transmitted pathogens, is scarcely characterized. To investigate the prevalence of B. bavariensis in Ixodes ricinus ticks we reevaluated the results of a study conducted in 518 ticks from southeastern Austria collected in 2002 and 2003. The presence of B. burgdorferi s.l.-specific DNA in ticks was analyzed by a PCR for the outer surface protein A (ospA) gene. Borrelia species were differentiated by restriction fragment length polymorphism (RFLP) analysis, and samples positive for B. bavariensis were further analyzed by multilocus sequence analysis. Two of 133 (1.5%) B. burgdorferi s.l.-positive I. ricinus ticks were infected with B. bavariensis. Both specimens were coinfected with the OspA serotype 5 of B. garinii. Borrelia bavariensis is present; however, seem to be rare in I. ricinus ticks in southeastern Austria. Copyright © 2014 Elsevier GmbH. All rights reserved.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency among tribal populations of India - Country scenario.

PubMed

Mukherjee, Malay B; Colah, Roshan B; Martin, Snehal; Ghosh, Kanjaksha

2015-05-01

It is believed that the tribal people, who constitute 8.6 per cent of the total population (2011 census of India), are the original inhabitants of India. Glucose-6-phosphate-dehydrogenase (G6PD) deficiency is an X-linked genetic defect, affecting around 400 million people worldwide and is characterized by considerable biochemical and molecular heterogeneity. Deficiency of this enzyme is highly polymorphic in those areas where malaria is/has been endemic. G6PD deficiency was reported from India more than 50 years ago. t0 he prevalence varies from 2.3 to 27.0 per cent with an overall prevalence of 7.7 per cent in different tribal groups. Since the tribal populations live in remote areas where malaria is/has been endemic, irrational use of antimalarial drugs could result in an increased number of cases with drug induced haemolysis. Therefore, before giving antimalarial therapy, routine screening for G6PD deficiency should be undertaken in those tribal communities where its prevalence is high.

Culture-gene coevolution of individualism-collectivism and the serotonin transporter gene.

PubMed

Chiao, Joan Y; Blizinsky, Katherine D

2010-02-22

Culture-gene coevolutionary theory posits that cultural values have evolved, are adaptive and influence the social and physical environments under which genetic selection operates. Here, we examined the association between cultural values of individualism-collectivism and allelic frequency of the serotonin transporter functional polymorphism (5-HTTLPR) as well as the role this culture-gene association may play in explaining global variability in prevalence of pathogens and affective disorders. We found evidence that collectivistic cultures were significantly more likely to comprise individuals carrying the short (S) allele of the 5-HTTLPR across 29 nations. Results further show that historical pathogen prevalence predicts cultural variability in individualism-collectivism owing to genetic selection of the S allele. Additionally, cultural values and frequency of S allele carriers negatively predict global prevalence of anxiety and mood disorder. Finally, mediation analyses further indicate that increased frequency of S allele carriers predicted decreased anxiety and mood disorder prevalence owing to increased collectivistic cultural values. Taken together, our findings suggest culture-gene coevolution between allelic frequency of 5-HTTLPR and cultural values of individualism-collectivism and support the notion that cultural values buffer genetically susceptible populations from increased prevalence of affective disorders. Implications of the current findings for understanding culture-gene coevolution of human brain and behaviour as well as how this coevolutionary process may contribute to global variation in pathogen prevalence and epidemiology of affective disorders, such as anxiety and depression, are discussed.

The birth prevalence of PKU in populations of European, South Asian and sub-Saharan African ancestry living in South East England.

PubMed

Hardelid, P; Cortina-Borja, M; Munro, A; Jones, H; Cleary, M; Champion, M P; Foo, Y; Scriver, C R; Dezateux, C

2008-01-01

Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism (OMIM 261600). Treatment with a low-phenylalanine diet following early ascertainment by newborn screening prevents impaired cognitive development, the major disease phenotype in PKU. The overall birth prevalence of PKU in European, Chinese and Korean populations is approximately 1/10,000. Since the human PAH locus contains PKU-causing alleles and polymorphic core haplotypes that describe and corroborate an out-of-Africa range expansion in modern human populations, it is of interest to know the prevalence of PKU in different ethnic groups with diverse geographical origin. We estimated PKU prevalence in South East England, where a sizeable proportion of the population are of Sub-Saharan African or South Asian ancestry. Over the period 1994 to 2004 167 children were diagnosed with PKU. Using birth registration and census data to derive denominators, PKU birth prevalence per 10,000 live births (95% Bayesian credible intervals) was estimated to be 1.14 (0.96-1.33) among white, 0.11 (0.02-0.37) among black, and 0.29 (0.10-0.63) among Asian ethnic groups. This suggests that PKU is up to an order of magnitude less prevalent in populations with Sub-Saharan African and South Asian ancestry that have migrated to the UK.

Prevalence of the rs1801282 single nucleotide polymorphism of the PPARG gene in patients with metabolic syndrome.

PubMed

Rocha, Renato Marano; Barra, Gustavo Barcelos; Rosa, Érica Carine Campos Caldas; Garcia, Érica Correa; Amato, Angélica Amorim; Azevedo, Monalisa Ferreira

2015-08-01

This study aimed to get the genotypic and allelic frequencies of rs1801282 in 179 volunteer donors and 154 patients with Metabolic syndrome (MetS) in Brasilia, Brazil and also examine the association with anthropometric, biochemical and hemodynamic variables in the latter group. MetS comprises a group of diseases resulting from insulin resistance, in-creased risk of type 2 diabetes and atherosclerotic cardiovascular disease. MetS is defined by the presence of increased visceral fat, atherogenic dyslipidemia (elevated triglycerides (TGL)), with decreased high density lipoprotein (HDL) and increased low density lipoprotein (LDL) levels, hypertension (BPH) and disturbances in glucose homeostasis representing a significant burden across the world due to the alarming increase in the incidence over the last decades besides their significant morbidity and mortality. Peroxisome proliferator activated receptor-gamma (PPARg) has been mentioned as a candidate gene for determining the risk of MetS. It is a member of the nuclear receptors superfamily and a ligand-activated transcription factor, which regulates the expression of genes involved in the network lipogenesis and adipogenesis, insulin sensitivity, energy balance, inflammation, angiogenesis and atherosclerosis. Among the PPARG genetic variants, single nucleotide polymorphism rs1801282 has been the most extensively studied one since it was first described by Yen and cols. in 1997. This polymorphism is characterized by the replacement of a proline (CCC) to an alanine (GCA) at codon 12 of exon B, due to the exchange of a cytosine with a guanine. The Ala allele frequency varies in different ethnic groups. DNA was extracted using Chelex-100 method and determinations of genotypes were performed by allele-specific chain reaction. The distribution of genotype frequency of the MetS group was not statistically different from the frequency in the donor population at large. In the first group, genotype frequency was CC to 0.869 and 0.103 for CG, while allelic frequencies were 0.948 for C and 0.052 for G allele. In the group of donors, the genotype and allele frequencies were 0.882 for CC, 0.117 to CG; and 0.941 to 0.059 for G and C, respectively. GG genotype was not found in any of the two groups. The genotype distribution and allele frequencies were in Hardy-Weinberg equilibrium. No marker could be detected from the analysis of anthropometric, biochemical and hemodynamic variables in the MetS group. Our data suggest that this polymorphism is not correlated with predisposition to MetS. The results obtained on a small sample of the population of Brasilia, corroborate the data reported in the literature on the prevalence of this polymorphism in PPAR in populations of different ethnic origins.

The Prevalence of Mixed Helicobacter pylori Infections in Symptomatic and Asymptomatic Subjects in Dhaka, Bangladesh.

PubMed

Kibria, Khandoker Mohammad K; Hossain, Md Enayet; Sultana, Jinath; Sarker, Shafiqul A; Bardhan, Pradip Kumar; Rahman, Motiur; Nahar, Shamsun

2015-10-01

Helicobacter pylori is a highly genetically diverse bacterial species, which can persist in the gastric environment for decades. Recent studies have shown that single infections predominate in developed countries, whereas mixed infections are more prevalent in developing countries. Mixed infections of this bacterium may be important for adaptation to the hostile gastric environment and may facilitate dyspeptic symptoms. To calculate the prevalence of mixed infections in symptomatic and asymptomatic subjects, 2010 H. pylori isolates collected from 83 symptomatic and 91 asymptomatic subjects from Dhaka, Bangladesh, were analyzed by (i) random amplified polymorphic DNA fingerprinting (RAPD) and (ii) multiplex PCR amplification for cagA and vacA virulence gene alleles. The overall prevalence of mixed H. pylori infection was 60.15% (77/128), indicating substantial co-colonization in this population. We additionally found that symptomatic subjects (53%) had a significantly higher rate of mixed infection than asymptomatic individuals (36.3%) (p = .016) and that the prevalence of the cagA and vacA and vacA m1/s1 and vacA m2/s1 alleles were higher in subjects with mixed infection. Our findings suggest that an increased diversity of the H. pylori strains in the gastric environment may contribute to the development of disease symptoms. © 2015 John Wiley & Sons Ltd.

A study of blood serotonin and serotonin transporter promoter variant (5-HTTLPR) polymorphism in Egyptian autistic children.

PubMed

Meguid, Nagwa A; Gebril, Ola H; Khalil, Rehab O

2015-01-01

Autism spectrum disorder (ASD) is a complex, heterogeneous neurodevelopmental disorder with onset during early childhood. Most studies have reported an elevation in platelet serotonin in persons with autism. The serotonin (5-hydroxytryptamine; 5-HT) transporter in the brain uptakes 5-HT from extracellular spaces. It is also present in platelets, where it takes up 5-HT from plasma. Polymorphisms in serotonin transporter gene (SLC6A4) were frequently studied in many neuropsychiatric disorders. We have measured the plasma 5-HT levels in 20 autistic male children and 20 control male children by the enzyme-linked immunosorbent assay (ELISA) method. In addition, the SLC6A4 promoter region (5-HTTLPR) insertion/deletion (I/D) polymorphism was studied, using whole genomic DNA. Plasma serotonin was significantly low in autistic children compared to control (P = 0.001), although correlation to severity of autism was not significant. The frequency of short (S) allele in autism cases was 10% and in the control group it was absent. Our study demonstrated an increased prevalence of 5-HTTLPR S allele in autism subjects. Significantly decreased plasma serotonin was detected in autism subjects, with no significant relationship between 5-HTTLPR genotype and plasma 5-HT being evident.

A study of blood serotonin and serotonin transporter promoter variant (5-HTTLPR) polymorphism in Egyptian autistic children

PubMed Central

Meguid, Nagwa A.; Gebril, Ola H.; Khalil, Rehab O.

2015-01-01

Background: Autism spectrum disorder (ASD) is a complex, heterogeneous neurodevelopmental disorder with onset during early childhood. Most studies have reported an elevation in platelet serotonin in persons with autism. The serotonin (5-hydroxytryptamine; 5-HT) transporter in the brain uptakes 5-HT from extracellular spaces. It is also present in platelets, where it takes up 5-HT from plasma. Polymorphisms in serotonin transporter gene (SLC6A4) were frequently studied in many neuropsychiatric disorders. Materials and Methods: We have measured the plasma 5-HT levels in 20 autistic male children and 20 control male children by the enzyme-linked immunosorbent assay (ELISA) method. In addition, the SLC6A4 promoter region (5-HTTLPR) insertion/deletion (I/D) polymorphism was studied, using whole genomic DNA. Results: Plasma serotonin was significantly low in autistic children compared to control (P = 0.001), although correlation to severity of autism was not significant. The frequency of short (S) allele in autism cases was 10% and in the control group it was absent. Conclusion: Our study demonstrated an increased prevalence of 5-HTTLPR S allele in autism subjects. Significantly decreased plasma serotonin was detected in autism subjects, with no significant relationship between 5-HTTLPR genotype and plasma 5-HT being evident. PMID:26015920

Association of Toll-Like Receptor 3 and Toll-Like Receptor 9 Single Nucleotide Polymorphisms with Hepatitis C Virus Infection and Hepatic Fibrosis in Egyptian Patients

PubMed Central

Zayed, Rania A.; Omran, Dalia; Mokhtar, Doha A.; Zakaria, Zinab; Ezzat, Sameera; Soliman, Mohamed A.; Mobarak, Lamiaa; El-Sweesy, Hossam; Emam, Ghada

2017-01-01

Toll-like receptors (TLRs) are recognized as fundamental contributors to the immune system function against infections. Hepatitis C virus (HCV) infection represents a global health problem especially in Egypt having the highest HCV prevalence worldwide where HCV infection is a continuing epidemic. The aim of the present study was to investigate the possible association between genetic variation in TLR-3 and TLR-9 and HCV infection and hepatic fibrosis in chronic HCV-positive Egyptian patients. The present study included 100 naïve chronic HCV-positive patients and 100 age- and sex-matched healthy controls. Genotyping of TLR-3 (_7 C/A [rs3775296]), TLR-3 (c.1377C/T [rs3775290]) and TLR-9 (1237T/C [rs5743836]) were done by polymerase chain reaction restriction fragment length polymorphism technique. Frequency of polymorphic genotypes in TLR-3 (_7 C/A), TLR-3 (c.1377C/T) and TLR-9 (1237T/C) were not significantly different between studied HCV-positive patients and controls with P values 0.121, 0.112, and 0.683, respectively. TLR-3 c.1377 T-allele was associated with advanced stage of hepatic fibrosis (P = 0.003). PMID:28093541

Plasminogen Activator Inhibitor-1 4G/5G Polymorphism is Associated with Reproductive Failure: Metabolic, Hormonal, and Immune Profiles.

PubMed

Salazar Garcia, Maria D; Sung, Nayoung; Mullenix, Thomas M; Dambaeva, Svetlana; Beaman, Kenneth; Gilman-Sachs, Alice; Kwak-Kim, Joanne

2016-07-01

Association between PAI-1 4G/5G polymorphism and reproductive failures has been postulated. We aimed to investigate its impact on metabolic, hormonal, and immune profiles of women with reproductive failures. A retrospective study was carried out in 208 women with a history of reproductive failure. Study patients were divided into three groups: women with repeated implantation failure (RIF, n = 40), recurrent pregnancy loss (RPL, n = 113), and both RIF and RPL (n = 55). Fertile controls were 92. PAI-1 4G/4G was prevalent in RPL, RIF, and RIF/RPL groups when compared with controls (P = 0.003) and associated with increased risks of RIF, RPL, and RIF with RPL (OR = 4.5, 2.2 and 2.7). Women with PAI-1 4G/4G have significantly higher BMI, glucose, and PAI-1 levels and lower NK cytotoxicity when compared with women without PAI-1 4G/4G. PAI-1 4G/5G polymorphism plays a major role in the pathogenesis of RPL and RIF by altering metabolic and immunological profiles. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Molecular Characteristics of the Mycobacterium tuberculosis LAM-RUS Family Prevalent in Central Russia▿ †

PubMed Central

Dubiley, Svetlana; Kirillov, Eugene; Ignatova, Anna; Stepanshina, Valentina; Shemyakin, Igor

2007-01-01

We analyzed IS6110-associated polymorphisms in the phospholipase C genes of 107 isolates of Mycobacterium tuberculosis selected to be representative of isolates circulating in central Russia. We found that the majority of Latin American-Mediterranean family strains contained an insertion in a unique position in the plcA gene, suggesting a common ancestor. This insertion can serve as a specific genetic marker for this group, which we designate the LAM-RUS family. PMID:17942651

Molecular surveillance for drug-resistant Plasmodium falciparum in clinical and subclinical populations from three border regions of Burma/Myanmar: cross-sectional data and a systematic review of resistance studies.

PubMed

Brown, Tyler; Smith, Linda S; Oo, Eh Kalu Shwe; Shawng, Kum; Lee, Thomas J; Sullivan, David; Beyrer, Chris; Richards, Adam K

2012-09-19

Confirmation of artemisinin-delayed parasite clearance in Plasmodium falciparum along the Thai-Myanmar border has inspired a global response to contain and monitor drug resistance to avert the disastrous consequences of a potential spread to Africa. However, resistance data from Myanmar are sparse, particularly from high-risk areas where limited health services and decades of displacement create conditions for resistance to spread. Subclinical infections may represent an important reservoir for resistance genes that confer a fitness disadvantage relative to wild-type alleles. This study estimates the prevalence of resistance genotypes in three previously unstudied remote populations in Myanmar and tests the a priori hypothesis that resistance gene prevalence would be higher among isolates collected from subclinical infections than isolates collected from febrile clinical patients. A systematic review of resistance studies is provided for context. Community health workers in Karen and Kachin States and an area spanning the Indo-Myanmar border collected dried blood spots from 988 febrile clinical patients and 4,591 villagers with subclinical infection participating in routine prevalence surveys. Samples positive for P. falciparum 18 s ribosomal RNA by real-time PCR were genotyped for P. falciparum multidrug resistance protein (pfmdr1) copy number and the pfcrt K76T polymorphism using multiplex real-time PCR. Pfmdr1 copy number increase and the pfcrt K76 polymorphism were determined for 173 and 269 isolates, respectively. Mean pfmdr1 copy number was 1.2 (range: 0.7 to 3.7). Pfmdr1 copy number increase was present in 17.5%, 9.6% and 11.1% of isolates from Karen and Kachin States and the Indo-Myanmar border, respectively. Pfmdr1 amplification was more prevalent in subclinical isolates (20.3%) than clinical isolates (6.4%, odds ratio 3.7, 95% confidence interval 1.1 - 12.5). Pfcrt K76T prevalence ranged from 90-100%. Community health workers can contribute to molecular surveillance of drug resistance in remote areas of Myanmar. Marginal and displaced populations under-represented among previous resistance investigations can and should be included in resistance surveillance efforts, particularly once genetic markers of artemisinin-delayed parasite clearance are identified. Subclinical infections may contribute to the epidemiology of drug resistance, but determination of gene amplification from desiccated filter samples requires further validation when DNA concentration is low.

[Possible pathogenetic role of 11 beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) gene polymorphisms in arterial hypertension].

