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Sample records for a18 gene polymorphism

  1. Inflammatory Gene Polymorphisms in Lung Cancer Susceptibility.

    PubMed

    Eaton, Keith D; Romine, Perrin E; Goodman, Gary E; Thornquist, Mark D; Barnett, Matt J; Petersdorf, Effie W

    2018-05-01

    Chronic inflammation has been implicated in carcinogenesis, with increasing evidence of its role in lung cancer. We aimed to evaluate the role of genetic polymorphisms in inflammation-related genes in the risk for development of lung cancer. A nested case-control study design was used, and 625 cases and 625 well-matched controls were selected from participants in the β-Carotene and Retinol Efficacy Trial, which is a large, prospective lung cancer chemoprevention trial. The association between lung cancer incidence and survival and 23 polymorphisms descriptive of 11 inflammation-related genes (interferon gamma gene [IFNG], interleukin 10 gene [IL10], interleukin 1 alpha gene [IL1A], interleukin 1 beta gene [IL1B], interleukin 2 gene [IL2], interleukin 4 receptor gene [IL4R], interleukin 4 gene [IL4], interleukin 6 gene [IL6], prostaglandin-endoperoxide synthase 2 gene [PTGS2] (also known as COX2), transforming growth factor beta 1 gene [TGFB1], and tumor necrosis factor alpha gene [TNFA]) was evaluated. Of the 23 polymorphisms, two were associated with risk for lung cancer. Compared with individuals with the wild-type (CC) variant, individuals carrying the minor allele variants of the IL-1β-511C>T promoter polymorphism (rs16944) (CT and TT) had decreased odds of lung cancer (OR = 0.74, [95% confidence interval (CI): 0.58-0.94] and OR = 0.71 [95% CI: 0.50-1.01], respectively, p = 0.03). Similar results were observed for the IL-1β-1464 C>G promoter polymorphism (rs1143623), with presence of the minor variants CG and CC having decreased odds of lung cancer (OR = 0.75 [95% CI: 0.59-0.95] and OR = 0.69 [95% CI: 0.46-1.03], respectively, p = 0.03). Survival was not influenced by genotype. This study provides further evidence that IL1B promoter polymorphisms may modulate the risk for development of lung cancer. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  2. 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

  3. Gene polymorphisms associated with functional dyspepsia.

    PubMed

    Kourikou, Anastasia; Karamanolis, George P; Dimitriadis, George D; Triantafyllou, Konstantinos

    2015-07-07

    Functional dyspepsia (FD) is a constellation of functional upper abdominal complaints with poorly elucidated pathophysiology. However, there is increasing evidence that susceptibility to FD is influenced by hereditary factors. Genetic association studies in FD have examined genotypes related to gastrointestinal motility or sensation, as well as those related to inflammation or immune response. G-protein b3 subunit gene polymorphisms were first reported as being associated with FD. Thereafter, several gene polymorphisms including serotonin transporter promoter, interlukin-17F, migration inhibitory factor, cholecystocynine-1 intron 1, cyclooxygenase-1, catechol-o-methyltransferase, transient receptor potential vanilloid 1 receptor, regulated upon activation normal T cell expressed and secreted, p22PHOX, Toll like receptor 2, SCN10A, CD14 and adrenoreceptors have been investigated in relation to FD; however, the results are contradictory. Several limitations underscore the value of current studies. Among others, inconsistencies in the definitions of FD and controls, subject composition differences regarding FD subtypes, inadequate samples, geographical and ethnical differences, as well as unadjusted environmental factors. Further well-designed studies are necessary to determine how targeted genes polymorphisms, influence the clinical manifestations and potentially the therapeutic response in FD.

  4. [Gene polymorphisms in patients with Down's syndrome].

    PubMed

    Kuz'mina, N S; Ushenkova, L I; Shagirova, Zh M; Sheĭkhaev, G O; Mikhaĭlov, V F; Kurbatova, L A; Mazurik, V K; Rubanovich, A V; Zasukhina, G D

    2009-01-01

    Polymorphisms of glutation-S-transferase (GSTM1, GSTT1 GSTP1) and methylentetrahydrofolate reductase (MTHFR) genes have been studied in DNA from blood lymphocytes of 18 patients with Down's syndrome and 61 controls. Frequencies of normal alleles of GST genotypes were lower in patients as compared to the controls. A DNA analysis of 11 patients and 17 controls revealed the presence of mutations in region 246-250 of exon 7 of the p53 gene in 4 patients. Mutations were not found in the control group. Due to the small sample size, the results of this study should be interpreted with caution and need replication in larger studies.