PubMed

Morales, Mauricio A; Carvajal, Cristián A; Ortiz, Eugenia; Mosso, Lorena M; Artigas, Rocío A; Owen, Gareth I; Fardella, Carlos E

2008-06-01

Cortisol has been implicated in hypertension and lately reported to be regulated at the pre-receptor level by the 11betaHSD1 enzyme, which converts cortisone (E) to cortisol (F). Over-expression of this enzyme in adipose tissue could determine an increase in available cortisol that interacts with the mineralocorticoid receptor (MR) in renal, brain and heart tissue, leading to similar hypertensive effects as in 11betaHSD2 impaired patients. Several polymorphisms have been reported in HSDl IB 1 gene (CAI5, CAI9 and InsA83557), which could modify HSDl IB 1 gene expression or activity. To determine the distribution and prevalence of CAI5, CAI9 and InsA83557 in the HSDl IBl gene, and to correlate these results with biochemical parameters in cortisol/ ACTH (HPA) and renin-angiotensin-aldosterone (RAA) axis in patients with essential hypertension (EH). We studied 113 EH patients (76 non-obese and 37 obese, with a body mass índex >30 kg/m(2)) and 30 normotensive adults (NT). In each patient, we measured serum levels of E E, serum aldosterone (SA), plasma renin activity (PRA), adrenocorticotrophic hormone (ACTH), the urinary free cortisol/creatinine (UFF/Cr), F/ACTH and SA/PRA ratios. Each polymorphism was studied by PCR and 8% polyacrylamide gel electrophoresis. Statistical associations were evaluated by Pearson correlations and the genetic equilibrium by the Hardy-Weinberg (H-W) equation. We found all three polymorphisms in the EH and the NT group, both in genetic equilibrium. In obese essential hypertensives, the CAI5 polymorphism showed association with SA/PRA ratio (r =0.189, p =0.012) and F/ACTH (r =0.301, p 0.048); CA19 also showed correlation with F/ACTH in obese EH (r = 0.220, p 0.009). The InsA83557polymorphism correlated with UFF/Cr in both EH (r =0.206; p =0.03), and in obese EH (r =0.354; p =0.05). The CAI5 and CAI9 polymorphism correlated with changes in biochemical parameters in HPA and RAA axis of obese essential hypertensives. These changes may result in modifications in the expression of 11betaHSD1, leading to increased cortisol and aldosterone levels independent of ACTH and renin control, respectively.

Association Study between Coronary Artery Disease and rs1333049 and rs10757274 Polymorphisms at 9p21 Locus in South-West Iran

PubMed Central

Foroughmand, Ali Mohammad; Nikkhah, Emad; Galehdari, Hamid; Jadbabaee, Mohammad Hossin

2015-01-01

Objective Coronary artery disease (CAD) is a multi-factorial and heterogenic disease with atherosclerosis plaques formation in internal wall of coronary artery. Plaque formation results to limitation of the blood reaching to myocardium leading to appearance of some problems, such as ischemia, sudden thrombosis veins and myocardial infarction (MI). Several environmental and genetic factors are involved in prevalence and incident of CAD as follows: hypertension, high low density lipoprotein-cholesterol (LDL-C), age, diabetes mellitus, family history of early-onset heart disease and smoking. According to genome wide association studies (GWAS), five polymorphisms in the 9p21 locus seem to be associated with the CAD. We aimed to evaluate the remarkable association of two polymorphisms at 9p21 locus, rs1333049 and rs10757274, with CAD. Materials and Methods This experimental study was conducted in Golestan, Aria Hospitals and Genetics Lab of Shahid Chamran University in the city of Ahvaz, Iran, in 2010- 2011. The collected blood samples belonging to 170 CAD patients (case group) and 100 healthy individuals (control group) were analyzed by tetra-primer amplification refractory mutation system (ARMS)-polymerase chain reaction (PCR) technique. The results were analyzed using software package used for statistical analysis (SPSS; SPSS Inc., USA) version 16. A value of p<0.05 and an odd ratio (OR) with 95% confidence intervals (CI) were considered significant. Results The frequencies of CC, CG and GG genotypes for rs1333049 polymorphism in patients were 18.2, 65.3 and 16.5%, while in controls, the related values were 25, 67 and 8%, respectively. GG genotypes of rs1333049 polymorphism in CAD patients were more than control cases (OR: 0.354, 95%CI: 0.138-0.912, p=0.032). The frequencies of AA, AG and GG genotypes for rs10757274 in CAD patients were 8.2, 58.3 and 33.5%, while in controls, the related values were 35, 63 and 2%, respectively. GG Genotype in rs10757274 polymorphism in CAD patients was found more than control cases (OR: 0.014, 95% CI: 0.003 -0.065, p=0.0001). Conclusion The rs1333049 polymorphism at 9p21 locus shows a weak association with CAD, whereas rs10757274 polymorphism reveals a significant association with CAD. These variants may help the identification of patients with increased risk for coronary artery disease. PMID:25870838

Type 2 diabetes mellitus: association study of five candidate genes in an Indian population of Guadeloupe, genetic contribution of FABP2 polymorphism.

PubMed

Boullu-Sanchis, S; Leprêtre, F; Hedelin, G; Donnet, J P; Schaffer, P; Froguel, P; Pinget, M

1999-06-01

We studied by PCR-RFLP 6 polymorphisms in these 5 candidate genes: Ala54Thr in the fatty acid binding protein 2 gene (FABP2), A to G substitution in the uncoupling protein type 1 gene (UCP1), Asp905Tyr in the protein phosphatase type 1 gene (PP1G), Trp64Arg in the human beta 3 adrenergic receptor gene (beta 3AR) and 2 RFLP sites of the vitamin D receptor (VDR) gene (VDRTaq1 and VDRApa1). This study was conducted among 89 cases and 100 controls matched according to age, gender and absence of first degree family link (11 triplets with 2 controls for 1 case and 78 pairs with 1 control for 1 case). Cases and controls were taken among a sample of 429 individuals selected for the study of the prevalence of diabetes in this ethnic group from Guadeloupe. By conditional logistic regression analysis, there was a significant relation (p = 0.02) between the Ala54Thr FABP2 polymorphism and Type 2 DM. Multivariate analysis discriminate the FABP2 polymorphism (p = 0.10), a triglyceridemia over 2 g/l (p < 10(-3)) and high blood pressure (p = 10(-2)) as variables associated with Type 2 DM in this population. These findings suggest that FABP2 does not represent a major gene for Type 2 DM in this migrant Indian population living in Guadeloupe, but seems to be related to the metabolic insulin resistance syndrome.

Interferon lambda 4 (IFNL4) gene polymorphism is associated with spontaneous clearance of HCV in HIV-1 positive patients.

PubMed

Alves, Camila Fernanda da Silveira; Grott, Camila Schultz; Lunge, Vagner Ricardo; Béria, Jorge Umberto; Tietzmann, Daniela Cardoso; Stein, Airton Tetelbom; Simon, Daniel

2016-01-01

Approximately one-third of the individuals infected with human immunodeficiency virus type 1 (HIV-1) are co-infected with hepatitis C virus (HCV). Co-infected patients have an increased risk for developing end-stage liver diseases. Variants upstream of the IFNL3 gene have been associated with spontaneous and treatment-induced clearance of HCV infection. Recently, a novel polymorphism was discovered, denoted IFNL4 ΔG > TT (rs368234815), which seems to be a better predictor of spontaneous clearance than the IFNL4 rs12979860 polymorphism. We aimed to determine the prevalence of the IFNL4 ΔG > TT variants and to evaluate the association with spontaneous clearance of HCV infection in Brazilian HIV-1 patients. The IFNL4 ΔG > TT genotypes were analyzed by polymerase chain reaction followed by restriction digestion in 138 HIV-1 positive patients who had an anti-HCV positive result. Spontaneous clearance of HCV was observed in 34 individuals (24.6%). IFNL4 genotype distribution was significantly different between individuals who had spontaneous clearance and chronic HCV patients (p=0.002). The probability of spontaneous clearance of HCV infection for patients with the IFNL4 TT/TT genotype was 3.6 times higher than for patients carrying the IFNL4 ΔG allele (OR=3.63, 95% CI:1.51-8.89, p=0.001). The IFNL4 ΔG > TT polymorphism seems to be better than IFNL4 rs12979860 to predict spontaneous clearance of the HCV in Brazilian HIV-1 positive patients.

Gender-related association of AGT gene variants (M235T and T174M) with essential hypertension--a case-control study.

PubMed

Mohana, Vamsi U; Swapna, N; Surender, Reddy S; Vishnupriya, S; Padma, Tirunilai

2012-01-01

The human angiotensinogen (AGT) is a promising candidate gene for evaluating susceptibility to essential hypertension (EH). We aimed to assess the association of the variants of AGT gene and the extent of risk involved in developing EH. A case-control study was designed to compare 279 hypertensive patients with 200 normotensive subjects. The frequency distribution of M235T and T174M polymorphisms of AGT gene was assessed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. A haplotype analysis was done to determine the risk conferred by the combination of alleles of the two polymorphisms for EH. The genotype distribution of the T174M variant differed significantly between hypertensives and normotensives, whereas genotypes of M235T variant did not show such difference. For M235T, MM genotype conferred an increase in risk for hypertension in women (odds ratios (OR) = 2.82; 95% confidence interval (CI) = 1.22-6.49). For the variant T174M, the TM genotype frequency was elevated in hypertensive females (36.5%) as compared to controls (18.8 %; P = .034). The 174M allele was more prevalent among female hypertensives than among female controls (0.20 vs. 0.12; P = .059). The haplotype analysis showed a significant association for the haplotypes of paired markers (M235 and 174M) with a χ(2) value of 8.037 (P = .045). Our findings suggest that the polymorphic variants of AGT gene-M235T and T174M-show association with hypertension.

A Family-Based Association Study of CYP11A1 and CYP11B1 Gene Polymorphisms With Autism in Chinese Trios.

PubMed

Deng, Hong-Zhu; You, Cong; Xing, Yu; Chen, Kai-Yun; Zou, Xiao-Bing

2016-05-01

Autism spectrum disorder is a group of neurodevelopmental disorders with the higher prevalence in males. Our previous studies have indicated lower progesterone levels in the children with autism spectrum disorder, suggesting involvement of the cytochrome P-450scc gene (CYP11A1) and cytochrome P-45011beta gene (CYP11B1) as candidate genes in autism spectrum disorder. The aim of this study was to investigate the family-based genetic association between single-nucleotide polymorphisms, rs2279357 in the CYP11A1 gene and rs4534 and rs4541 in the CYP11B1 gene and autism spectrum disorder in Chinese children, which were selected according to the location in the coding region and 5' and 3' regions and minor allele frequencies of greater than 0.05 in the Chinese populations. The transmission disequilibrium test and case-control association analyses were performed in 100 Chinese Han autism spectrum disorder family trios. The genotype and allele frequency of the 3 single-nucleotide polymorphisms had no statistical difference between the children with autism spectrum disorder and their parents (P> .05). Transmission disequilibrium test analysis showed transmission disequilibrium of CYP11A1 gene rs2279357 single-nucleotide polymorphisms (χ(2)= 5.038,P< .001). Our findings provide further support for the hypothesis that a susceptibility gene for autism spectrum disorder exists within or near the CYP11A1 gene in the Han Chinese population. © The Author(s) 2015.

The impact of ACE gene polymorphism on the incidence and phenotype of sarcoidosis in rural and urban settings.

PubMed

Kieszko, Robert; Krawczyk, Paweł; Powrózek, Tomasz; Szudy-Szczyrek, Aneta; Szczyrek, Michał; Homa, Iwona; Daniluk, Jadwiga; Milanowski, Janusz

2016-12-01

Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Current theory on the etiology of this disease involves participation of genetic factors and unknown antigens present in the patients' environment. The aim of the study was to evaluate the prevalence of different polymorphic forms of the ACE gene in healthy individuals and sarcoidosis patients, and to estimate the risk of sarcoidosis in carriers of different ACE genotypes living in rural and urban settings. The study group included 180 patients with pulmonary sarcoidosis. Assessment of the disease was based on clinical features, laboratory and imaging examinations, as well as bronchoscopy with bronchoalveolar lavage (BAL). ACE gene polymorphism was examined in DNA isolated from peripheral blood or BAL fluid (BALF) leukocytes. Incidence of sarcoidosis was not influenced by gender, age or place of residence of the patients. There were no differences in the frequency of particular genotypes in patients with sarcoidosis and in healthy individuals. The risk of disease did not depend on the ACE gene polymorphism. There were no differences in the frequencies of the different genotypes and alleles of the ACE gene in patients with sarcoidosis divided by gender, age and place of residence or by clinical manifestation of sarcoidosis. Our results do not support the previous concept which suggested a higher incidence of sarcoidosis in individuals living in rural areas and in carriers of selected ACE genotypes. It is possible that this is related to the changing environment of rural areas, increasing urbanization and pollution.

The Influence of C3435T Polymorphism of the ABCB1 Gene on Genetic Susceptibility to Depression and Treatment Response in Polish Population - Preliminary Report.

PubMed

Jeleń, Agnieszka Maria; Sałagacka, Aleksandra; Żebrowska, Marta Karolina; Mirowski, Marek; Talarowska, Monika; Gałecki, Piotr; Balcerczak, Ewa Izabela

2015-01-01

Despite the high prevalence of depression, the mechanism of the origin of this disease as well as the causes of resistance to therapy in some patients are still not fully understood. Increasingly, the possible role of genetic factors is considered. One of them is polymorphisms in the ABCB1 (MDR1) gene which encodes P-glycoprotein, responsible for the transport of xenobiotics, including antidepressant drugs, through the blood-brain barrier. C3435T was evaluated in 90 patients with recurrent depressive disorders (rDD). Genotyping was performed using a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The obtained results indicate that the TT genotype occurred more frequently among patients with rDD than in healthy volunteers (p=0.0441). Also, at least one C allele was present significantly less frequent in the study group than in healthy individuals (p=0.0300). The severity of depressive symptoms was higher among patient with the CC genotype in comparison with the other genotypes (p=0.0106) but treatment response to antidepressants was better in this group than among patients with CT or TT genotypes (p=0.0301). Likewise, patients with the T allele have a significantly lower severity of symptoms (p=0.0026) and decreased therapy effectiveness (p=0.0142) than C allele carriers. This study suggests that C3435T polymorphisms in the ABCB1 gene are strongly associated with a predisposition to depression development, the severity of depressive symptoms and the effectiveness of therapy with using different groups of antidepressant agents.

Relationship between GSTM1 and GSTT1 polymorphisms and schizophrenia: a case-control study in a Tunisian population.

PubMed

Raffa, Monia; Lakhdar, Ramzi; Ghachem, Meriem; Barhoumi, Sana; Safar, Mohamed Taher; Bel Hadj Jrad, Besma; Haj Khelil, Amel; Kerkeni, Abdelhamid; Mechri, Anwar

2013-01-10

There is substantial evidence found in the literature that supports the fact that the presence of oxidative stress may play an important role in the pathophysiology of schizophrenia. The glutathione S-transferases (GSTs) forms one of the major detoxifying groups of enzymes responsible for eliminating products of oxidative stress. Interindividual differences observed in the metabolism of xenobiotics have been attributed to the genetic polymorphism of genes coding for enzymes involved in detoxification. Thus, in this study we investigated the association of glutathione S-transferase Mu-1 (GSTM1) and glutathione S-transferase theta-1 (GSTT1) gene deletion polymorphisms and schizophrenia in a Tunisian population. A case-control study including 138 schizophrenic patients and 123 healthy controls was enrolled. The GSTM1 and GSTT1 polymorphisms were analyzed by multiplex polymerase chain reaction (PCR). No association was found between the GSTM1 genotype and schizophrenia, whereas the prevalence of the GSTT1 active genotype was significantly higher in the schizophrenic patients (57.2%) than in the controls (45.5%) with (OR=0.6, IC 0.37-0.99, p=0.039). Thus, we noted a significant association between schizophrenia and GSTT1 active genotype. Furthermore, the combination of the GSTM1 and GSTT1 null genotypes showed a non-significant trend to an increased risk of schizophrenia. The present finding indicated that GSTT1 seems to be a candidate gene for susceptibility to schizophrenia in at least Tunisian population. Copyright © 2012 Elsevier B.V. All rights reserved.

Differences in MCT1 A1470T polymorphism prevalence between runners and swimmers.

PubMed

Ben-Zaken, S; Eliakim, A; Nemet, D; Rabinovich, M; Kassem, E; Meckel, Y

2015-06-01

Skeletal muscle is the major producer and user of lactate in the body. Therefore, transport of lactate across cells' membrane is of considerable importance. Lactate transport is mediated by proton-linked monocarboxylate transporter (MCT1). The A1470T polymorphism (rs1049434) in MCT1 gene influences lactate transport, with T allele associated with reduction of lactate transport rate and elevation in blood lactate levels. The aim of the current study was to compare allelic and genotype frequencies of MCT1 A1470T polymorphism among Israeli track-and-field athletes, swimmers, and non-athletes. Genomic DNA was extracted from 173 track-and-field athletes (age 17-50), 80 swimmers (age 16-49), and 128 non-athletes (age 19-29). Track-and-field athletes were assigned to three subgroups: long-distance runners, middle-distance runners, and power event athletes. Swimmers were assigned to two subgroups: long-distance swimmers and short-distance swimmers. Genotyping was performed using polymerase chain reaction. T-allele frequency was significantly higher among long-distance swimmers (45%) compared with long- and middle-distance runners (27% and 30%, respectively; P < 0.01). In addition, T-allele frequency was significantly higher among short-distance swimmers (40%) compared with power event athletes (25%, P < 0.01). Overall, T-allele frequency was significantly higher among swimmers (42%) compared with runners (27%, P < 0.001). More research is needed to clarify whether this polymorphism displays advantage for swimming performance. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The mitochondrial superoxide dismutase A16V polymorphism in the cardiomyopathy associated with hereditary haemochromatosis.

PubMed

Valenti, L; Conte, D; Piperno, A; Dongiovanni, P; Fracanzani, A L; Fraquelli, M; Vergani, A; Gianni, C; Carmagnola, L; Fargion, S

2004-12-01

The A16V mitochondrial targeting sequence polymorphism influences the antioxidant activity of MnSOD, an enzyme involved in neutralising iron induced oxidative stress. Patients with hereditary haemochromatosis develop parenchymal iron overload, which may lead to cirrhosis, diabetes, hypogonadism, and heart disease. The objective of this study was to determine in patients with haemochromatosis whether the presence of the Val MnSOD allele, associated with reduced enzymatic activity, affects tissue damage, and in particular heart disease, as MnSOD knockout mice develop lethal cardiomyopathy. We studied 217 consecutive unrelated probands with haemochromatosis, and 212 healthy controls. MnSOD polymorphism was evaluated by restriction analysis. The frequency distribution of the polymorphism did not differ between patients and controls. Patients carrying the Val allele had higher prevalence of cardiomyopathy (A/A 4%, A/V 11%, V/V 30%, p = 0.0006) but not of cirrhosis, diabetes, or hypogonadism, independently of age, sex, alcohol misuse, diabetes, and iron overload (odds ratio 10.1 for V/V, p = 0.006). The frequency of the Val allele was higher in patients with cardiomyopathy (0.67 v 0.45, p = 0.003). The association was significant in both C282Y+/+ (p = 0.02), and in non-C282Y+/+ patients (p = 0.003), and for both dilated (p = 0.01) and non-dilated stage (p = 0.04) cardiomyopathy, but not for ischaemic heart disease. In patients with hereditary haemochromatosis, the MnSOD genotype affects the risk of cardiomyopathy related to iron overload and possibly to other known and unknown risk factors and could represent an iron toxicity modifier gene.

The gender-specific association of rs334558 in GSK3β with major depressive disorder.