  5. Polymorphism at codon 36 of the p53 gene.

    PubMed

    Felix, C A; Brown, D L; Mitsudomi, T; Ikagaki, N; Wong, A; Wasserman, R; Womer, R B; Biegel, J A

    1994-01-01

    A polymorphism at codon 36 in exon 4 of the p53 gene was identified by single strand conformation polymorphism (SSCP) analysis and direct sequencing of genomic DNA PCR products. The polymorphic allele, present in the heterozygous state in genomic DNAs of four of 100 individuals (4%), changes the codon 36 CCG to CCA, eliminates a FinI restriction site and creates a BccI site. Including this polymorphism there are four known polymorphisms in the p53 coding sequence.

  6. 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.

  7. LRP5 gene polymorphism and cortical bone.

    PubMed

    Lauretani, Fulvio; Cepollaro, Chiara; Bandinelli, Stefania; Cherubini, Antonio; Gozzini, Alessia; Masi, Laura; Falchetti, Alberto; Del Monte, Francesca; Carbonell-Sala, Silvia; Marini, Francesca; Tanini, Annalisa; Corsi, Anna Maria; Ceda, Gian Paolo; Brandi, Maria Luisa; Ferrucci, Luigi

    2010-08-01

    There is evidence that distinct genetic polymorphisms of LRP5 are associated with low Bone Mineral Density (BMD) and the risk of fracture. However, relationships between LRP5 polymorphisms and micro- and macro architectural bone characteristics assessed by pQCT have not been studied. The aim of the present study was to investigate the association of Ala1330Val and Val667Met polymorphisms in LRP5 gene with volumetric BMD (vBMD) and macro-architectural bone parameters in a population-based sample of men and women. We studied 959 participants of the InCHIANTI study (451 men and 508 women, age range: 21-94 yrs). Trabecular vBMD (vBMDt, mg/cm3), cortical vBMD (vBMDc, mg/cm3), cortical bone area (CBA, mm2) and cortical thickness (Ct.Th, mm) at the level of the tibia were assessed by peripheral quantitative computed tomography (pQCT). Ala1330Val and Val667Met genotypes were determined on genomic DNA by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In age-adjusted analyses both LRP 1330-valine and LRP 667-metionin variants were associated with lower vBMDt in men (p<0.05), and lower vBMDt (p<0.05), Ct.Th (p<0.05) and CBA (p<0.05) in women. After adjusting for multiple confounders, only the association of LRP5 1330-valine and 667-metionin with CBA remained statistically significant (p=0.04 and p=0.01, respectively) in women. These findings suggest that both Ala1330Val and Val667Met LRP5 polymorphisms may affect the determination of geometric bone parameters in women.

  8. LRP5 gene polymorphism and cortical bone

    PubMed Central

    Lauretani, Fulvio; Cepollaro, Chiara; Bandinelli, Stefania; Cherubini, Antonio; Gozzini, Alessia; Masi, Laura; Falchetti, Alberto; Del Monte, Francesca; Carbonell-Sala, Silvia; Marini, Francesca; Tanini, Annalisa; Corsi, Anna Maria; Ceda, Gian Paolo; Brandi, Maria Luisa; Ferrucci, Luigi

    2016-01-01

    Background and aims There is evidence that distinct genetic polymorphisms of LRP5 are associated with low Bone Mineral Density (BMD) and the risk of fracture. However, relationships between LRP5 polymorphisms and micro- and macro-architectural bone characteristics assessed by pQCT have not been studied. The aim of the present study was to investigate the association of Ala1330Val and Val667Met polymorphisms in LRP5 gene with volumetric BMD (vBMD) and macro-architectural bone parameters in a population-based sample of men and women. Methods We studied 959 participants of the InCHIANTI study (451 men and 508 women, age range: 21–94 yrs). Trabecular vBMD (vBMDt, mg/cm3), cortical vBMD (vBMDc, mg/cm3), cortical bone area (CBA, mm2) and cortical thickness (Ct.Th, mm) at the level of the tibia were assessed by peripheral quantitative computed tomography (pQCT). Ala1330Val and Val667Met genotypes were determined on genomic DNA by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results In age-adjusted analyses both LRP 1330-valine and LRP 667-metionin variants were associated with lower vBMDt in men (p<0.05), and lower vBMDt (p<0.05), Ct.Th (p<0.05) and CBA (p<0.05) in women. After adjusting for multiple confounders, only the association of LRP5 1330-valine and 667-metionin with CBA remained statistically significant (p=0.04 and p=0.01, respectively) in women. Conclusion These findings suggest that both Ala1330Val and Val667Met LRP5 polymorphisms may affect the determination of geometric bone parameters in women. PMID:21116122