PubMed

Liu, Sha; Wang, Le; Sun, Ning; Yang, Chunxia; Liu, Zhifen; Li, Xinrong; Cao, Xiaohua; Xu, Yong; Zhang, Kerang

2017-01-01

Major depressive disorder (MDD) is one of the most prevalent psychiatric illnesses with a heritability ranging from 40% to 50%. The single nucleotide polymorphism (SNP) rs334558 on the glycogen synthase kinase-3β (GSK3β) gene has been identified as a genetic risk loci associated with schizophrenia and bipolar disorder. However, results from replication studies examining the association between rs334558 and MDD remain inconsistent.In the present study, first, we conducted a meta-analysis of the association between rs334558 and MDD by combining 5 available case-control samples totaling 2311 cases and 2535 controls. Second, genotyping data from patients with MDD at our institution, after further stratification by gender, were analyzed to determine the association between rs334558 and MDD.All studies retrieved and included in the meta-analysis were from Korea and China. The meta-analysis suggested that the functional polymorphism rs334558 within the GSK3β promoter region was associated with MDD risk (P < 0.05). The associations were observed both in the allelic and genetic models. Analysis of the genotyping data extracted from our hospital database revealed that rs334558 exhibited exclusive association with MDD in female patients (P=0.015).Our findings suggest that GSK3β rs334558 polymorphisms might be a potential risk for MDD, and females with GSK3β rs334558 polymorphisms might have higher penetrance of MDD. If validated in larger scale samples and in different ethnic populations, these findings might be of value as diagnostic references for MDD.

Interferon lambda 4 (IFNL4) gene polymorphism is associated with spontaneous clearance of HCV in HIV-1 positive patients

PubMed Central

Alves, Camila Fernanda da Silveira; Grott, Camila Schultz; Lunge, Vagner Ricardo; Béria, Jorge Umberto; Tietzmann, Daniela Cardoso; Stein, Airton Tetelbom; Simon, Daniel

2016-01-01

Abstract Approximately one-third of the individuals infected with human immunodeficiency virus type 1 (HIV-1) are co-infected with hepatitis C virus (HCV). Co-infected patients have an increased risk for developing end-stage liver diseases. Variants upstream of the IFNL3 gene have been associated with spontaneous and treatment-induced clearance of HCV infection. Recently, a novel polymorphism was discovered, denoted IFNL4 ΔG > TT (rs368234815), which seems to be a better predictor of spontaneous clearance than the IFNL4 rs12979860 polymorphism. We aimed to determine the prevalence of the IFNL4 ΔG > TT variants and to evaluate the association with spontaneous clearance of HCV infection in Brazilian HIV-1 patients. The IFNL4 ΔG > TT genotypes were analyzed by polymerase chain reaction followed by restriction digestion in 138 HIV-1 positive patients who had an anti-HCV positive result. Spontaneous clearance of HCV was observed in 34 individuals (24.6%). IFNL4 genotype distribution was significantly different between individuals who had spontaneous clearance and chronic HCV patients (p=0.002). The probability of spontaneous clearance of HCV infection for patients with the IFNL4 TT/TT genotype was 3.6 times higher than for patients carrying the IFNL4 ΔG allele (OR=3.63, 95% CI:1.51-8.89, p=0.001). The IFNL4 ΔG > TT polymorphism seems to be better than IFNL4 rs12979860 to predict spontaneous clearance of the HCV in Brazilian HIV-1 positive patients. PMID:27560987

Genetic polymorphisms of the drug-metabolizing enzyme cytochrome P450 3A5 in a Uyghur Chinese population.

PubMed

Chen, Zhengshuai; Li, Jingjie; Chen, Peng; Wang, Fengjiao; Zhang, Ning; Yang, Min; Jin, Tianbo; Chen, Chao

2016-09-01

1.  Detection of CYP3A5 variant alleles, and knowledge about their allelic frequency in Uyghur ethnic groups, is important to establish the clinical relevance of screening for these polymorphisms to optimize pharmacotherapy. 2. We used DNA sequencing to investigate the promoter, exons and surrounding introns, and 3'-untranslated region of the CYP3A5 gene in 96 unrelated healthy Uyghur individuals. We also used SIFT and PolyPhen-2 to predict the protein function of the novel non-synonymous mutation in CYP3A5 coding regions. 3. We found 24 different CYP3A5 polymorphisms in the Uyghur population, three of which were novel: the synonymous mutation 43C > T in exon 1, two mutations 32120C > G and 32245T > C in 3'-untranslated region, and we detected the allele frequencies of CYP3A5*1 and *3 as 64.58% and 35.42%, respectively. While no subjects with CYP3A5*6 were identified. Other identified genotypes included the heterozygous genotype 1A/3A (59.38%) and 1A/3E (11.46%), which lead to decreased enzyme activity. In addition, the frequency of haplotype "TTAGGT" was the most prevalent with 0.781. 4. Our data provide new information regarding CYP3A5 genetic polymorphisms in Uyghur individuals, which may help to improve individualization of drug therapy and offer a preliminary basis for more rational use of drugs.

The GLUT-1 XbaI gene polymorphism is associated with vascular calcifications in nondiabetic uremic patients.

PubMed

Rufino, Margarita; Hernández, Domingo; Barrios, Ysamar; Salido, Eduardo

2008-01-01

Glucose transporters mediate the facilitative uptake of glucose into cells, with GLUT-1 being the predominant isoform in vascular smooth muscle cell (VSMC). Clones of human cells overexpressing the GLUT-1 transporter showed a high increase in intracellular glucose concentrations, mimicking the diabetic milieu. It is possible that high intracellular glucose together with uremic factors may play an important role in vascular calcification by transforming VSMC into osteoblast-like cells. The XbaI polymorphism in the GLUT-1 gene has been linked to variations in GLUT-1 expression, with consequent changes in intracellular glucose concentration. To assess the association between the GLUT-1 XbaI gene polymorphism and the presence of VC in nondiabetic uremic patients, a total of 105 nondiabetic patients on hemodialysis were studied. VC were evaluated by conventional simple X-ray. Mean values of serum calcium, phosphorous, cholesterol, triglycerides, HbA1c, PTH and insulin were measured. Height, weight, BMI and waist circumference were also determined. The GLUT-1 XbaI polymorphism in the second intron of the gene was ascertained by means of the polymerase chain reaction and restriction fragment length polymorphism analysis on DNA isolated from peripheral blood DNA. In the absence of an XbaI site, a fragment of 305 bp was seen (so-called x allele), whereas fragments of 232 and 73 bp were generated if the XbaI site was present (X allele). Genotype distribution in all patients was similar to the Caucasian population. However, when the patients were grouped according to the presence or absence of VC, there were marked differences in the frequency of the GLUT1 genotypes: the xx GLUT-1 genotype was more prevalent in the group with VC (30.7 vs. 4.5%, p = 0.001). Stepwise logistic regression demonstrated that the xx GLUT-1 genotype was independently associated with the presence of VC after adjusting for other variables such as age, calcium x phosphrus product, BMI and time on dialysis (OR 7.68; 95% CI 1.28-45.7). GLUT-1 XbaI gene polymorphism is associated with vascular calcifications in nondiabetic uremic patients. Copyright 2008 S. Karger AG, Basel.

Most Enterobacter aerogenes Strains in France Belong to a Prevalent Clone

PubMed Central

Bosi, Claude; Davin-Regli, Anne; Bornet, Charleric; Mallea, Monique; Pages, Jean-Marie; Bollet, Claude

1999-01-01

The aim of this study was to determine the distribution in France of the Enterobacter aerogenes prevalent clone isolated in the hospitals of the Marseille area (A. Davin-Regli, D. Monnet, P. Saux, C. Bosi, R. Charrel, A. Barthelemy, and C. Bollet, J. Clin. Microbiol. 34:1474–1480, 1996). A total of 123 E. aerogenes isolates were collected from 23 hospital laboratories and analyzed by random amplification of polymorphic DNA and enterobacterial repetitive intergenic consensus-PCR to determine their epidemiological relatedness. Molecular typing revealed that 21 of the 23 laboratories had isolated this prevalent clone harboring the plasmid encoding for extended-spectrum β-lactamase of the TEM-24 type. Most isolates were susceptible only to imipenem and gentamicin. Their dissemination seems to be clonal and was probably the result of the general use of broad-spectrum cephalosporins and quinolones. Four isolates showed an alteration of their outer membrane proteins, causing decrease of susceptibility to third-generation cephalosporins and imipenem and leading to the critical situation of having no alternative therapeutic. The large dissemination of the E. aerogenes prevalent clone probably results from its good adaptation to the antibiotics administered in France and the hospital environment, particularly in intensive care units. PMID:10364580

Prevalence of etravirine mutations and impact on response to treatment in routine clinical care: the Swiss HIV Cohort Study (SHCS).

PubMed

Scherrer, A U; Hasse, B; von Wyl, V; Yerly, S; Böni, J; Bürgisser, P; Klimkait, T; Bucher, H C; Ledergerber, B; Günthard, H F

2009-11-01

Etravirine (ETV) is a novel nonnucleoside reverse transcriptase inhibitor (NNRTI) with reduced cross-resistance to first-generation NNRTIs, which has been primarily studied in randomized clinical trials and not in routine clinical settings. ETV resistance-associated mutations (RAMs) were investigated by analysing 6072 genotypic tests. The antiviral activity of ETV was predicted using different interpretation systems: International AIDS Society-USA (IAS-USA), Stanford, Rega and Agence Nationale de Recherches sur le Sida et les hépatites virales (ANRS). The prevalence of ETV RAMs was higher in NNRTI-exposed patients [44.9%, 95% confidence interval (CI) 41.0-48.9%] than in treatment-naïve patients (9.6%, 95% CI 8.5-10.7%). ETV RAMs in treatment-naïve patients mainly represent polymorphism, as prevalence estimates in genotypic tests for treatment-naïve patients with documented recent (<1 year) infection, who had acquired HIV before the introduction of NNRTIs, were almost identical (9.8%, 95% CI 3.3-21.4). Discontinuation of NNRTI treatment led to a marked drop in the detection of ETV RAMs, from 51.7% (95% CI 40.8-62.6%) to 34.5% (95% CI 24.6-45.4%, P=0.032). Differences in prevalence among subtypes were found for V90I and V179T (P<0.001). Estimates of restricted virological response to ETV varied among algorithms in patients with exposure to efavirenz (EFV)/nevirapine (NVP), ranging from 3.8% (95% CI 2.5-5.6%) for ANRS to 56.2% (95% CI 52.2-60.1%) for Stanford. The predicted activity of ETV decreased as the sensitivity of potential optimized background regimens decreased. The presence of major IAS-USA mutations (L100I, K101E/H/P and Y181C/I/V) reduced the treatment response at week 24. Most ETV RAMs in drug-naïve patients are polymorphisms rather than transmitted RAMs. Uncertainty regarding predictions of antiviral activity for ETV in NNRTI-treated patients remains high. The lowest activity was predicted for patients harbouring extensive multidrug-resistant viruses, thus limiting ETV use in those who are most in need.

Plasmodium diversity in non-malaria individuals from the Bioko Island in Equatorial Guinea (West Central-Africa)

PubMed Central

Guerra-Neira, Ana; Rubio, José M; Royo, Jesús Roche; Ortega, Jorge Cano; Auñón, Antonio Sarrión; Diaz, Pedro Berzosa; LLanes, Agustín Benito

2006-01-01

Background In this paper we analyse the Plasmodium sp. prevalence in three villages with different isolation status on the island of Bioko (Equatorial Guinea) where malaria is a hyper-endemic disease. We also describe the genetic diversity of P. falciparum, using several plasmodia proteins as markers which show a high degree of polymorphism (MSP-1 and MSP-2). The results obtained from three different populations are compared in order to establish the impact of human movements and interventions. Methods Plasmodium sp. were analysed in three villages on Bioko Island (Equatorial Guinea), one of which (Southern) is isolated by geographical barriers. The semi-nested multiplex polymerase chain reaction (PCR) technique was used to determine the prevalence of the four human plasmodia species. The genotyping and frequency of P. falciparum populations were determined by PCR assay target polymorphism regions of the merozoite surface proteins 1 and 2 genes (MSP-1 and MSP-2). Results The data obtained show that there are no differences in plasmodia population flow between the Northwest and Eastern regions as regards the prevalence of the different Plasmodium species. The Southern population, on the other hand, shows a minor presence of P. malariae and a higher prevalence of P. ovale, suggesting some kind of transmission isolated from the other two. The P. falciparum genotyping in the different regions points to a considerable allelic diversity in the parasite population on Bioko Island, although this is somewhat higher in the Southern region than the others. There was a correlation between parasitaemia levels and the age of the individual with the multiplicity of infection (MOI). Conclusion Results could be explained by the selection of particular MSP alleles. This would tend to limit diversity in the parasite population and leading up to the extinction of rare alleles. On the other hand, the parasite population in the isolated village has less outside influence and the diversity of P. falciparum is maintained higher. The knowledge of parasite populations and their relationships is necessary to study their implications for control intervention. PMID:16784527

Return of chloroquine sensitivity to Africa? Surveillance of African Plasmodium falciparum chloroquine resistance through malaria imported to China.

PubMed

Lu, Feng; Zhang, Meihua; Culleton, Richard L; Xu, Sui; Tang, Jianxia; Zhou, Huayun; Zhu, Guoding; Gu, Yaping; Zhang, Chao; Liu, Yaobao; Wang, Weiming; Cao, Yuanyuan; Li, Julin; He, Xinlong; Cao, Jun; Gao, Qi

2017-07-26

Chloroquine (CQ) was the cornerstone of anti-malarial treatment in Africa for almost 50 years, but has been widely withdrawn due to the emergence and spread of resistance. Recent reports have suggested that CQ-susceptibility may return following the cessation of CQ usage. Here, we monitor CQ sensitivity and determine the prevalence of genetic polymorphisms in the CQ resistance transporter gene (pfcrt) of Plasmodium falciparum isolates recently imported from Africa to China. Blood samples were collected from falciparum malaria patients returning to China from various countries in Africa. Isolates were tested for their sensitivity to CQ using the SYBR Green I test ex vivo, and for a subset of samples, in vitro following culture adaptation. Mutations at positions 72-76 and codon 220 of the pfcrt gene were analyzed by sequencing and confirmed by PCR-RFLP. Correlations between drug sensitivity and pfcrt polymorphisms were investigated. Of 32 culture adapted isolates assayed, 17 (53.1%), 6 (18.8%) and 9 (28.1%) were classified as sensitive, moderately resistant, and highly resistant, respectively. In vitro CQ susceptibility was related to point mutations in the pfcrt gene, the results indicating a strong association between pfcrt genotype and drug sensitivity. A total of 292 isolates were typed at the pfcrt locus, and the prevalence of the wild type (CQ sensitive) haplotype CVMNK in isolates from East, South, North, West and Central Africa were 91.4%, 80.0%, 73.3%, 53.3% and 51.7%, respectively. The only mutant haplotype observed was CVIET, and this was almost always linked to an additional mutation at A220S. Our results suggest that a reduction in drug pressure following withdrawal of CQ as a first-line drug may lead to a resurgence in CQ sensitive parasites. The prevalence of wild-type pfcrt CQ sensitive parasites from East, South and North Africa was higher than from the West and Central areas, but this varied greatly between countries. Further surveillance is required to assess whether the prevalence of CQ resistant parasites will continue to decrease in the absence of widespread CQ usage.

Genetic Variants of APOC3 Promoter and HLA-B Genes in an HIV Infected Cohort in Northern South Africa: A Pilot Study

PubMed Central

Masebe, Tracy; Bessong, Pascal Obong; Ndip, Roland Ndip; Meyer, Debra

2014-01-01

Metabolic disorders and hypersensitivities affect tolerability and impact adherence to highly active antiretroviral therapy (HAART). The aim of this study was to determine the prevalence of C-482T/T-455C variants in the Apolipoprotein C3 (APOC3) promoter gene and Human leukocyte antigen (HLA)-B*57:01, known to impact lipid metabolic disorders and hypersensitivity respectively; and to correlate genotypes with gender, CD4+ cell count and viral load in an HIV infected cohort in northern South Africa. Frequencies of C-482 and T-455 polymorphisms in APOC3 were determined by restriction fragment length polymorphism analysis. Allele determination for HLA-B was performed with Assign SBT software in an HLA library. Analysis of APOC3 C-482 site revealed a prevalence of 196/199 (98.5%) for CC, 1/199 (0.5%) for CT and 2/199 (1.0%) for TT genotype (p = 0.000 with 1° of freedom; χ2 = 126.551). For the T-455 site, prevalences were: 69/199 (35%) for TT and 130/199 (65%) for the CC genotype (p = 0.000 with 1° of freedom; χ2 = 199). There was no association between gender and the presence of −482 (p = 1; χ2 = 0.00001) or −455 genotypes (p = 0.1628; χ2 = 1.9842). There was no significant difference in the increase in CD4+ cell count irrespective of genotypes. Significant increases in CD4+ cell count were observed in males and females considering the −455C genotype, but not in males for the −455T genotype. Viral load decreases were significant with the −455C and −482C genotypes irrespective of gender. HLA-B*57:01 was not identified in the study cohort. The apparently high prevalence of APOC3 T-455CC genotype needs confirmation with a larger samples size and triglyceride measurements to support screening of patients to pre-empt HAART associated lipid disorders. PMID:24972136

ApoE and SNAP-25 Polymorphisms Predict the Outcome of Multidimensional Stimulation Therapy Rehabilitation in Alzheimer's Disease.

PubMed

Guerini, Franca Rosa; Farina, Elisabetta; Costa, Andrea Saul; Baglio, Francesca; Saibene, Francesca Lea; Margaritella, Nicolò; Calabrese, Elena; Zanzottera, Milena; Bolognesi, Elisabetta; Nemni, Raffaello; Clerici, Mario

2016-10-01

Alzheimer's disease (AD) is a highly prevalent neurodegenerative disorder. Rate of decline and functional restoration in AD greatly depend on the capacity for neural plasticity within residual neural tissues; this is at least partially influenced by polymorphisms in genes that determine neural plasticity, including Apolipoprotein E4 (ApoE4) and synaptosomal-associated protein of 25 kDa (SNAP-25). We investigated whether correlations could be detected between polymorphisms of ApoE4 and SNAP-25 and the outcome of a multidimensional rehabilitative approach, based on cognitive stimulation, behavioral, and functional therapy (multidimensional stimulation therapy [MST]). Fifty-eight individuals with mild-to-moderate AD underwent MST for 10 weeks. Neuro-psychological functional and behavioral evaluations were performed blindly by a neuropsychologist at baseline and after 10 weeks of therapy using Mini-Mental State Examination (MMSE), Functional Living Skill Assessment (FLSA), and Neuropsychiatric Inventory (NPI) scales. Molecular genotyping of ApoE4 and SNAP-25 rs363050, rs363039, rs363043 was performed. Results were correlated with ΔMMSE, ΔNPI and ΔFLSA scores by multinomial logistic regression analysis. Polymorphisms in both genes correlated with the outcome of MST for MMSE and NPI scores. Thus, higher overall MMSE scores after rehabilitation were detected in ApoE4 negative compared to ApoE4 positive patients, whereas the SNAP-25 rs363050(G) and rs363039(A) alleles correlated with significant improvements in behavioural parameters. Polymorphisms in genes known to modulate neural plasticity might predict the outcome of a multistructured rehabilitation protocol in patients with AD. These data, although needing confirmation on larger case studies, could help optimizing the clinical management of individuals with AD, for example defining a more intensive treatment in those subjects with a lower likelihood of success. © The Author(s) 2016.

Associations of the eNOS G894T gene polymorphism with target organ damage in children with newly diagnosed primary hypertension.

PubMed

Śladowska-Kozłowska, Joanna; Litwin, Mieczysław; Niemirska, Anna; Wierzbicka, Aldona; Roszczynko, Marta; Szperl, Małgorzata

2015-12-01

The endothelial nitric oxide synthase (eNOS) G894T gene polymorphism is associated with the risk of primary hypertension (PH) and vascular complications in adults with PH. We explored the associations of the G894T polymorphism with 24-h ambulatory blood pressure, left ventricular mass (LVM), carotid intima media thickness (cIMT), urinary albumin excretion, oxidative stress and inflammatory parameters in 126 children with newly diagnosed PH and in 83 healthy children. Among the 126 children with PH 92 (73%) had ambulatory hypertension and 34 (27%) had severe ambulatory hypertension. Left ventricular hypertrophy (LVH) was detected in 39 (31%) patients, cIMT of >2 standard deviation scores in 21 (16.6%) patients, albuminuria of >30 mg/24 h in 18 (14.3%) patients and metabolic syndrome (MS) in 22 (17.5%) patients. The frequency of the T allele was 52.4% in the PH group and 54.2% in the control group (not significant), and in both groups the frequency of the T allele was consistent with the Hardy-Weinberg equilibrium. Compared with G allele carriers, hypertensive T allele carriers had increased cIMT (p < 0.05) and more severe albuminuria (not significant, p = 0.1); there was no difference between the groups in hypertension severity and LVM. T and G allele distribution did not differ between patients with and without metabolic syndrome. No significant correlations between the assessed parameters and the eNOS G894T gene polymorphism were found in the controls, although T allele carriers tended to have an increased cIMT (p = 0.09). The eNOS T allele is not more prevalent among hypertensive children than among healthy ones, but it is associated with early vascular damage in children with PH, independent of metabolic abnormalities. No associations between the eNOS G894T polymorphism and metabolic abnormalities were found.

Association of Allelic Interaction of Single Nucleotide Polymorphisms of Influx and Efflux Transporters Genes With Nonhematologic Adverse Events of Docetaxel in Breast Cancer Patients.

PubMed

Jabir, Rafid Salim; Ho, Gwo Fuang; Annuar, Muhammad Azrif Bin Ahmad; Stanslas, Johnson

2018-05-04

Nonhematologic adverse events (AEs) of docetaxel constitute an extra burden in the treatment of cancer patients and necessitate either a dose reduction or an outright switch of docetaxel for other regimens. These AEs are frequently associated with genetic polymorphisms of genes encoding for proteins involved docetaxel disposition. Therefore, we investigated that association in Malaysian breast cancer patients. A total of 110 Malaysian breast cancer patients were enrolled in the present study, and their blood samples were investigated for different single nucleotide polymorphisms using polymerase chain reaction restriction fragment length polymorphism. AEs were evaluated using the Common Terminology Criteria for Adverse Events, version 4.0. Fatigue, nausea, oral mucositis, and vomiting were the most common nonhematologic AEs. Rash was associated with heterozygous and mutant genotypes of ABCB1 3435C>T (P < .05). Moreover, patients carrying the GG genotype of ABCB1 2677G>A/T reported more fatigue than those carrying the heterozygous genotype GA (P < .05). The presence of ABCB1 3435-T, ABCC2 3972-C, ABCC2 1249-G, and ABCB1 2677-G alleles was significantly associated with nausea and oral mucositis. The coexistence of ABCB1 3435-C, ABCC2 3972-C, ABCC2 1249-G, and ABCB1 2677-A was significantly associated with vomiting (P < .05). The prevalence of nonhematologic AEs in breast cancer patients treated with docetaxel has been relatively high. The variant allele of ABCB1 3435C>T polymorphism could be a potential predictive biomarker of docetaxel-induced rash, and homozygous wild-type ABCB1 2677G>A/T might predict for a greater risk of fatigue. In addition, the concurrent presence of specific alleles could be predictive of vomiting, nausea, and oral mucositis. Copyright © 2018 Elsevier Inc. All rights reserved.

GSTP1 Polymorphisms and their Association with Glutathione Transferase and Peroxidase Activities in Patients with Motor Neuron Disease.

PubMed

Gajewska, Beata; Kaźmierczak, Beata; Kuźma-Kozakiewicz, Magdalena; Jamrozik, Zygmunt; Barańczyk-Kuźma, Anna

2015-01-01

Glutathione S-transferase pi (GSTP1) is a crucial enzyme in detoxification of electrophilic compounds and organic peroxides. Together with Se-dependent glutathione peroxidase (Se-GSHPx) it protects cells against oxidative stress which may be a primary factor implicated in motor neuron disease (MND) pathogenesis. We investigated GSTP1 polymorphisms and their relationship with GST and Se-GSTPx activities in a cohort of Polish patients with MND. Results were correlated with clinical phenotypes. The frequency of genetic variants for GSTP1 exon 5 (I105V) and exon 6 (A114V) was studied in 104 patients and 100 healthy controls using real-time polymerase chain reaction. GST transferase activity was determined in serum with 1-chloro-2,4-dinitrobenzene, its peroxidase activity with cumene hydroperoxide, and Se-GSHPx activity with hydrogen peroxide. There were no differences in the prevalence of GSTP1 polymorphism I105V and A114V between MND and controls, however the occurrence of CT variant in codon 114 was associated with a higher risk for MND. GSTP1 polymorphisms were less frequent in classic ALS than in progressive bulbar palsy. In classic ALS C* (heterozygous I /V and A /V) all studied activities were significantly lower than in classic ALS A* (homozygous I /I and A/A). GST peroxidase activity and Se-GSHPx activity were lower in classic ALS C* than in control C*, but in classic ALS A* Se-GSHPx activity was significantly higher than in control A*. It can be concluded that the presence of GSTP1 A114V but not I105V variant increases the risk of MND, and combined GSTP1 polymorphisms in codon 105 and 114 may result in lower protection of MND patients against the toxicity of electrophilic compounds, organic and inorganic hydroperoxides.

Role of TNF-α -308G/A gene polymorphism in gastric cancer risk: A case control study and meta-analysis.

PubMed

Du, Li Chuan; Gao, Ru

2017-07-01

In the Chinese population, gastric cancer (GC) is ranked as the third most common type of cancer. Although the exact etiology of GC development is unclear, several factors, including genetic and environmental, have been identified as risk factors. Variations in cytokine genes and their receptors have been related to a higher risk of GC. A single nucleotide polymorphism in the promoter region of tumor necrosis factor-α (TNF-α) (-308G>A) has been associated with a higher risk of GC and in the present study we evaluated its possible association with GC in a Chinese cohort. In addition, we performed a meta-analysis to draw a firm conclusion about the association between TNF-α gene polymorphisms and GC. We enrolled 400 Chinese GC patients and matched healthy controls hailing from similar geographical areas. The TNF-α -308G/A polymorphism was genotyped by allele-specific polymerase chain reaction (AS-PCR). For the meta-analysis, earlier published articles were searched and eligible studies were included. Prevalence of the heterozygous mutant (GA) and minor allele (A) were significantly higher in GC cases compared to healthy controls (GA: p<0.0001, odds ratio (OR)=4.90; A: p<0.0001, OR=2.84). A total of 36 eligible studies including the present report, encompassing of 8353 GC patients and 12099 controls, were analyzed for the meta-analysis. A significant association of the TNF-α polymorphism (-308G>A) with susceptibility to GC was only found in the Caucasian population (A vs G: p=0.001; AA vs GG: p=0.01; AG vs GG: p<0.0001; AA vs AG+GG: p=0.01; AA+AG vs p=0.003). The results of the present case control study and meta-analysis showed that associations between TNF-a variants with susceptibility to GC development is population and ethnic specific.

Renin angiotensin system blockage associates with insertion/deletion polymorphism of angiotensin-converting enzyme in patients with hypertensive emergency.

PubMed

Vilela-Martin, José F; Vaz-de-Melo, Renan O; Cosenso-Martin, Luciana N; Kuniyoshi, Cristina H; Yugar-Toledo, Juan C; Pinhel, Marcela A S; de Souza, Gisele F; Souza, Dorotéia R S; Pimenta, Eduardo; Moreno, Heitor; Cipullo, José P

2013-09-01

Hypertensive crisis (HC) stands out as a form of acute elevation of blood pressure (BP). It can manifest itself as hypertensive emergency (HE) or hypertensive urgency (HU), which is usually accompanied with levels of diastolic BP ≥120 mmHg. Angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism may influence manifestations of HC. Thus, this study evaluated the influence of ACE I/D polymorphism in individuals with HC. A total of 187 patients admitted with HC (HU [n=69] and HE [n=118]) and 75 normotensive individuals were included in the study. Peripheral blood was drawn for a biochemical and genetic analysis of the ACE I/D polymorphism by Polymerase Chain Reaction. HC group showed higher systolic BP, body mass index (BMI), glycemia, creatinine, and lower high-density lipoprotein (HDL) cholesterol compared with normotensive individuals. The use of renin-angiotensin system (RAS) blockers was more frequent in the HU group than in the HE group (p=0.020). The II genotype was more predominant in normotensive and HU individuals than among HE individuals (18.7%, 11.6%, and 2.5%, respectively; p=0.004). Higher BMI and glycemia were associated with HC in the logistic regression model. ACE II genotype (odds ratio [OR] 0.14; 95% confidence interval [CI] 0.04-0.51) and HDL cholesterol were protective for the development of HE. ACE II genotype was present in the HU group, compared with the HE group (OR 0.18; 95% CI 0.04-0.88). This study shows an association between the low prevalence of ACE I/D polymorphism II genotype and a greater occurrence of HE in Brazilian individuals. The lower blockage of RAS, which was detected in the HE group, may interact with the low frequency of II genotype, conferring an increased risk for HE.

Plasma homocysteine levels, methylene tetrahydrofolate reductase A1298C gene polymorphism and risk of retinal vein thrombosis.

PubMed

Ghaznavi, Habib; Soheili, Zahra; Samiei, Shahram; Soltanpour, Mohammad Soleiman

2016-09-01

There are limited data regarding the role of methylene tetrahydrofolate reductase (MTHFR) A1298C polymorphism and hyperhomocysteinemia as risk factors for retinal vein thrombosis (RVT) in Iranians. This study aimed to examine a possible association between fasting plasma total homocysteine (tHcy) levels, MTHFR A1298C polymorphism and RVT development in Iranian patients. Our study population consisted of 73 patients with a diagnosis of RVT (52.7 ± 16.2 years) and 73 age and sex-matched healthy controls (49.1 ± 14.6 years). Genotyping for the MTHFR A1298Cpolymorphism was conducted by PCR-RFLP technique and plasma tHcy levels were measured by an enzyme immunoassay method. Fasting plasma tHcy levels were 20.29 ± 8.5 μmol/l in RVT patients and 10.9 ± 3.1 μmol/l in control subjects. The number of cases with abnormal tHcy values (hyperhomocysteinemia) was significantly higher in the RVT patients than control subjects (P = 0.0001). The prevalence of MTHFR 1298CC homozygote genotype was similar in RVT patients and controls (17.8 vs.15.1%, P = 0.45). There were no significant differences in genotype distribution of MTHFR A1298C polymorphism between males and females in both RVT patients and controls (P > 0.05). The frequency of the 1298C allele was 39.1 and 35.6% in patients and controls, respectively, and did not differ significantly between them (P = 0.23). Moreover, heterozygote and homozygote genotypes in the RVT patients had significantly higher abnormal tHcy values than corresponding genotypes in control subjects (P < 0.001). Our study demonstrated that hyperhomocysteinemia but not homozygosity for MTHFR A1298C polymorphism is a significant risk factor for RVT in the Iranian population.

Polymorphisms in Plasmodium vivax Circumsporozoite Protein (CSP) Influence Parasite Burden and Cytokine Balance in a Pre-Amazon Endemic Area from Brazil

PubMed Central

Ribeiro, Bruno de Paulo; Cassiano, Gustavo Capatti; de Souza, Rodrigo Medeiros; Cysne, Dalila Nunes; Grisotto, Marcos Augusto Grigolin; de Azevedo dos Santos, Ana Paula Silva; Marinho, Cláudio Romero Farias; Machado, Ricardo Luiz Dantas; Nascimento, Flávia Raquel Fernandes

2016-01-01

Mechanisms involved in severe P. vivax malaria remain unclear. Parasite polymorphisms, parasite load and host cytokine profile may influence the course of infection. In this study, we investigated the influence of circumsporozoite protein (CSP) polymorphisms on parasite load and cytokine profile in patients with vivax malaria. A cross-sectional study was carried out in three cities: São Luís, Cedral and Buriticupu, Maranhão state, Brazil, areas of high prevalence of P. vivax. Interleukin (IL)-2, IL-4, IL-10, IL-6, IL-17, tumor necrosis factor alpha (TNF-α, interferon gamma (IFN-γ and transforming growth factor beta (TGF-β were quantified in blood plasma of patients and in supernatants from peripheral blood mononuclear cell (PBMC) cultures. Furthermore, the levels of cytokines and parasite load were correlated with VK210, VK247 and P. vivax-like CSP variants. Patients infected with P. vivax showed increased IL-10 and IL-6 levels, which correlated with the parasite load, however, in multiple comparisons, only IL-10 kept this association. A regulatory cytokine profile prevailed in plasma, while an inflammatory profile prevailed in PBMC culture supernatants and these patterns were related to CSP polymorphisms. VK247 infected patients showed higher parasitaemia and IL-6 concentrations, which were not associated to IL-10 anti-inflammatory effect. By contrast, in VK210 patients, these two cytokines showed a strong positive correlation and the parasite load was lower. Patients with the VK210 variant showed a regulatory cytokine profile in plasma, while those infected with the VK247 variant have a predominantly inflammatory cytokine profile and higher parasite loads, which altogether may result in more complications in infection. In conclusion, we propose that CSP polymorphisms is associated to the increase of non-regulated inflammatory immune responses, which in turn may be associated with the outcome of infection. PMID:26943639

Aldehyde dehydrogenase 2 polymorphism for development to hepatocellular carcinoma in East Asian alcoholic liver cirrhosis.

PubMed

Abe, Hiroshi; Aida, Yuta; Seki, Nobuyoshi; Sugita, Tomonori; Tomita, Yoichi; Nagano, Tomohisa; Itagaki, Munenori; Sutoh, Satoshi; Nagatsuma, Keisuke; Itoh, Kyoko; Matsuura, Tomokazu; Aizawa, Yoshio

2015-09-01

We aimed to clarify the influences of aldehyde dehydrogenase 2 (ALDH2), alcohol dehydrogenase 1B (ADH1B) polymorphisms, and ethanol consumption profile to hepatocellular carcinoma (HCC) development in alcoholic liver cirrhosis without chronic hepatitis B and C virus infection (non-B non-C). Of 236 freshly diagnosed non-B non-C alcoholic liver cirrhosis patients, 67 were diagnosed as HCC and the remaining 169 as not having HCC. The relationship between the genetic polymorphisms and development to HCC were evaluated in well-matched patients with HCC (HCC group, n = 67) and without HCC (non-HCC group, n = 67) using propensity scores in age, sex, and prevalence of diabetes mellitus. Daily amount of ethanol consumption was significantly lower (P = 0.005), and consumptive period was significantly longer (P = 0.003) in HCC group than non-HCC group. Of 134 well-matched patients, 113 (84.3%) had ALDH2*1/*1 genotype and 21 (15.7%) had ALDH2*1/*2 genotype. In HCC development, consumptive long period (P = 0.007) and carrying ALDH2*1/*2 genotype (P = 0.026) were identified as significant factors independently participated, while there was no relation to ADH1B polymorphism. In addition, consumptive period was significantly longer in HCC group than non-HCC group in ALDH2*1/*1 genotype patients (P = 0.0005), while there was no difference in profile of ethanol consumption in ALDH2*1/*2 genotype patients. Among HCC group, daily (P = 3.78 × 10(-6) ) and cumulative amount (P = 4.89 × 10(-6) ) of ethanol consumption were significantly higher in ALDH2*1/*1 genotype patients than ALDH2*1/*2 genotype patients. In alcoholic liver cirrhosis, investigations of ALDH2 polymorphism and ethanol consumption profile are useful for prediction of HCC development. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

MTHFR (C677T) polymorphism and PR (PROGINS) mutation as genetic factors for preterm delivery, fetal death and low birth weight: A Northeast Indian population based study.

PubMed

Tiwari, Diptika; Bose, Purabi Deka; Das, Somdatta; Das, Chandana Ray; Datta, Ratul; Bose, Sujoy

2015-02-01

Preterm delivery (PTD) is one of the most significant contributors to neonatal mortality, morbidity, and long-term adverse consequences for health; with highest prevalence reported from India. The incidence of PTD is alarmingly very high in Northeast India. The objective of the present study is to evaluate the associative role of MTHFR gene polymorphism and progesterone receptor (PR) gene mutation (PROGINS) in susceptibility to PTD, negative pregnancy outcome and low birth weights (LBW) in Northeast Indian population. A total of 209 PTD cases {extreme preterm (< 28 weeks of gestation, n = 22), very preterm (28-32 weeks of gestation, n = 43) and moderate preterm (32-37 weeks of gestation, n = 144) and 194 term delivery cases were studied for MTHFR C677T polymorphism and PR (PROGINS) gene mutation. Statistical analysis was performed using SPSS software. Distribution of MTHFR and PR mutation was higher in PTD cases. Presence of MTHFR C677T polymorphism was significantly associated and resulted in the increased risk of PTD (p < 0.001), negative pregnancy outcome (p < 0.001) and LBW (p = 0.001); more significantly in extreme and very preterm cases. Presence of PR mutation (PROGINS) also resulted in increased risk of PTD and negative pregnancy outcome; but importantly was found to increase the risk of LBW significantly in case of very preterm (p < 0.001) and moderately preterm (p < 0.001) delivery cases. Both MTHFR C677T polymorphism and PR (PROGINS) mutation are evident genetic risk factors associated with the susceptibility of PTD, negative pregnancy outcome and LBW. MTHFR C677T may be used as a prognostic marker to stratify subpopulation of pregnancy cases predisposed to PTD; thereby controlling the risks associated with PTD.