  9. Adiponectin gene polymorphisms: Association with childhood obesity

    PubMed Central

    Fraga, Vanêssa Gomes; Gomes, Karina Braga

    2014-01-01

    The current childhood obesity epidemic represents a particular challenge for public health. Understanding of the etiological mechanisms of obesity remains integral in treating this complex disorder. In recent years, studies have elucidated the influence of hormones secreted by adipose tissue named adipokines. Adiponectin is a adipokine that exhibits important anti-inflammatory, insulin-sensitizing and anti-atherogenic properties and it is strongly associated to obesity development. It is well known that adiponectin levels decrease with obesity. Furthermore, studies show that some single nucleotide polymorphisms in the gene encoding adiponectin, ADIPOQ, may influence the expression of this protein. The objective of this paper is to provide an up-to-date review of ADIPOQ polymorphisms in the context of childhood obesity. PMID:27625863

  10. Gene Polymorphism Studies in a Teaching Laboratory

    NASA Astrophysics Data System (ADS)

    Shultz, Jeffry

    2009-02-01

    I present a laboratory procedure for illustrating transcription, post-transcriptional modification, gene conservation, and comparative genetics for use in undergraduate biology education. Students are individually assigned genes in a targeted biochemical pathway, for which they design and test polymerase chain reaction (PCR) primers. In this example, students used genes annotated for the steroid biosynthesis pathway in soybean. The authoritative Kyoto encyclopedia of genes and genomes (KEGG) interactive database and other online resources were used to design primers based first on soybean expressed sequence tags (ESTs), then on ESTs from an alternate organism if soybean sequence was unavailable. Students designed a total of 50 gene-based primer pairs (37 soybean, 13 alternative) and tested these for polymorphism state and similarity between two soybean and two pea lines. Student assessment was based on acquisition of laboratory skills and successful project completion. This simple procedure illustrates conservation of genes and is not limited to soybean or pea. Cost per student estimates are included, along with a detailed protocol and flow diagram of the procedure.

  11. Ghrelin gene polymorphisms in rheumatoid arthritis.

    PubMed

    Ozgen, Metin; Koca, Suleyman Serdar; Etem, Ebru Onalan; Yuce, Huseyin; Aydin, Suleyman; Isik, Ahmet

    2011-07-01

    Ghrelin, an endogenous orexigenic peptide, has anti-inflammatory effects, down-regulates pro-inflammatory cytokines, and its altered levels are reported in various inflammatory diseases. The human preproghrelin (ghrelin/obestatin) gene shows several single nucleotide polymorphisms (SNPs) including Arg51Gln, Leu72Met, Gln90Leu, and A-501C. The aim of this study was to investigate the frequency, and clinical significance, of these four SNPs in a small cohort of Turkish patients with rheumatoid arthritis (RA). The study included 103 patients with RA and 103 healthy controls. In the RA group, disease activity and disease-related damage were assessed using the Disease Activity Score-28 (DAS-28), and the modified Larsen scoring (MLS) methods. In all the participants, genomic DNA was isolated and genotyped by polymerase chain reaction and restriction fragment length polymorphism analysis. The frequencies of ghrelin gene SNPs were 82.5 and 79.6% in the RA and control groups, respectively, and there were no significant differences in terms of genotype distributions and allele frequencies for these four SNPs between the groups. However, the A-501C SNP was found to be associated with early disease onset, and Gln90Leu SNP with less frequent rheumatoid factor positivity, in the RA group. A-501C SNP is associated with earlier onset of RA suggesting that genetic variations in the ghrelin gene may have an impact on RA. Copyright © 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  12. [Polymorphic loci and polymorphism analysis of short tandem repeats within XNP gene].