Association between MTHFR C677T polymorphism and abdominal aortic aneurysm risk

PubMed Central

Liu, Jie; Jia, Xin; Li, Haifeng; Jia, Senhao; Zhang, Minhong; Xu, Yongle; Du, Xin; Zhang, Nianrong; Lu, Weihang; Guo, Wei

2016-01-01

Abstract Background: Abdominal aortic aneurysm (AAA) is a life-threatening condition. A number of studies reported the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and AAA risk, but substantial controversial findings were observed and the strength of the association remains unclear. Objective: The aim of this study was to investigate the aforementioned association in the overall population and different subgroups. Methods: PUBMED and EMBASE databases were searched until March 2016 to identify eligible studies, restricted to humans and articles published in English. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the susceptibility to AAA. Subgroup meta-analyses were conducted on features of the population, such as ethnicity, sex of the participants, and study design (source of control). Results: Twelve case–control studies on MTHFR C677T polymorphism and AAA risk, including 3555 cases and 6568 case-free controls were identified. The results revealed no significant association between the MTHFR C677T polymorphism and AAA risk in the overall population and within Caucasian or Asian subpopulations in all 5 genetic models. Further subgroup meta-analysis indicated that significantly increased risks were observed among cases with a mean age <70 years (OR = 1.73, 95% CI = 1.10–2.12, P = 0.02), cases with prevalence of smoking <60% (OR = 1.39, 95% CI = 1.02–1.90, P = 0.04), and cases with aneurysm diameter ≥55 mm (OR = 1.55, 95% CI = 1.07–2.24, P = 0.02) in the dominant genetic model. No publication bias was detected in the present study. Conclusion: In conclusion, our comprehensive meta-analysis suggests that the MTHFR C677T polymorphism may play an important role in AAA susceptibility, especially in younger, non-smoking, larger AAA-diameter subgroups of patients PMID:27603386

Combination of ALDH2 and ADH1B polymorphisms is associated with smoking initiation: A large-scale cross-sectional study in a Japanese population.

PubMed

Masaoka, Hiroyuki; Ito, Hidemi; Gallus, Silvano; Watanabe, Miki; Yokomizo, Akira; Eto, Masatoshi; Matsuo, Keitaro

2017-04-01

Aldehyde dehydrogenase 2 (ALDH2; rs671, Glu504Lys) and alcohol dehydrogenase 1B (ADH1B; rs1229984, His47Arg) polymorphisms are known to strongly influence alcohol　drinking behavior. Given evidence of an association between smoking and drinking behaviors, we hypothesized that ALDH2/ADH1B polymorphisms might also be associated with smoking initiation, and conducted a cross-sectional study to examine this hypothesis. Study subjects were first-visit outpatients diagnosed not to have cancer at Aichi Cancer Center Hospital between 2001 and 2005, including 4141 never smokers and 2912 ever smokers. Unconditional logistic regression models were applied to estimate odds ratios (OR) and 95% confidence intervals (CI) for smoking initiation by comparing ever smokers with never smokers. Excessive alcohol drinking was associated with a higher likelihood of ever smoking. After adjustment for drinking behaviors, compared to individuals with ALDH2 Glu/Glu, the ORs of ever smoking were 1.71 (95% CI, 1.49-1.95) and 2.28 (1.81-2.87) among those with ALDH2 Glu/Lys and Lys/Lys, respectively. Combination of ALDH2 Lys/Lys and ADH1B His/His (i.e., the most alcohol-intolerant subpopulation) showed the highest OR [2.44 (1.84-3.23)], whereas combination of ALDH2 Glu/Glu and ADH1B Arg/Arg (i.e., the most alcohol-tolerant subpopulation) showed the lowest OR [0.83 (0.57-1.21)] compared with ALDH2 Glu/Glu and ADH1B His/His. Besides the amount and frequency of alcohol drinking, the combination of ALDH2 and ADH1B polymorphisms predicts smoking initiation. This study suggests that alcohol tolerance regulated by ALDH2 and ADH1B polymorphisms is associated with smoking initiation, and facilitates the development of targeted interventions to reduce smoking prevalence. Copyright © 2017 Elsevier B.V. All rights reserved.

Relationship between cardiometabolic profile, vitamin D status and BsmI polymorphism of the VDR gene in non-institutionalized elderly subjects: Cardiometabolic profile, vitamin D status and BsmI polymorphism of the VDR gene in non-institutionalized elderly subjects.

PubMed

Issa, Chahira Taha Mahd Ibrahim; Silva, Alexandre Sérgio; Toscano, Luciana Tavares; Medeiros, Marcia Silva; Persuhn, Darlene Camati; da Silva Diniz, Alcides; de Carvalho Costa, Maria José; Rodrigues Gonçalves, Maria da Conceição

2016-08-01

This study aimed to evaluate the relationship between the cardiometabolic profile, vitamin D status and BsmI polymorphism of the VDR gene in non-institutionalized elderly subjects. A cross-sectional study was conducted with a random and representative sample of 142 elderly subjects selected by cluster and recruited from a municipal assistance program. Clinical, nutritional, biochemical and inflammatory profiles, oxidative stress and genotyping for the BsmI polymorphism were evaluated. Participants had mean age of 69.9 (7.0) years, BMI of 28.3 (4.4) kg/m(2) and 80.3% were women. The prevalence of a 25-hydroxyvitamin D [25(OH)D] status <75nmol/L was 40.8%. A vitamin D level<75nmol/L was found to be associated with gender and fish consumption. The INSUF/DEF group [25(OH)D<75nmol/L] showed higher fasting blood glucose MDA values when compared to the SUF group [25(OH)D≥75nmol/L]; this relationship was maintained only for women in the analysis by sex. The BsmI polymorphism showed allelic frequencies in the SUF group of B 49% and b 51% and in the INSUF/DEF group B 38% and b 62%. The frequency of bb homozygosity was significantly associated with lower serum total cholesterol and LDL cholesterol concentrations compared to Bb, both in the general population and in the SUF group. Among individuals with bb, the INSUF/DEF group showed higher levels of triglycerides and VLDL cholesterol. Blood glucose levels and oxidative stress were increased in elderly subjects with 25(OH)D<75nmol/L. The presence of the bb genotype with adequate vitamin D status resulted in lower total and LDL cholesterol, but the benefit was lost when vitamin D insufficiency or deficiency was present. Copyright © 2016 Elsevier Inc. All rights reserved.

Association of Lactase Persistence Genotypes with High Intake of Dairy Saturated Fat and High Prevalence of Lactase Non-Persistence among the Mexican Population.

PubMed

Ojeda-Granados, Claudia; Panduro, Arturo; Rebello Pinho, João Renato; Ramos-Lopez, Omar; Gleyzer, Ketti; Malta, Fernanda de Mello; Gonzalez-Aldaco, Karina; Roman, Sonia

2016-01-01

Lactase (LCT) -13910 C>T and -22018 G>A polymorphisms associated with the lactase non-persistence (LNP)/persistence (LP) phenotypes vary globally. LP has been associated with obesity in Europeans. However, it has not been genetically evaluated in Mexico, a country with admixed population, recent introduction of dairy, and a high prevalence of obesity. Thus, we aimed to determine the distribution of the LCT polymorphisms and their association with the nutritional profile of West Mexico's populations. Genotyping of 1,196 individuals (natives and mestizos) was carried out by a Taqman allelic discrimination assay. Descriptive statistics and interpopulation analyzes were performed by SPSS, Arlequin, and Structure software. Demographic, anthropometric, biochemical and dietary data were analyzed in 212 mestizos. LNP genotypes mainly prevailed (CC 68.7% and GG 68.2%); both predominated in native Huicholes and Nahuas (>97.7%). Among the mestizos, the LP genotypes were associated with a higher intake of saturated fat (9.9 ± 3.9% vs. 8.5 ± 4.0%, p = 0.018; OR = 2.55, 95% CI 1.29-5.03, p = 0.006) and a daily/more frequent consumption of dairy (88.8 vs. 78.0%; p = 0.049) than LNP genotypes. The LNP trait was predominant in Mexicans with a major Amerindian ancestry. A daily consumption of dairy was associated with a higher intake of saturated fat in LP individuals. © 2016 S. Karger AG, Basel.

Clinical Relevant Polymorphisms Affecting Clopidogrel Pharmacokinetics and Pharmacodynamics: Insights from the Puerto Rico Newborn Screening Program.

PubMed

Hernandez-Suarez, Dagmar F; Tomassini-Fernandini, Jonnalie C; Cuevas, Angelica; Rosario-Berrios, Anyelis N; Nuñez-Medina, Héctor J; Padilla-Arroyo, Dariana; Rivera, Nannette; Liriano, Jennifer; Vega-Roman, Rocio K; Renta, Jessicca Y; Melin, Kyle; Duconge, Jorge

2018-05-30

Background: Variations in several clopidogrel-pharmacogenes have been linked to clopidogrel response variability and clinical outcomes. We aimed to determine the frequency distribution of major polymorphisms on CYP2C19 , PON1 , ABCB1 and P2RY12 pharmacogenes in Puerto Ricans. Methods : This was a cross-sectional, population-based study of 200 unrelated "Guthrie" cards specimens from newborns registered in the Puerto Rican newborn screening program (PRNSP) between 2004 and 2014. Taqman ® SNP assay techniques were used for genotyping. Results: Minor allele frequencies (MAF) were 46% for PON1 (rs662), 41% for ABCB1 (rs1045642), 14% for CYP2C19 *17, 13% for CYP2C19 *2, 12% for P2RY12 -H2 and 0.3% for CYP2C19 *4. No carriers of the CYP2C19 *3 variants were detected. All alleles and genotype proportions were found to be in Hardy⁻Weinberg equilibrium (HWE). Overall, there were no significant differences between MAFs of these variants in Puerto Ricans and the general population ( n = 453) of the 1000 Genome project, except when comparisons to each individual parental group were performed (i.e., Africans, Europeans and East-Asians; p < 0.05). As expected, the prevalence of these markers in Puerto Ricans most resembled those in the 181 subjects from reference populations of the Americas. Conclusions: These prevalence data provide a necessary groundwork for future clinical studies of clopidogrel pharmacogenetics in Caribbean Hispanics.

Racial differences in venous thromboembolism.

PubMed

Zakai, N A; McClure, L A

2011-10-01

The incidence of venous thrombosis (VTE) varies by race, with African-Americans having over 5-fold greater incidence than Asian-ancestry populations, and an intermediate risk for European and Hispanic populations. Known racial differences in genetic polymorphisms associated with thrombosis do not account for this gradient of risk, nor do known racial variations in environmental risk factors. Data on the incidence of and risk factors for VTE outside of Europe and North America and in non-European ancestry populations are sparse. Common genetic polymorphisms in European-Ancestry populations, such as factor V Leiden and prothrombin G20210A, and environmental risk factors, such as obesity, may account for some of the increased risk in European populations, and high factor VIII, high von Willebrand factor and low protein C levels and increased prevalence of obesity may explain some of the increased risk in African-Americans. The low rates in Asian populations may be partially explained by low clinical suspicion in a perceived low-risk population and lack of access to healthcare in other populations. As risk factors for thrombosis, such as surgery and treatment for cancer, are applicable to more people, as obesity increases in prevalence in the developing world, and as surveillance systems for VTE improve, VTE may increase in previously low-risk populations. While differences in VTE by race due to genetic predisposition will probably always be present, understanding the reasons for racial differences in VTE will help providers develop strategies to minimize VTE in all populations. © 2011 International Society on Thrombosis and Haemostasis.

Genomically Intact Endogenous Feline Leukemia Viruses of Recent Origin

PubMed Central

Roca, Alfred L.; Pecon-Slattery, Jill; O'Brien, Stephen J.

2004-01-01

We isolated and sequenced two complete endogenous feline leukemia viruses (enFeLVs), designated enFeLV-AGTT and enFeLV-GGAG. In enFeLV-AGTT, the open reading frames are reminiscent of a functioning FeLV genome, and the 5′ and 3′ long terminal repeat sequences are identical. Neither endogenous provirus is genetically fixed in cats but polymorphic, with 8.9 and 15.2% prevalence for enFeLV-AGTT and enFeLV-GGAG, respectively, among a survey of domestic cats. Neither provirus was found in the genomes of related species of the Felis genus, previously shown to harbor enFeLVs. The absence of mutational divergence, polymorphic incidence in cats, and absence in related species suggest that these enFeLVs may have entered the germ line more recently than previously believed, perhaps coincident with domestication, and reopens the question of whether some enFeLVs might be replication competent. PMID:15047851

Apolipoprotein Eε4: A Biomarker for Executive Dysfunction among Parkinson's Disease Patients with Mild Cognitive Impairment.

PubMed

Samat, Nor A; Abdul Murad, Nor A; Mohamad, Khairiyah; Abdul Razak, Mohd R; Mohamed Ibrahim, Norlinah

2017-01-01

Background: Cognitive impairment is prevalent in Parkinson's disease (PD), affecting 15-20% of patients at diagnosis. α-synuclein expression and genetic polymorphisms of Apolipoprotein E ( ApoE ) have been associated with the presence of cognitive impairment in PD although data have been inconsistent. Objectives: To determine the prevalence of cognitive impairment in patients with PD using Montreal Cognitive Assessment (MoCA), Comprehensive Trail Making Test (CTMT) and Parkinson's disease-cognitive rating scale (PDCRS), and its association with plasma α-synuclein and ApoE genetic polymorphisms. Methods: This was across-sectional study involving 46 PD patients. Patients were evaluated using Montreal cognitive assessment test (MoCA), and detailed neuropsychological tests. The Parkinson's disease cognitive rating scale (PDCRS) was used for cognitive function and comprehensive trail making test (CTMT) for executive function. Blood was drawn for plasma α-synuclein measurements and ApoE genetic analysis. ApoE polymorphism was detected using MutaGEL APoE from ImmunDiagnostik. Plasma α-synuclein was detected using the ELISA Technique (USCN Life Science Inc.) according to the standard protocol. Results: Based on MoCA, 26 (56.5%) patients had mild cognitive impairment (PD-MCI) and 20 (43.5%) had normal cognition (PD-NC). Based on the PDCRS, 18 (39.1%) had normal cognition (PDCRS-NC), 17 (37%) had mild cognitive impairment (PDCRS-MCI), and 11 (23.9%) had dementia (PDCRS-PDD). In the PDCRS-MCI group, 5 (25%) patients were from PD-NC group and all PDCRS-PDD patients were from PD-MCI group. CTMT scores were significantly different between patients with MCI and normal cognition on MoCA ( p = 0.003). Twenty one patients (72.4%) with executive dysfunction were from the PD-MCI group; 17 (77.3%) with severe executive dysfunction and 4 (57.1%) had mild to moderate executive dysfunction. There were no differences in the plasma α-synuclein concentration between the presence or types of cognitive impairment based on MoCA, PDCRS, and CTMT. The ApoEe4 allele carrier frequency was significantly higher in patients with executive dysfunction ( p = 0.014). Conclusion: MCI was prevalent in our PD population. PDCRS appeared to be more discriminatory in detecting MCI and PDD than MoCA. Plasma α-synuclein level was not associated with presence nor type of cognitive impairment, but the ApoEe4 allele carrier status was significantly associated with executive dysfunction in PD.

Culture–gene coevolution of individualism–collectivism and the serotonin transporter gene

PubMed Central

Chiao, Joan Y.; Blizinsky, Katherine D.

2010-01-01

Culture–gene coevolutionary theory posits that cultural values have evolved, are adaptive and influence the social and physical environments under which genetic selection operates. Here, we examined the association between cultural values of individualism–collectivism and allelic frequency of the serotonin transporter functional polymorphism (5-HTTLPR) as well as the role this culture–gene association may play in explaining global variability in prevalence of pathogens and affective disorders. We found evidence that collectivistic cultures were significantly more likely to comprise individuals carrying the short (S) allele of the 5-HTTLPR across 29 nations. Results further show that historical pathogen prevalence predicts cultural variability in individualism–collectivism owing to genetic selection of the S allele. Additionally, cultural values and frequency of S allele carriers negatively predict global prevalence of anxiety and mood disorder. Finally, mediation analyses further indicate that increased frequency of S allele carriers predicted decreased anxiety and mood disorder prevalence owing to increased collectivistic cultural values. Taken together, our findings suggest culture–gene coevolution between allelic frequency of 5-HTTLPR and cultural values of individualism–collectivism and support the notion that cultural values buffer genetically susceptible populations from increased prevalence of affective disorders. Implications of the current findings for understanding culture–gene coevolution of human brain and behaviour as well as how this coevolutionary process may contribute to global variation in pathogen prevalence and epidemiology of affective disorders, such as anxiety and depression, are discussed. PMID:19864286

Molecular Epidemiological Survey of Glucose-6-Phosphate Dehydrogenase Deficiency and Thalassemia in Uygur and Kazak Ethnic Groups in Xinjiang, Northwest China.

PubMed

Han, Luhao; Su, Hai; Wu, Hao; Jiang, Weiying; Chen, Suqin

2016-06-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency and thalassemia occur frequently in tropical and subtropical regions, while the prevalence of relationship between the two diseases in Xinjiang has not been reported. We aimed to determine the prevalence of these diseases and clarify the relationship between genotypes and phenotypes of the two diseases in the Uygur and Kazak ethnic groups in Xinjiang. We measured G6PD activity by G6PD:6PGD (glucose acid-6-phosphate dehydrogenase) ratio, identified the gene variants of G6PD and α- and β-globin genes by polymerase chain reaction (PCR)-DNA sequencing and gap-PCR and compared these variants in different ethnic groups in Xinjiang with those adjacent to it. Of the 149 subjects with molecular analysis of G6PD deficiency conducted, a higher prevalence of the combined mutations c.1311C > T/IVSXI + 93T > C and IVSXI + 93T > C, both with normal enzymatic activities, were observed in the Uygur and Kazak subjects. A case of rare mutation HBB: c.135delC [codon 44 (-C) in the heterozygous state], a heterozygous case of HBB: c.68A > G [Hb G-Taipei or β22(B4)Glu→Gly] and several common single nucleotide polymorphisms (SNPs) were found on the β-globin gene. In conclusion, G6PD deficiency with pathogenic mutations and three common α-thalassemia (α-thal) [- -(SEA), -α(3.7) (rightward), -α(4.2) (leftward)] deletions and point mutations of the α-globin gene were not detected in the present study. The average incidence of β-thalassemia (β-thal) in Uygurs was 1.45% (2/138) in Xinjiang. The polymorphisms of G6PD and β-globin genes might be useful genetic markers to trace the origin and migration of the Uygur and Kazak in Xinjiang.

Association of vitamin D receptor gene polymorphisms with diabetic dyslipidemia in the elderly male population in North China.