    PubMed

    Liu, Qi-Ji; Gong, Yao-Qin; Guo, Chen-Hong; Chen, Bing-Xi; Li, Jiang-Xia; Guo, Yi-Shou

    2002-01-01

    To select polymorphic short tandem repeat markers within X-linked nuclear protein (XNP) gene, genomic clones which contain XNP gene were recognized by homologous analysis with XNP cDNA. By comparing the cDNA with genomic DNA, non-exonic sequences were identified, and short tandem repeats were selected from non-exonic sequences by using BCM search Launcher. Polymorphisms of the short tandem repeats in Chinese population were evaluated by PCR amplification and PAGE. Five short tandem repeats were identified from XNP gene, two of which were polymorphic. Four and 11 alleles were observed in Chinese population for XNPSTR1 and XNPSTR4, respectively. Heterozygosities were 47% for XNPSTR1 and 70% for XNPSTR4. XNPSTR1 and XNPSTR4 localized within 3' end and intron 10, respectively. Two polymorphic short tandem repeats have been identified within XNP gene and will be useful for linkage analysis and gene diagnosis of XNP gene.

  13. The role of gene polymorphisms in endometriosis

    PubMed Central

    Matalliotakis, Michail; Zervou, Maria I.; Matalliotaki, Charoula; Rahmioglu, Nilufer; Koumantakis, George; Kalogiannidis, Ioannis; Prapas, Ioannis; Zondervan, Krina; Spandidos, Demetrios A.; Matalliotakis, Ioannis; Goulielmos, George N.

    2017-01-01

    Endometriosis is a benign gynecologic disorder, affecting up to 10% of women, characterized by the presence of functional endometrial tissue at ectopic positions generally within the peritoneum. It is a heritable condition influenced by multiple genetic and environmental factors, with an overall heritability estimated at approximately 50%. In this study, we investigated whether single nucleotide polymorphisms (SNPs) rs7521902, rs10859871 and rs11031006, mapping to WNT4, VEZT and FSHB genetic loci, respectively, are associated with risk for endometriosis in a Greek population. This study included 166 women with histologically confirmed endometriosis diagnosed through surgery and 150 normal controls. Genotyping of the rs7521902, rs10859871 and rs11031006 SNPs was performed with Taqman primer/probe sets. A significant association was detected with the AC genotype of rs7521902 (WNT4) in patients with stage III and IV disease only. Evidence for association with endometriosis was also found for the AC genotype of the rs10859871 of VEZT. Notably, a significant difference in the distribution of the AG genotype and the minor allele A of FSHB rs11031006 SNP was found between the endometriosis patients and controls. We found a genetic association between rs11031006 (FSHB) SNP and endometriosis. WNT4 and VEZT genes constitute the most consistently associated genes with endometriosis. In the present study, an association of rs7521902 (WNT4) and rs10859871 (VEZT) was confirmed in women with endometriosis at the genotypic but not the allelic level. PMID:28901453

  14. Association between Tryptophan Hydroxylase 2 Gene Polymorphism and Completed Suicide

    ERIC Educational Resources Information Center

    Fudalej, Sylwia; Ilgen, Mark; Fudalej, Marcin; Kostrzewa, Grazyna; Barry, Kristen; Wojnar, Marcin; Krajewski, Pawel; Blow, Frederic; Ploski, Rafal

    2010-01-01

    The association between suicide and a single nucleotide polymorphism (rs1386483) was examined in the recently identified tryptophan hydroxylase 2 (TPH2) gene. Blood samples of 143 suicide victims and 162 age- and sex-matched controls were examined. The frequency of the TT genotype in the TPH2 polymorphism was higher in suicide victims than in…

  15. Are "functionally related polymorphisms" of renin-angiotensin-aldosterone system gene polymorphisms associated with hypertension?

    PubMed

    Hahntow, Ines N; Mairuhu, Gideon; van Valkengoed, Irene Gm; Koopmans, Richard P; Michel, Martin C

    2010-06-02

    Genotype-phenotype association studies are typically based upon polymorphisms or haplotypes comprised of multiple polymorphisms within a single gene. It has been proposed that combinations of polymorphisms in distinct genes, which functionally impact the same phenotype, may have stronger phenotype associations than those within a single gene. We have tested this hypothesis using genes encoding components of the renin-angiotensin-aldosterone system and the high blood pressure phenotype. Our analysis is based on 1379 participants of the cross-sectional SUNSET study randomly selected from the population register of Amsterdam. Each subject was genotyped for the angiotensinogen M235T, the angiotensin-converting enzyme insertion/deletion and the angiotensin II type 1 receptor A1166C polymorphism. The phenotype high blood pressure was defined either as a categorical variable comparing hypertension versus normotension as in most previous studies or as a continuous variable using systolic, diastolic and mean blood pressure in a multiple regression analysis with gender, ethnicity, age, body-mass-index and antihypertensive medication as covariates. Genotype-phenotype relationships were explored for each polymorphism in isolation and for double and triple polymorphism combinations. At the single polymorphism level, only the A allele of the angiotensin II type 1 receptor was associated with a high blood pressure phenotype. Using combinations of polymorphisms of two or all three genes did not yield stronger/more consistent associations. We conclude that combinations of physiologically related polymorphisms of multiple genes, at least with regard to the renin-angiotensin-aldosterone system and the hypertensive phenotype, do not necessarily offer additional benefit in analyzing genotype/phenotype associations.

  16. Cytokine gene polymorphisms in bullous pemphigoid in a Chinese population.

    PubMed

    Chang, Y T; Liu, H N; Yu, C W; Lin, M W; Huang, C H; Chen, C C; Liu, M T; Lee, D D; Wang, W J; Tsai, S F

    2006-01-01

    Bullous pemphigoid (BP) is an autoimmune bullous disease mostly associated with autoantibodies to the hemidesmosomal BP autoantigens BP180 and BP230. High levels of interleukin (IL)-1beta, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma have been detected in skin lesions or sera of patients with BP. Cytokine gene polymorphisms may affect cytokine production and contribute to susceptibility to autoimmune diseases. Until now, no cytokine gene polymorphism study has been conducted on patients with BP. We aimed to determine whether the genetic polymorphisms of the cytokine genes might influence the development of BP. DNA samples were obtained from 96 BP patients and 174 control subjects. Using direct sequencing and microsatellite genotyping, we examined 23 polymorphisms in 11 cytokine genes including the IL-1alpha, IL-1beta, IL-1 receptor antagonist, IL-4, IL-6, IL-8, IL-10, IL-13, IL-4 receptor, TNF-alpha and IFN-gamma genes. Although the BP patients were more likely to carry the -511T and -31C alleles of the IL-1beta gene (P = 0.04), the significance disappeared after correction for multiple testing (Pc). There was complete linkage disequilibrium between the -511T and -31C alleles of the IL-1beta gene. In female patients with BP, the associations with IL-1beta (-511T) and (-31C) alleles were much stronger (68% vs. 40.6%, odds ratio = 3.11, Pc = 0.006). No significantly different allelic and genotypic distributions of other cytokine gene polymorphisms could be found between the patients with BP and controls. Moreover, no association with the extent of disease involvement (localized or generalized) was observed. The IL-1beta (-511) and (-31) polymorphisms were significantly associated with BP in women. The other genetic polymorphisms of cytokine genes that we analysed do not appear to be associated with BP susceptibility in our Chinese population.

  17. TRPA1 gene polymorphisms and childhood asthma.

    PubMed

    Gallo, Valentina; Dijk, F Nicole; Holloway, John W; Ring, Susan M; Koppelman, Gerard H; Postma, Dirkje S; Strachan, David P; Granell, Raquel; de Jongste, Johan C; Jaddoe, Vincent W V; den Dekker, Herman T; Duijts, Liesbeth; Henderson, A John; Shaheen, Seif O