PubMed

Xia, Zheng; Hu, Yazhuo; Han, Zhitao; Gao, Ya; Bai, Jie; He, Yao; Zhao, Hua; Zhang, Honghong

2017-01-01

The prevalence of dyslipidemia is rising alarmingly in elderly Han Chinese male patients with type 2 diabetes mellitus (T2DM). The genetic factors that contribute to the development of diabetic dyslipidemia remain incompletely identified. This study was conducted to assess the association between vitamin D receptor (VDR) polymorphisms and development of dyslipidemia in the Han elderly male population with T2DM in North China. A total of 242 T2DM patients with dyslipidemia (DH group, n=108) or without dyslipidemia (DO group, n=134) and 100 controls were genotyped for ApaI, TaqI and FokI single nucleotide polymorphisms (SNPs) of the VDR gene using polymerase chain reaction-restriction fragment length polymorphism and sequencing. The frequency and distribution of the SNPs were compared between cases and controls. The distribution of genotypes of VDR-FokI was significantly different between the control and DM group ( P =0.033), as well as between the control and DH subgroup ( P =0.011) but not DO subgroup ( P =0.111). The frequency of C allele and CC genotype of FokI was significantly higher in the DH patients than in the controls ( P =0.015 and P =0.003, respectively). Logistic regression analysis in a dominant model homozygous for the C allele of the FokI SNP showed that CC genotype was associated with DH patients (OR =1.797, 95% CI: 1.077-2.999, P =0.025). Significant associations of the ApaI and TaqI SNPs with either DO or DH subjects were not observed. These findings suggest that CC genotype of VDR-FokI is a risk factor for T2DM patients with dyslipidemia in elderly males in North China.

Role of CYP2E1 gene polymorphisms association with hepatitis risk in Northeast India

PubMed Central

Deka, Manab; Bose, Moumita; Baruah, Bharati; Bose, Purabi Deka; Medhi, Subhash; Bose, Sujoy; Saikia, Anjan; Kar, Premashish

2010-01-01

AIM: To investigate hepatitis virus, genetic and environmental factors, and their interactions in predisposing patients to liver diseases in Northeast India. METHODS: A total of 104 jaundice patients and 124 community controls were included. Serological analysis was performed by routine enzyme-linked immunosorbent assay, and nucleic acid testing for hepatitis viruses was done by polymerase chain reaction (PCR), followed by PCR direct sequencing for viral genotyping. Cytochrome P450 2E1 (CYP2E1) polymorphism was studied by PCR-restriction fragment length polymorphism. Nitrite and volatile nitrosamines in indigenous foods consumed routinely by the Northeast Indian ethnic population were estimated by Griess’s reagent and GC-MS, respectively. RESULTS: Hepatitis A virus (HAV) infection was predominantly prevalent (36.5%) in our cohort, followed by hepatitis B virus (HBV), hepatitis E virus (HEV) and hepatitis C virus. HBV genotype D and HEV genotype 1 were the most dominant. CYP2E1 c1/c2 genotype frequency was comparatively higher in alcoholic (P < 0.0001, OR = 30.5) and cryptogenic (P = 0.014, OR = 8.714) patients, and was associated with significantly higher hepatitis risk (P = 0.0.007, OR = 6.489). Mutant C allele of Cyp2E1 DraI frequency was comparatively higher in HAV (P = 0.006), alcoholic (P = 0.003) and cryptogenic (P = 0.014) cases, and was associated with overall hepatitis risk (P = 0.026, OR = 5.083). Indigenous foods, Gundruk, Kharoli, betel leaf and nuts were found to have the highest nitrite content. CONCLUSION: Apart from viral factors, CYP2E1 polymorphism might be associated with increased risk of liver diseases in Northeast India. Indigenous foods that contain nitrite and nitrosamine might be an associated risk factor. PMID:20939108

GPX1 Pro198Leu polymorphism and GSTM1 deletion do not affect selenium and mercury status in mildly exposed Amazonian women in an urban population.

PubMed

Rocha, Ariana V; Rita Cardoso, Bárbara; Zavarize, Bruna; Almondes, Kaluce; Bordon, Isabella; Hare, Dominic J; Teixeira Favaro, Déborah Inês; Franciscato Cozzolino, Silvia Maria

2016-11-15

Mercury is potent toxicant element, but its toxicity can be reduced by forming a complex with selenium for safe excretion. Considering the impact of mercury exposure in the Amazon region and the possible interaction between these two elements, we aimed to assess the effects of Pro198Leu polymorphism to GPX1 and GSTM1 deletion, on mercury levels in a population from Porto Velho, an urban locality in the Brazilian Amazon region. Two hundred women from the capital city of Rondônia state were recruited for this study with 149 deemed suitable to participate. We assessed dietary intake using 24-hour recall. Selenium levels in plasma and erythrocytes were measured using hydride generation quartz tube atomic absorption spectroscopy and total hair mercury using cold vapor atomic absorption spectrometry. Oxidative stress parameters (GPx activity, oxygen radical absorbency capacity [ORAC] and malondialdehyde [MDA]) were also analyzed. All participants were genotyped for Pro198Leu polymorphism and GSTM1 deletion. We observed that this population presented high prevalence of selenium deficiency, and also low levels of mercury, likely due to food habits that did not include selenium-rich food sources or significant consumption of fish (mercury biomagnifiers) regularly. Univariate statistical analysis showed that Pro198Leu and GSTM1 genotypes did not affect selenium and mercury levels in this population. Pro198Leu polymorphism and GSTM1 deletion had no effect on mercury levels in mildly exposed people, suggesting these genetic variants impact mercury levels only in highly exposed populations. Copyright © 2016 Elsevier B.V. All rights reserved.

Functional polymorphisms of the coagulation factor II gene (F2) and susceptibility to systemic lupus erythematosus (SLE)

PubMed Central

Demirci, F. Yesim K.; Dressen, Amy S.; Kammerer, Candace M.; Barmada, M. Michael; Kao, Amy H.; Ramsey-Goldman, Rosalind; Manzi, Susan; Kamboh, M. Ilyas

2011-01-01

Objective Two F2 functional polymorphisms, rs1799963 (G20210A) and rs3136516 (A19911G), are known to be associated with elevated prothrombin (encoded by F2) levels/activity and thrombosis risk. Since systemic lupus erythematosus (SLE) patients have high risk of thrombosis and accelerated atherosclerosis and also high prevalence of anti-prothrombin antibodies, we hypothesized that these two F2 polymorphisms could affect SLE risk. Methods We investigated these polymorphisms in 627 women with SLE (84% Caucasian Americans, 16% African Americans) and 657 female controls (78% Caucasian Americans, 22% African Americans). Results While the rs1799963 A allele was almost absent in African Americans, it was present at ~2% frequency in Caucasian Americans and showed no significant association with SLE. The rs3136516 G allele frequency was significantly higher in Caucasian SLE cases than controls (48.4% vs. 43.7%) with a covariate-adjusted odds ratio (OR) of 1.22 (95%CI: 1.03–1.46; P = 0.023). The association was replicated in African Americans (rs3136516 G allele frequency: 91.2% in cases vs. 82.2% in controls) with an adjusted OR of 1.96 (95%CI: 1.08–3.58; P = 0.022). Stratification of Caucasian SLE patients based on the presence or absence of cardiac and vascular events (CVE) revealed stronger association with the CVE-positive SLE subgroup than the CVE-negative SLE subgroup (OR: 1.42 vs. 1.20). Prothrombin activity measurements in a subset of SLE cases demonstrated higher activity in the carriers of the rs3136516 G allele. Conclusion Our results suggest a potential role for prothrombin and the crosstalk between hemostatic and immune/inflammatory systems in SLE and SLE-associated cardiovascular events, which warrant further investigation in independent samples. PMID:21239755

Functional polymorphisms of the coagulation factor II gene (F2) and susceptibility to systemic lupus erythematosus.

PubMed

Demirci, F Yesim K; Dressen, Amy S; Kammerer, Candace M; Barmada, M Michael; Kao, Amy H; Ramsey-Goldman, Rosalind; Manzi, Susan; Kamboh, M Ilyas

2011-04-01

Two F2 functional polymorphisms, rs1799963 (G20210A) and rs3136516 (A19911G), are known to be associated with elevated levels/activity of prothrombin (encoded by F2) and risk of thrombosis. Since patients with systemic lupus erythematosus (SLE) have high risk of thrombosis and accelerated atherosclerosis and also high prevalence of anti-prothrombin antibodies, we hypothesized that these two F2 polymorphisms could affect risk of SLE. We investigated these polymorphisms in 627 women with SLE (84% Caucasian Americans, 16% African Americans) and 657 female controls (78% Caucasian Americans, 22% African Americans). While the rs1799963 A allele was almost absent in African Americans, it was present at ~2% frequency in Caucasian Americans and showed no significant association with SLE. The rs3136516 G allele frequency was significantly higher in Caucasian SLE cases than in controls (48.4% vs 43.7%, respectively) with a covariate-adjusted odds ratio (OR) of 1.22 (95% CI 1.03-1.46, p = 0.023). The association was replicated in African Americans (rs3136516 G allele frequency 91.2% in cases vs 82.2% in controls) with an adjusted OR of 1.96 (95% CI 1.08-3.58, p = 0.022). Stratification of Caucasian SLE patients based on the presence or absence of cardiac and vascular events (CVE) revealed stronger association with the CVE-positive SLE subgroup than the CVE-negative SLE subgroup (OR 1.42 vs 1.20). Prothrombin activity measurements in a subset of SLE cases demonstrated higher activity in the carriers of the rs3136516 G allele. Our results suggest a potential role for prothrombin and the crosstalk between hemostatic and immune/inflammatory systems in SLE and SLE-associated cardiovascular events, which warrants further investigation in independent samples.

Interleukin-6 genotypes and serum levels in Chinese Hui population

PubMed Central

Gao, Shu-Ping; Liang, Shu; Pan, Min; Sun, Rong-Liang; Chen, Chu; Luan, Hong; Jiang, Min-Hui

2014-01-01

Interleukin-6 (IL-6) is a key pro-inflammatory cytokine involved in different physiologic and pathophysiologic processes, and circulating levels of IL-6 differ greatly between individuals. The Chinese Hui is one of the largest ethnic minorities, little is known about the distribution of IL-6 genetic variations and their effects on serum levels in Hui population. The aim of the present study is to determine the prevalence of -174G/C (rs1800795), -597G/A (rs1800797), and -634C/G (rs1800796) polymorphisms in the IL-6 gene promoter region and their association with IL-6 serum levels in the Ningxia Hui population. A total of 96 Hui subjects, (57 men and 39 women; mean age 49.65 ± 19.73 years) unrelated nationality residents in Ningxia Hui Autonomous Region were enrolled. Genotyping of the three polymorphisms were performed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) combined with gel electrophoresis and then confirmed by direct sequencing. The -174G/C (97.92% GG, 2.08% GC, and 0% CC) and -597G/A (98.96% GG, 1.04% GA, and 0% AA) polymorphisms were rare. The frequencies of -634C/G genotypes CC, CG, and GG were found to be 54.17%, 40.62%, and 5.21%, respectively in total studied subjects, the derived allele frequencies for the C and G alleles were 74.48% and 25.52%. Increased IL-6 levels were correlated with the IL-6 -634G allele carriers (CG+GG genotypes). The results suggest that IL-6 -174G/C and -597G/A are rare but -634C/G is common in the Ningxia Hui population, and the -634G allele is associated with circulating levels of IL-6. PMID:25356148

[Catalase gene rs1001179 polymorphism and oxidative stress in patients with chronic hepatitis C and ulcerative colitis].

PubMed

Bulatova, I A; Tretyakova, Yu I; Shchekotov, V V; Shchekotova, A P; Ulitina, P V; Krivtsov, A V; Nenasheva, O Yu

2015-01-01

To study the rs1001179 polymorphism of the catalase (CAT) gene and to estimate the serum levels of the enzymes catalase and glutathione peroxidase (GP) in patients with chronic hepatitis C (CHC) and in those with ulcerative colitis (UC) in the Perm Territory. Ninety patients with reactivation-phase CHC and 50 patients with exacerbation-phase UC were examined. The serum levels of catalase and GP were determined and the polymorphic variants of the marker of CAT gene rs1001179 in the DNA isolated from whole blood were found in all the patients. In the CHC and UC groups, the levels of catalase and GP were found to be lower than that in apparently healthy individuals. Furthermore, both groups showed a direct correlation between the activities of the enzymes. In the patients with CHC and in those with UC, the spread of genotypes and alleles generally failed to virtually differ from that in the control group. The G/G genotype was prevalent in all the groups. In the patients with CHC, the minor A allele demonstrated a significant inverse correlation with the enzyme catalase (r = -0.16; p = 0.02) and GP (r = -0.13; p = 0.047). The lower serum levels of catalase and GP are indicative of oxidative stress in the patients with CHC or UC. In the patients with CHC, the significant correlation of the pathological rs1701179 A allele marker with the processes of synthesis of antioxidant enzymes may suggest that CAT gene polymorphism in the A/A homozygotes might affect the regulation mechanism involved in the antioxidant system in the liver.

Genetic polymorphism in paraoxonase is a risk factor for childhood focal segmental glomerulosclerosis.

PubMed

Frishberg, Y; Toledano, H; Becker-Cohen, R; Feigin, E; Halle, D

2000-12-01

Focal segmental glomerulosclerosis (FSGS) is an important cause of end-stage renal failure (ESRF) in children. Our previous studies have shown that Arab children in Israel have a worse prognosis compared with Jewish patients despite similar clinical presentation and management. Progression of proteinuric glomerular diseases has been associated with alterations in lipid metabolism, and similarities have been drawn between the mechanisms underlying atherosclerosis and glomerulosclerosis. Paraoxonase (PON) is a high-density lipoprotein (HDL)-associated enzyme involved in preventing the oxidation of low-density lipoprotein (LDL), and an association has been shown between two genetic polymorphisms in PON1 and the risk of coronary artery disease. The aim of this study was to determine the frequency of these genetic polymorphisms in PON1 in Arab and Jewish children with FSGS and to determine any association with severity of outcome. Forty-seven children (21 Arab and 26 Jewish) with biopsy-proven FSGS and 274 healthy controls of matching ethnic origin were studied. The glutamine (A)-192-arginine (B) and the methionine (M)-55-leucine (L) polymorphisms were analyzed. The frequency of the A allele was similar in patients and controls (0.68 versus 0.71), as was that of the L allele (0.63 versus 0.6). When subgroups were analyzed, the prevalence of the LL genotype in Arab patients was significantly greater than in Jewish patients (57.1% versus 26.9%, P: < 0.05) and Arab controls (57.1% versus 28.9%, P: < 0.03). A trend in association was found between homozygosity for the L allele and progression of renal disease in Arab children. Homozygosity for the L allele is a risk factor for developing FSGS in Arab children and may be associated with a worse prognosis.

Polymorphisms in the interleukin 13 and GATA binding protein 3 genes and the development of eczema during childhood

PubMed Central

Arshad, S.H.; Karmaus, W.; Kurukulaaratchy, R.; Sadeghnejad, A.; Huebner, M.; Ewart, S.

2009-01-01

Summary Background Atopic eczema is characterized by Th2-dominant immunity with the cytokine interleukin 13 and the transcription factor GATA binding protein 3 playing a critical role. Objectives We assessed the association of polymorphisms in the IL13 and GATA3 genes with childhood eczema. Methods A birth cohort (n = 1456) was established on the Isle of Wight in 1989 and followed at the ages of 1 (n = 1167), 2 (n = 1174), 4 (n = 1218) and 10 years (n = 1373) to determine the prevalence of allergic disease including eczema. At 4 and 10 years, skin prick testing was performed. Whole blood samples (n = 923) were obtained at the 10-year assessment, stored frozen, and genotyped. Five polymorphisms from IL13 and seven from GATA3 were genotyped for this analysis. Repeated measurement analyses were conducted for the occurrence of eczema at ages 1, 2, 4 and 10 years. All analyses were adjusted for maternal and paternal eczema, low birth weight (< 2500 g), breastfeeding ≥ 3 months and age. Results IL13 was not associated with childhood eczema. For GATA3, the single nucleotide polymorphism (SNP) rs2275806 (promoter region) showed an increased odds ratio for atopic eczema independent of whether the comparison group had a positive skin prick test. The SNP rs444762 (intron 3 region) was associated with atopic eczema in comparison with children without eczema. The increased relative risks remained significant after adjustment for multiple testing only for rs2275806 (P < 0Æ05). Conclusions A SNP in GATA3 is associated with atopic eczema. This finding highlights the importance of GATA3 as an immune-modulating gene in atopic eczema. PMID:18410415

The Influence of OLR1 and PCSK9 Gene Polymorphisms on Ischemic Stroke: Evidence from a Meta-Analysis

PubMed Central

Au, Anthony; Griffiths, Lyn R.; Cheng, Kian-Kai; Wee Kooi, Cheah; Irene, Looi; Keat Wei, Loo

2015-01-01

Both OLR1 and PCSK9 genes are associated with atherosclerosis, cardiovascular disease and ischemic stroke. The overall prevalence of PCSK9 rs505151 and OLR1 rs11053646 variants in ischemic stroke were 0.005 and 0.116, respectively. However, to date, association between these polymorphisms and ischemic stroke remains inconclusive. Therefore, this first meta-analysis was carried out to clarify the presumed influence of these polymorphisms on ischemic stroke. All eligible case-control and cohort studies that met the search terms were retrieved in multiple databases. Demographic and genotyping data were extracted from each study, and the meta-analysis was performed using RevMan 5.3 and Metafor R 3.2.1. The pooled odd ratios (ORs) and 95% confidence intervals (CIs) were calculated using both fixed- and random-effect models. Seven case-control studies encompassing 1897 cases and 2119 controls were critically evaluated. Pooled results from the genetic models indicated that OLR1 rs11053646 dominant (OR = 1.33, 95%  CI:1.11–1.58) and co-dominant models (OR = 1.24, 95%  CI:1.02–1.51) were significantly associated with ischemic stroke. For the PCSK9 rs505151 polymorphism, the OR of co-dominant model (OR = 1.36, 95%  CI:1.01–1.58) was found to be higher among ischemic stroke patients. In conclusion, the current meta-analysis highlighted that variant allele of OLR1 rs11053646 G > C and PCSK9 rs505151 A > G may contribute to the susceptibility risk of ischemic stroke. PMID:26666837

Association of lipoprotein lipase D9N polymorphism with myocardial infarction in type 2 diabetes: the genetics, outcomes, and lipids in type 2 diabetes (GOLD) study.

PubMed

Izar, Maria C; Helfenstein, Tatiana; Ihara, Silvia S; Relvas, Waldir G; Santos, Andreza O; Fischer, Simone C; Pinto, Leonor E; Lopes, Ieda E; Pomaro, Daniel R; Fonseca, Marilia I; Bodanese, Luis C; Moriguchi, Emilio H; Saraiva, Jose F; Introcaso, Luiz; Souza, Agnaldo D; Scartezini, Marileia; Torres, Kerginaldo P; Zagury, Leao; Jardim, Paulo C; Costa, Eduardo A; Tacito, Lucia H; Forti, Adriana; Magalhaes, Maria E; Chacra, Antonio R; Bertolami, Marcelo C; Loures-Vale, Andreia A; Barros, Marco A; Xavier, Hermes T; Lyra, Ruy; Argamanijan, Dikran; Guimaraes, Armenio; Novazzi, Jose P; Kasinski, Nelson; Afiune, Abrahao; Martinez, Tania L; Santos, Raul D; Nicolau, Jose C; Cesar, Luiz A; Povoa, Rui M; Carvalho, Antonio C; Han, Sang W; Fonseca, Francisco A

2009-05-01

The association of polymorphisms affecting lipid metabolism with the risk of myocardial infarction (MI) in type 2 diabetes mellitus was investigated. The Genetics, Outcomes and Lipids in type 2 Diabetes (GOLD) Study is a prospective, multicenter study, conducted on 990 patients presenting diabetes and MI (n=386), or diabetes without previous manifestation of stroke, peripheral or coronary arterial disease (n=604), recruited from 27 institutions in Brazil. APO A1 (A/G -75 and C/T +83) and APO C3 (C/G 3'UTR) non-coding sequences, CETP (Taq 1B), LPL (D9N), APO E (epsilon2, epsilon3, epsilon4,), PON-1 (Q192R), and two LCAT variants Arg(147)-->Trp and Tyr(171)-->Stop were tested by PCR-RFLP. There was a higher prevalence of LPL DN genotype (19% vs.12%, p=0.03) and a higher frequency of the N allele (11% vs. 7%) among subjects with MI when compared to controls, with an odds ratio of MI for carriers of 9N allele of 2.46 (95% CI=1.79-3.39, p<0.0001). This association was present in men and women, in non-smokers and in hypertensive patients. A logistic regression model including gender, duration of diabetes, systolic blood pressure, HDL-C, left ventricle hypertrophy and D9N polymorphism showed that the latter still remained significantly associated with MI (OR=1.50, 95% CI=1.02-2.25, p=0.049). These findings suggest that D9N polymorphism can be a useful risk marker for myocardial infarction and that further potential candidate genes should be screened for exploratory analysis and for future therapeutic intervention in diabetes.

The role of genetics in chronic wasting disease of North American cervids

USGS Publications Warehouse

Robinson, Stacie J.; Samuel, Michael D.; O'Rourke, Katherine; Johnson, Chad J.

2012-01-01

Chronic wasting disease (CWD) is a major concern for the management of North American cervid populations. This fatal prion disease has led to declines in populations which have high CWD prevalence and areas with both high and low infection rates have experienced economic losses in wildlife recreation and fears of potential spill-over into livestock or humans. Research from human and veterinary medicine has established that the prion protein gene (Prnp) encodes the protein responsible for transmissible spongiform encephalopathies (TSEs). Polymorphisms in the Prnp gene can lead to different prion forms that moderate individual susceptibility to and progression of TSE infection. Prnp genes have been sequenced in a number of cervid species including those currently infected by CWD (elk, mule deer, white-tailed deer, moose) and those for which susceptibility is not yet determined (caribou, fallow deer, sika deer). Over thousands of sequences examined, the Prnp gene is remarkably conserved within the family Cervidae; only 16 amino acid polymorphisms have been reported within the 256 amino acid open reading frame in the third exon of the Prnp gene. Some of these polymorphisms have been associated with lower rates of CWD infection and slower progression of clinical CWD. Here we review the body of research on Prnp genetics of North American cervids. Specifically, we focus on known polymorphisms in the Prnp gene, observed genotypic differences in CWD infection rates and clinical progression, mechanisms for genetic TSE resistance related to both the cervid host and the prion agent and potential for natural selection for CWD-resistance. We also identify gaps in our knowledge that require future research.

Toxoplasma and reaction time: role of toxoplasmosis in the origin, preservation and geographical distribution of Rh blood group polymorphism.

PubMed

Novotná, M; Havlícek, J; Smith, A P; Kolbeková, P; Skallová, A; Klose, J; Gasová, Z; Písacka, M; Sechovská, M; Flegr, J

2008-09-01

The RhD protein which is the RHD gene product and a major component of the Rh blood group system carries the strongest blood group immunogen, the D-antigen. This antigen is absent in a significant minority of the human population (RhD-negatives) due to RHD deletion or alternation. The origin and persistence of this RhD polymorphism is an old evolutionary enigma. Before the advent of modern medicine, the carriers of the rarer allele (e.g. RhD-negative women in the population of RhD-positives or RhD-positive men in the population of RhD-negatives) were at a disadvantage as some of their children (RhD-positive children born to pre-immunized RhD-negative mothers) were at a higher risk of foetal or newborn death or health impairment from haemolytic disease. Therefore, the RhD-polymorphism should be unstable, unless the disadvantage of carriers of the locally less abundant allele is counterbalanced by, for example, higher viability of the heterozygotes. Here we demonstrated for the first time that among Toxoplasma-free subjects the RhD-negative men had faster reaction times than Rh-positive subjects and showed that heterozygous men with both the RhD plus and RhD minus alleles were protected against prolongation of reaction times caused by infection with the common protozoan parasite Toxoplasma gondii. Our results suggest that the balancing selection favouring heterozygotes could explain the origin and stability of the RhD polymorphism. Moreover, an unequal prevalence of toxoplasmosis in different countries could explain pronounced differences in frequencies of RhD-negative phenotype in geographically distinct populations.

Analysis of antibodies to newly described Plasmodium falciparum merozoite antigens supports MSPDBL2 as a predicted target of naturally acquired immunity.

PubMed

Tetteh, Kevin K A; Osier, Faith H A; Salanti, Ali; Kamuyu, Gathoni; Drought, Laura; Failly, Marilyne; Martin, Christophe; Marsh, Kevin; Conway, David J

2013-10-01

Prospective studies continue to identify malaria parasite genes with particular patterns of polymorphism which indicate they may be under immune selection, and the encoded proteins require investigation. Sixteen new recombinant protein reagents were designed to characterize three such polymorphic proteins expressed in Plasmodium falciparum schizonts and merozoites: MSPDBL1 (also termed MSP3.4) and MSPDBL2 (MSP3.8), which possess Duffy binding-like (DBL) domains, and SURFIN4.2, encoded by a member of the surface-associated interspersed (surf) multigene family. After testing the antigenicities of these reagents by murine immunization and parasite immunofluorescence, we analyzed naturally acquired antibody responses to the antigens in two cohorts in coastal Kenya in which the parasite was endemic (Chonyi [n = 497] and Ngerenya [n = 461]). As expected, the prevalence and levels of serum antibodies increased with age. We then investigated correlations with subsequent risk of clinical malaria among children <11 years of age during 6 months follow-up surveillance. Antibodies to the polymorphic central region of MSPDBL2 were associated with reduced risk of malaria in both cohorts, with statistical significance remaining for the 3D7 allelic type after adjustment for individuals' ages in years and antibody reactivity to whole-schizont extract (Chonyi, risk ratio, 0.51, and 95% confidence interval [CI], 0.28 to 0.93; Ngerenya, risk ratio, 0.38, and 95% CI, 0.18 to 0.82). For the MSPDBL1 Palo Alto allelic-type antigen, there was a protective association in one cohort (Ngerenya, risk ratio, 0.53, and 95% CI, 0.32 to 0.89), whereas the other antigens showed no protective associations after adjustment. These findings support the prediction that antibodies to the polymorphic region of MSPDBL2 contribute to protective immunity.

Thyroid hormone receptor alpha gene variants increase the risk of developing obesity and show gene-diet interactions.

PubMed

Fernández-Real, J M; Corella, D; Goumidi, L; Mercader, J M; Valdés, S; Rojo Martínez, G; Ortega, F; Martinez-Larrad, M-T; Gómez-Zumaquero, J M; Salas-Salvadó, J; Martinez González, M A; Covas, M I; Botas, P; Delgado, E; Cottel, D; Ferrieres, J; Amouyel, P; Ricart, W; Ros, E; Meirhaeghe, A; Serrano-Rios, M; Soriguer, F; Estruch, R

2013-11-01

Thyroid hormone receptor-beta resistance has been associated with metabolic traits. THRA gene sequencing of an obese woman (index case) who presented as empirical thyroid hormone receptor-α (THRA) resistance, disclosed a polymorphism (rs12939700) in a critical region involved in TRα alternative processing. THRA gene variants were evaluated in three independent europid populations (i) in two population cohorts at baseline (n=3417 and n=2265), 6 years later (n=2139) and (ii) in 4734 high cardiovascular risk subjects (HCVR, PREDIMED trial). The minor allele of the index case polymorphism (rs12939700), despite having a very low frequency (4%), was significantly associated with higher body mass index (BMI) (P=0.042) in HCVR subjects. A more frequent THRA polymorphism (rs1568400) was associated with higher BMI in subjects from the population (P=0.00008 and P=0.05) after adjusting for several confounders. Rs1568400 was also strongly associated with fasting triglycerides (P dominant=3.99 × 10(-5)). In the same sample, 6 years later, age and sex-adjusted risk of developing obesity was significantly increased in GG homozygotes (odds ratio 2.93 (95% confidence interval, 1.05-6.95)). In contrast, no association between rs1568400 and BMI was observed in HCVR subjects, in whom obesity was highly prevalent. This might be explained by the presence of an interaction (P <0.001) among the rs1568400 variant, BMI and saturated fat intake. Only when saturated fat intake was high (>24.5 g d(-1)), GG carriers showed a significantly higher BMI than A carriers after controlling for energy intake and physical activity. THRA gene polymorphisms are associated with obesity development. This is a novel observation linking the THRA locus to metabolic phenotypes.

Oxytocin receptor gene polymorphisms, attachment, and PTSD: Results from the National Health and Resilience in Veterans Study.

PubMed

Sippel, Lauren M; Han, Shizhong; Watkins, Laura E; Harpaz-Rotem, Ilan; Southwick, Steven M; Krystal, John H; Olff, Miranda; Sherva, Richard; Farrer, Lindsay A; Kranzler, Henry R; Gelernter, Joel; Pietrzak, Robert H

2017-11-01

The human oxytocin system is implicated in social behavior and stress recovery. Polymorphisms in the oxytocin receptor gene (OXTR) may interact with attachment style to predict stress-related psychopathology like posttraumatic stress disorder (PTSD). The objective of this study was to examine independent and interactive effects of the OXTR single nucleotide polymorphism (SNP) rs53576, which has been associated with stress reactivity, support-seeking, and PTSD in prior studies, and attachment style on risk for PTSD in a nationally representative sample of 2163 European-American (EA) U.S. military veterans who participated in two independent waves of the National Health and Resilience in Veterans Study (NHRVS). Results revealed that insecure attachment style [adjusted odds ratio (OR) = 4.29; p < 0.001] and the interaction of rs53576 and attachment style (OR = 2.58, p = 0.02) were associated with probable lifetime PTSD. Among individuals with the minor A allele, the prevalence of probable PTSD was significantly higher among those with an insecure attachment style (23.9%) than those with a secure attachment style (2.0%), equivalent to an adjusted OR of 10.7. We attempted to replicate these findings by utilizing dense marker data from a genome-wide association study of 2215 high-risk civilians; one OXTR variant, though not rs53576, was associated with PTSD. Exploratory analyses in the veteran sample revealed that the interaction between this variant and attachment style predicting probable PTSD approached statistical significance. Results indicate that polymorphisms in the OXTR gene and attachment style may contribute to vulnerability to PTSD in U.S. military veterans. Published by Elsevier Ltd.

Calpain-10 gene polymorphisms and risk of type 2 diabetes mellitus in Mexican mestizos.

PubMed

Picos-Cárdenas, V J; Sáinz-González, E; Miliar-García, A; Romero-Zazueta, A; Quintero-Osuna, R; Leal-Ugarte, E; Peralta-Leal, V; Meza-Espinoza, J P

2015-03-27

The calpain-10 gene is expressed primarily in tissues important in glucose metabolism; thus, some of its polymorphisms have been associated with type 2 diabetes. In this study, we examined the association between the calpain-10 single-nucleotide polymorphism (SNP)-43, SNP-19, and SNP-63 and type 2 diabetes in Mexican mestizos. We included 211 patients and 152 non-diabetic subjects. Polymerase chain reaction was used to identify alleles. We compared allele, genotype, haplotype, and diplotype frequencies between both groups and used the chi-square test to calculate the risk. The allele frequency of SNP-43 allele 1 was 70% in controls and 72% in patients; the GG, GA, and AA genotype frequencies were 48.7, 42.8, and 8.5% in controls and 51.2, 41.7, and 7.1% in patients, respectively. For SNP- 19, the prevalence of allele 1 (2R) was 32% in controls and 39% in patients. In controls, homozygosity (2R/2R) was 10.5%, heterozygosity was 42.8%, and 3R/3R was 46.7%; in cases, these values were 13.3, 50.7, and 36.0%, respectively. For SNP-63, the frequency of allele 1 was 87% in controls and 83% in patients; genotype frequencies in controls were 75.7% (CC), 23% (CT), and 1.3% (TT), and were 69.7, 27.5, and 2.8%, respectively for the cases. Genotype distributions were consistent with Hardy-Weinberg equilibrium. No significant intergroup differences for allele, genotype, haplotype, or diplotype frequencies were observed. We found no association between these polymorphisms and diabetes. However, our sample size was small, so the role of calpain-10 risk alleles should be further examined.

Association of interleukin-6 gene polymorphisms with hand osteoarthritis and hand osteoporosis.

PubMed

Blumenfeld, Orit; Williams, Frances M K; Valdes, Ana; Hart, Deborah J; Malkin, Ida; Spector, Timothy D; Livshits, Gregory

2014-09-01

Several genes, including IL-6 encoding pro-inflammatory cytokines, are involved in development of osteoarthritis and osteoporosis. The association of radiographic hand osteoarthritis (RHOA) and osteoporosis related phenotypes (RHOP) with polymorphisms in IL-6 has been reported inconsistently. The aim of this study was to examine the association, between RHOA and RHOP and IL-6 polymorphisms in two independent samples. Two samples: UK females, including 1440 individuals assessed for RHOA and 3470 assessed for RHOP; Chuvash pedigree including 1499 females and males were assessed for RHOP and RHOA. SNPs were genotyped in the IL-6 genomic region, and used in association analysis with RHOA and RHOP phenotypes. RHOP phenotypes showed similar heritability estimates in both samples, ranging from 34.5 ± 5.5% to 61.0 ± 2.4%. RHOA in Chuvash had substantially lower heritability estimates compared to twins (e.g. OSP scores: 11.8 ± 2.3% vs. 39.2 ± 4.1%) with much higher prevalence and considerably stronger correlation with age (r = 0.811 vs. r = 0.505). RHOA in Chuvash sample may be traumatic in nature, caused by heavy and prolonged manual work related to their private farming. There were a number of statistically significant association results with both types of phenotypes. The most consistent result was obtained for JSN in both samples with SNP from the same haploblock. Their combined probability of no association was only p = 0.000003. Additionally, there were SNPs common for both RHOA and RHOP. We have shown polymorphisms in IL_6 are significantly associated with RHOA and hand RHOP in two samples having different ethnicity and lifestyle. Age × environment × genes interaction appears as an important factor of RHOA manifestation and progression. Copyright © 2014 Elsevier Ltd. All rights reserved.

Relationship between Occupational Stress, 5-HT2A Receptor Polymorphisms and Mental Health in Petroleum Workers in the Xinjiang Arid Desert: A Cross-Sectional Study.

PubMed

Jiang, Ting; Ge, Hua; Sun, Jian; Li, Rong; Han, Rui; Liu, Jiwen

2017-04-10

At present, there is growing interest in research examining the relationship between occupational stress and mental health. Owing to the socioeconomic impact of occupational stress and the unique environment of petroleum workers in Xinjiang, a cross-sectional study was carried out between April and December 2015 to investigate the relationship between occupational stress, 5-hydroxytryptamine receptor (5-HTR2A) genotype, and mental health. A total of 1485 workers were selected. The Symptom Checklist 90 was used to assess nine classes of psychological symptoms. Work-related stressors were evaluated using the Occupational Stress Inventory-Revised Edition. Levels of 5-HTR2A (the Tl02C and A-1438G single nucleotide polymorphism in the 5-HTR2A gene) were measured by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The findings of the present study revealed a high prevalence rate of mental health problems (40.29%) in petroleum workers stationed in the arid desert, and suggested a strong correlation between occupational stress and mental health. The TC and CC genotype of Tl02C were found to be protective factors against mental health problems (odds ratio (OR) = 0.455, 95% confidence interval (CI): = 0.269-0.771, odds ratio (OR) = 0.340, 95% confidence interval (CI): 0.162-0.716). AG and GG genotype of A-1438G [odds ratio (OR) 1 = 2.729, 95% confidence interval (CI): 1.433-5.195; odds ratio (OR) 2 = 2.480, 95% confidence interval (CI): 1.221-5.037] were revealed as risk factors. These data provide evidence that occupational stress and 5-HTR2A gene polymorphism contributes to the incidence of mental health problems.

The Q223R polymorphism in the leptin receptor associates with objectively measured light physical activity in free-living Japanese.

PubMed

Murakami, Haruka; Iemitsu, Motoyuki; Fuku, Noriyuki; Sanada, Kiyoshi; Gando, Yuko; Kawakami, Ryoko; Miyachi, Motohiko

2014-04-22

Physical activity (PA) is associated with reductions in the risk of all-cause mortality and in the prevalence of cardiovascular disease and stroke. Nevertheless, a large proportion of the general population may not be sufficiently active. PA level has been reported to be influenced by genetic factors, and we investigated whether Q223R polymorphism in the leptin receptor (LEPR) gene was associated with PA level. A total of 556 Japanese adults aged 24-65years old participated in this cross-sectional study. The duration and intensity of PA were objectively evaluated by triaxial accelerometry. Q223R polymorphism was determined by the TaqMan method. The distribution of Q223R polymorphism was: QQ 0.7%, QR 22.6%, and RR 76.6%. The relation between the LEPR genotype and PA level was analyzed by ANCOVA with age and sex as covariates in the Q dominant genetic model. There were significant differences between LEPR genotypes and the time spent in light PA or inactive time. The subjects with RR genotype showed significantly shorter time spent in light PA (RR genotype: 559.4±102.9min/day, QQ/QR genotype: 579.9±103.1min/day) and longer inactive time (RR genotype: 815.5±107.5min/day, QQ/QR genotype: 792.3±107.7min/day) than the subjects with QQ/QR genotype (P<0.05). There were no such differences in the time spent in moderate or vigorous PA. These results suggest that the variety of PA level, especially spontaneous PA in humans, is partly caused by diversity in the LEPR gene. Copyright © 2014. Published by Elsevier Inc.

Helicobacter Pylori Serology in Relation to Hepatitis C Virus Infection and IL28B Single Nucleotide Polymorphism

PubMed Central

Gutwerk, Alexander; Wex, Thomas; Stein, Kerstin; Langner, Cosima; Canbay, Ali; Malfertheiner, Peter

2018-01-01

The aim of the study was to evaluate the serological rate of Helicobacter pylori (H. pylori) infection in patients with chronic hepatitis C virus (HCV) infection and determine any correlations with liver damage and IL28B single-nucleotide polymorphism (SNP). One hundred eighty-nine patients with chronic HCV infection were included in the study, and H. pylori status was defined based on anti-H. pylori-IgG or anti-CagA-IgG antibodies using enzyme-linked immunosorbent assay (ELISA). Liver damage was assessed using histology or transient elastography. IL28B C/T polymorphism (rs12979860) was evaluated in circulating blood cells using a PCR-based restriction fragment length polymorphism assay. Overall H. pylori serology was positive in 38.1% of our HCV-infected subjects. Among those, the anti-CagA-IgG positivity rate was 43.1% and was within the range of previously described populations of the same region. Highest prevalence of H. pylori was found in patients between 31 and 40 years compared to other age subgroups. The seropositivity rate was higher in the non-cirrhotic group than the cirrhotic one (45.4% vs. 20.0%, p < 0.05). No difference was found in IL28B genotype between H. pylori-positive and -negative cohorts. However, we observed a trend for the lower anti-CagA-IgG expression level in relation to the IL28B T-allele. Our results do not support an association between HCV and H. pylori infection. Whether IL28B SNP has a functional role in modulation of serological response to H. pylori CagA needs further investigation. PMID:29510558

Investigation of inversion polymorphisms in the human genome using principal components analysis.

PubMed

Ma, Jianzhong; Amos, Christopher I

2012-01-01

Despite the significant advances made over the last few years in mapping inversions with the advent of paired-end sequencing approaches, our understanding of the prevalence and spectrum of inversions in the human genome has lagged behind other types of structural variants, mainly due to the lack of a cost-efficient method applicable to large-scale samples. We propose a novel method based on principal components analysis (PCA) to characterize inversion polymorphisms using high-density SNP genotype data. Our method applies to non-recurrent inversions for which recombination between the inverted and non-inverted segments in inversion heterozygotes is suppressed due to the loss of unbalanced gametes. Inside such an inversion region, an effect similar to population substructure is thus created: two distinct "populations" of inversion homozygotes of different orientations and their 1:1 admixture, namely the inversion heterozygotes. This kind of substructure can be readily detected by performing PCA locally in the inversion regions. Using simulations, we demonstrated that the proposed method can be used to detect and genotype inversion polymorphisms using unphased genotype data. We applied our method to the phase III HapMap data and inferred the inversion genotypes of known inversion polymorphisms at 8p23.1 and 17q21.31. These inversion genotypes were validated by comparing with literature results and by checking Mendelian consistency using the family data whenever available. Based on the PCA-approach, we also performed a preliminary genome-wide scan for inversions using the HapMap data, which resulted in 2040 candidate inversions, 169 of which overlapped with previously reported inversions. Our method can be readily applied to the abundant SNP data, and is expected to play an important role in developing human genome maps of inversions and exploring associations between inversions and susceptibility of diseases.

Molecular characterization of multidrug-resistant Mycobacterium tuberculosis isolates from high prevalence tuberculosis states in Mexico.

PubMed

Juarez-Eusebio, Dulce Maria; Munro-Rojas, Daniela; Muñiz-Salazar, Raquel; Laniado-Laborín, Rafael; Martinez-Guarneros, Jose Armando; Flores-López, Carlos A; Zenteno-Cuevas, Roberto

2017-11-01

Mexico is one of the most important contributors of multidrug resistance tuberculosis (MDR-TB) in Latin-America, however little is known about the molecular characteristics of these strains. For this reason, the objective of this work was to determine the genotype and characterize polymorphisms in genes associated with resistance to rifampicin, isoniazid, and second-line drugs in isolates from two regions of Mexico with high prevalence of drug resistant tuberculosis. Clinical isolates from individuals with confirmed MDR-TB were genotyped using MIRU-VNTR 12 loci. To characterize the polymorphisms in genes associated with resistance to rifampicin, isoniazid and second-line drugs; rpoB, katG, inhA, rrs, eis, gyrA, gyrB and tlyA were sequenced. 22 (41%) of the 54 MDR-TB isolates recovered were from the state of Baja California, while 32 (59%) were from Veracruz. The results show the katGS315T mutation was observed in 20% (11/54) of the isolates, while rpoBS315L was present in 33% (18/54). rrs had three polymorphisms (T1239C, ntA1401C and ntA1401G), gyrB presented no modifications, whereas gyrA showed five (S95T, F60Y, A90V, S91P and P124A), eis two (G-10A and A431G) and tlyA one (insertion at codon 67). Only 20% (11/54) of isolates were confirmed as MDR-TB by sequencing, and no mutations at any of the genes sequenced were observed in 43% (23/54) of the strains. Two isolates were recognized with the proper set of mutations like pre-XDR and one was XDR-TB. Eighteen isolates were classified as orphans and the remaining thirty-six were distributed in fourteen lineages, the most frequent were S (11%), Haarlem (9%), Ghana (9%) and LAM (7%). Out of the fourteen clusters identified, seven included unknown genotypes and nine had lineages. This is one of the most detailed analyses of genotypic characteristics and mutations associated with drug resistance to first and second-line drugs in MDR-TB isolates from Mexico. An important genetic variability and significant discrepancy between phenotypic tests and polymorphisms was observed. Our results set the need to screen additional loci as well as implement a molecular epidemiological surveillance system of MDR-TB in the country. Copyright © 2016 Elsevier B.V. All rights reserved.

GAD65 Promoter Polymorphism rs2236418 Modulates Harm Avoidance in Women via Inhibition/Excitation Balance in the Rostral ACC.

PubMed

Colic, Lejla; Li, Meng; Demenescu, Liliana Ramona; Li, Shija; Müller, Iris; Richter, Anni; Behnisch, Gusalija; Seidenbecher, Constanze I; Speck, Oliver; Schott, Björn H; Stork, Oliver; Walter, Martin

2018-05-30

Anxiety disorders are common and debilitating conditions with higher prevalence in women. However, factors that predispose women to anxiety phenotypes are not clarified. Here we investigated potential contribution of the single nucleotide polymorphism rs2236418 in GAD2 gene to changes in regional inhibition/excitation balance, anxiety-like traits, and related neural activity in both sexes. One hundred and five healthy individuals were examined with high-field (7T) multimodal magnetic resonance imaging (MRI); including resting-state functional MRI in combination with assessment of GABA and glutamate (Glu) levels via MR spectroscopy. Regional GABA/Glu levels in anterior cingulate cortex (ACC) subregions were assessed as mediators of gene-personality interaction for the trait harm avoidance and moderation by sex was tested. In AA homozygotes, with putatively lower GAD2 promoter activity, we observed increased intrinsic neuronal activity and higher inhibition/excitation balance in pregenual ACC (pgACC) compared with G carriers. The pgACC drove a significant interaction of genotype, region, and sex, where inhibition/excitation balance was significantly reduced only in female AA carriers. This finding was specific for rs2236418 as other investigated single nucleotide polymorphisms of the GABA synthesis related enzymes ( GAD1 , GAD2 , and GLS ) were not significant. Furthermore, only in women there was a negative association of pgACC GABA/Glu ratios with harm avoidance. A moderated-mediation model revealed that pgACC GABA/Glu also mediated the association between the genotype variant and level of harm avoidance, dependent on sex. Our data thus provide new insights into the neurochemical mechanisms that control emotional endophenotypes in humans and constitute predisposing factors for the development of anxiety disorders in women. SIGNIFICANCE STATEMENT Anxiety disorders are among the most common and burdensome psychiatric disorders, with higher prevalence rates in women. The causal mechanisms are, however, poorly understood. In this study we propose a neurobiological basis that could help to explain female bias of anxiety endophenotypes. Using magnetic resonance brain imaging and personality questionnaires we show an interaction of the genetic variation rs2236418 in the GAD2 gene and sex on GABA/glutamate (Glu) balance in the pregenual anterior cingulate cortex (pgACC), a region previously connected to affect regulation and anxiety disorders. The GAD2 gene polymorphism further influenced baseline neuronal activity in the pgACC. Importantly, GABA/Glu was shown to mediate the relationship between the genetic variant and harm avoidance, however, only in women. Copyright © 2018 the authors 0270-6474/18/385068-11$15.00/0.

Quantitative Analysis of Single-Nucleotide Polymorphism for Rapid Detection of TR34/L98H- and TR46/Y121F/T289A-Positive Aspergillus fumigatus Isolates Obtained from Patients in Iran from 2010 to 2014

PubMed Central

Mohammadi, Faezeh; Hashemi, Seyed Jamal; Zoll, Jan; Melchers, Willem J. G.; Rafati, Haleh; Dehghan, Parvin; Rezaie, Sasan; Tolooe, Ali; Tamadon, Yalda; van der Lee, Henrich A.; Verweij, Paul E.

2015-01-01

We employed an endpoint genotyping method to update the prevalence rate of positivity for the TR34/L98H mutation (a 34-bp tandem repeat mutation in the promoter region of the cyp51A gene in combination with a substitution at codon L98) and the TR46/Y121F/T289A mutation (a 46-bp tandem repeat mutation in the promoter region of the cyp51A gene in combination with substitutions at codons Y121 and T289) among clinical Aspergillus fumigatus isolates obtained from different regions of Iran over a recent 5-year period (2010 to 2014). The antifungal activities of itraconazole, voriconazole, and posaconazole against 172 clinical A. fumigatus isolates were investigated using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) broth microdilution method. For the isolates with an azole resistance phenotype, the cyp51A gene and its promoter were amplified and sequenced. In addition, using a LightCycler 480 real-time PCR system, a novel endpoint genotyping analysis method targeting single-nucleotide polymorphisms was evaluated to detect the L98H and Y121F mutations in the cyp51A gene of all isolates. Of the 172 A. fumigatus isolates tested, the MIC values of itraconazole (≥16 mg/liter) and voriconazole (>4 mg/liter) were high for 6 (3.5%). Quantitative analysis of single-nucleotide polymorphisms showed the TR34/L98H mutation in the cyp51A genes of six isolates. No isolates harboring the TR46/Y121F/T289A mutation were detected. DNA sequencing of the cyp51A gene confirmed the results of the novel endpoint genotyping method. By microsatellite typing, all of the azole-resistant isolates had genotypes different from those previously recovered from Iran and from the Dutch TR34/L98H controls. In conclusion, there was not a significant increase in the prevalence of azole-resistant A. fumigatus isolates harboring the TR34/L98H resistance mechanism among isolates recovered over a recent 5-year period (2010 to 2014) in Iran. A quantitative assay detecting a single-nucleotide polymorphism in the cyp51A gene of A. fumigatus is a reliable tool for the rapid screening and monitoring of TR34/L98H- and TR46/Y121F/T289A-positive isolates and can easily be incorporated into clinical mycology algorithms. PMID:26525787

Distribution of Chlamydia trachomatis serotypes in clinical urogenital samples from north-eastern Croatia.

PubMed

Bošnjak, Zinka; Džijan, Snježana; Pavlinić, Dinko; Perić, Magdalena; Ružman, Nataša; Križan, Ivana Roksandić; Lauc, Gordan; Antolović-Požgain, Arlen; Burazin, Jelena; Vuković, Dubravka

2012-06-01

The purpose of this study was to determine prevalence of Chlamydia trachomatis (Ct) urogenital infection and its serotype distribution from clinical samples in north-eastern Croatia. During a 3-year period, 2,379 urogenital samples were analyzed by real-time polymerase chain reaction (A group), while 4,846 genital swabs were analyzed by direct fluorescent antibody test (B group). 132 Ct positive specimens were genotyped by omp1 gene sequencing. The prevalence rate of Ct was 3.2 % in A and 1 % in B group. The most prevalent chlamydial genotype was E (44 %), followed by F (33 %), K (11.5 %), G (8 %), J/UW (5.3 %), D-IC (4.4 %), D-B120 (1.8 %), and B/IU, J/IU, Ia/IU (0.9 % each) serotypes. Single-nucleotide polymorphisms (SNPs) of omp1 gene were detected in E, K, and G serotypes. Some of these SNPs (C/T at position 272 and G/A at position 813 in E strain; C/T at position 884 in D strain) might represent novel omp1 variants.

Cardiometabolic risk in polycystic ovary syndrome.

PubMed

Bajuk Studen, Katica; Pfeifer, Marija

2018-05-29

Polycystic ovary syndrome (PCOS) is a common disorder in women of reproductive age. Besides hyperandrogenism, oligomenorrhea and fertility issues, it is associated with a high prevalence of metabolic disorders and cardiovascular risk factors. Several genetic polymorphisms have been identified for possible associations with cardiometabolic derangements in PCOS. Different PCOS phenotypes differ significantly in their cardiometabolic risk which is worsening with severity of androgen excess. Due to methodological difficulties longer time-scale data about cardiovascular morbidity and mortality in PCOS and about possible beneficial effects of different treatment interventions is missing leaving many issues regarding cardiovascular risk unresolved.

The genetics of exceptional longevity: Insights from centenarians.

PubMed

Santos-Lozano, Alejandro; Santamarina, Ana; Pareja-Galeano, Helios; Sanchis-Gomar, Fabian; Fiuza-Luces, Carmen; Cristi-Montero, Carlos; Bernal-Pino, Aranzazu; Lucia, Alejandro; Garatachea, Nuria

2016-08-01

As the world population ages, so the prevalence increases of individuals aged 100 years or more, known as centenarians. Reaching this age has been described as exceptional longevity (EL) and is attributed to both genetic and environmental factors. Many genetic variations known to affect life expectancy exist in centenarians. This review of studies conducted on centenarians and supercentenarians (older than 110 years) updates knowledge of the impacts on longevity of the twenty most widely investigated single nucleotide polymorphisms (SNPs). Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Seasonal Affective Disorder

PubMed Central

Rohan, Kelly J.

2005-01-01

Seasonal affective disorder (SAD), characterized by fall/winter major depression with spring/summer remission, is a prevalent mental health problem. SAD etiology is not certain, but available models focus on neurotransmitters, hormones, circadian rhythm dysregulation, genetic polymorphisms, and psychological factors. Light therapy is established as the best available treatment for SAD. Alternative and/or supplementary approaches involving medications, cognitive-behavioral therapy, and exercise are currently being developed and evaluated. Given the complexity of the disorder, interdisciplinary research stands to make a significant contribution to advancing our understanding of SAD conceptualization and treatment. PMID:21179639

Genetic variations in GPSM3 associated with protection from rheumatoid arthritis affect its transcript abundance

PubMed Central

Gall, BJ; Wilson, A; Schroer, AB; Gross, JD; Stoilov, P; Setola, V; Watkins, CM; Siderovski, DP

2015-01-01

G protein signaling modulator 3 (GPSM3) is a regulator of G protein-coupled receptor signaling, with expression restricted to leukocytes and lymphoid organs. Previous genome-wide association studies have highlighted single-nucleotide polymorphisms (SNPs rs204989, rs204991) in a region upstream of the GPSM3 transcription start site as being inversely correlated to the prevalence of rheumatoid arthritis (RA) -- this association is supported by the protection afforded to Gpsm3-deficient mice in models of inflammatory arthritis. Here, we assessed the functional consequences of these polymorphisms. We collected biospecimens from 50 volunteers with RA diagnoses, 50 RA-free volunteers matched to the aforementioned group, and 100 unmatched healthy young volunteers. We genotyped these individuals for GPSM3 (rs204989, rs204991), CCL21 (rs2812378), and HLA gene region (rs6457620) polymorphisms, and found no significant differences in minor allele frequencies between the RA and disease-free cohorts. However, we identified that individuals homozygous for SNPs rs204989 and rs204991 had decreased GPSM3 transcript abundance relative to individuals homozygous for the major allele. In vitro promoter activity studies suggest that SNP rs204989 is the primary cause of this decrease in transcript levels. Knockdown of GPSM3 in THP-1 cells, a human monocytic cell line, was found to disrupt ex vivo migration to the chemokine MCP-1. PMID:26821282

Interaction between VEGF receptor-2 gene polymorphisms and dietary patterns on blood glucose and lipid levels in Chinese Malaysian adults.

PubMed

Yap, Roseline Wai Kuan; Shidoji, Yoshihiro; Hon, Wei Min; Masaki, Motofumi

2011-01-01

The prevalence of lifestyle-related chronic diseases is increasing and gene-diet interaction studies are limited among the Malaysian population. This study was conducted to evaluate the association and interaction effects of vascular endothelial growth factor receptor-2(VEGFR2) gene polymorphisms and dietary patterns on anthropometric and biochemical risk factors of chronic diseases in 179 Chinese Malaysian adults. Genotyping of rs1870377 and rs2071559 was performed by real-time PCR using TaqMan probes. Dietary patterns were constructed from the food frequency questionnaire using factor analysis. Anthropometric measurements: body mass index (BMI), systolic and diastolic blood pressure and biomarkers: blood glucose, glycated hemoglobin A1c (HbA1c) and lipids were obtained. Two dietary patterns: 'Balanced diet' and 'Meat, rice and noodles diet' (MRND) were extracted. MRND was associated with higher BMI, blood pressure, blood glucose and lipids, while T alleles in both rs1870377 and rs2071559 were associated with higher blood lipids (p < 0.05). The interaction of MRND and rs1870377 had a borderline effect on blood HbA1c after adjusting for confounders (p = 0.057). A dietary pattern of MRND and VEGFR2 gene polymorphisms were both associated with increased health risks of lifestyle-related chronic diseases particularly blood glucose and lipid levels in Chinese Malaysian adults. Copyright © 2012 S. Karger AG, Basel.

Rate of resistance evolution and polymorphism in long- and short-lived hosts.

PubMed

Bruns, Emily; Hood, Michael E; Antonovics, Janis

2015-02-01

Recent theoretical work has shown that long-lived hosts are expected to evolve higher equilibrium levels of disease resistance than shorter-lived hosts, but questions of how longevity affects the rate of resistance evolution and the maintenance of polymorphism remain unanswered. Conventional wisdom suggests that adaptive evolution should occur more slowly in long-lived organisms than in short-lived organisms. However, the opposite may be true for the evolution of disease-resistance traits where exposure to disease, and therefore the strength of selection for resistance increases with longevity. In a single locus model of innate resistance to a frequency-dependent, sterilizing disease, longer lived hosts evolved resistance more rapidly than short-lived hosts. Moreover, resistance in long-lived hosts could only be polymorphic for more costly and more extreme resistance levels than short-lived hosts. The increased rate of evolution occurred in spite of longer generation times because longer-lived hosts had both a longer period of exposure to disease as well as higher disease prevalence. Qualitatively similar results were found when the model was extended to mortality-inducing diseases, or to density-dependent transmission modes. Our study shows that the evolutionary dynamics of host resistance is determined by more than just levels of resistance and cost, but is highly sensitive to the life-history traits of the host. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.