    2017-03-01

    Animal data have suggested that the transient receptor potential ankyrin-1 (TRPA1) ion channel plays a key role in promoting airway inflammation in asthma and may mediate effects of paracetamol on asthma, yet confirmatory human data are lacking. To study associations of TRPA1 gene variants with childhood asthma and total IgE concentration, and interactions between TRPA1 and prenatal paracetamol exposure on these outcomes. We analysed associations between 31 TRPA1 single nucleotide polymorphisms (SNPs) and current doctor-diagnosed asthma and total IgE concentration at 7.5 years in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. We sought to confirm the most significant associations with comparable outcomes in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) and Generation R birth cohorts. In ALSPAC, we explored interactions with prenatal paracetamol exposure. In ALSPAC, there was strong evidence for association between six SNPs and asthma: rs959974 and rs1384001 (per-allele odds ratio for both: 1.30 (95% CI: 1.15-1.47), p = 0.00001), rs7010969 (OR 1.28 (1.13-1.46), p = 0.00004), rs3735945 (OR 1.30 (1.09-1.55), p = 0.003), rs920829 (OR 1.30 (1.09-1.54), p = 0.004) and rs4738202 (OR 1.22 (1.07-1.39), p = 0.004). In a meta-analysis across the three cohorts, the pooled effect estimates confirmed that all six SNPs were significantly associated with asthma. In ALSPAC, TRPA1 associations with asthma were not modified by prenatal paracetamol, although associations with IgE concentration were. This study suggests that TRPA1 may play a role in the development of childhood asthma. (249 words). © 2016 The Authors Pediatric Allergy and Immunology Published by John Wiley & Sons Ltd.

  18. 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.

  19. Association of -330 interleukin-2 gene polymorphism with oral cancer.

    PubMed

    Singh, Prithvi Kumar; Kumar, Vijay; Ahmad, Mohammad Kaleem; Gupta, Rajni; Mahdi, Abbas Ali; Jain, Amita; Bogra, Jaishri; Chandra, Girish

    2017-12-01

    Cytokines play an important role in the development of cancer. Several single-nucleotide polymorphisms (SNPs) of cytokine genes have been reported to be associated with the development and severity of inflammatory diseases and cancer predisposition. This study was undertaken to evaluate a possible association of interleukin 2 (IL-2) (- 330A>C) gene polymorphisms with the susceptibility to oral cancer. The SNP in IL-2 (-330A>C) gene was genotyped in 300 oral cancer patients and in similar number of healthy volunteers by polymerase chain reaction (PCR)-restriction fragment length polymorphism and the association of the gene with the disease was evaluated. IL-2 (-330A>C) gene polymorphism was significantly associated with oral cancer whereas it was neither associated with clinicopathological status nor with cancer pain. The AC heterozygous genotype was significantly associated with oral cancer patients as compared to controls [odds ratio (OR): 3.0; confidence interval (CI): 2.14-4.20; P<0.001]. The C allele frequency was also significantly associated with oral cancer (OR: 1.80; CI: 1.39-2.33; P<0.001). IL-2 (-330A>C) gene polymorphism was also associated with oral cancer in tobacco smokers and chewers. Our results showed that oral cancer patients had significantly higher frequency of AA genotype but significantly lower frequency of AC genotype and C allele compared to controls. The IL-2 AC genotype and C allele of IL-2 (-330A>C) gene polymorphisms could be potential protective factors and might reduce the risk of oral cancer in Indian population.

  20. Inflammatory bowel disease: the role of inflammatory cytokine gene polymorphisms.

    PubMed Central

    Balding, Joanna; Livingstone, Wendy J; Conroy, Judith; Mynett-Johnson, Lesley; Weir, Donald G; Mahmud, Nasir; Smith, Owen P

    2004-01-01

    The mechanisms responsible for development of inflammatory bowel disease (IBD) have not been fully elucidated, although the main cause of disease pathology is attributed to up-regulated inflammatory processes. The aim of this study was to investigate frequencies of polymorphisms in genes encoding pro-inflammatory and anti-inflammatory markers in IBD patients and controls. We determined genotypes of patients with IBD (n= 172) and healthy controls (n= 389) for polymorphisms in genes encoding various cytokines (interleukin (IL)-1beta, IL-6, tumour necrosis factor (TNF), IL-10, IL-1 receptor antagonist). Association of these genotypes to disease incidence and pathophysiology was investigated. No strong association was found with occurrence of IBD. Variation was observed between the ulcerative colitis study group and the control population for the TNF-alpha-308 polymorphism (p= 0.0135). There was also variation in the frequency of IL-6-174 and TNF-alpha-308 genotypes in the ulcerative colitis group compared with the Crohn's disease group (p= 0.01). We concluded that polymorphisms in inflammatory genes are associated with variations in IBD phenotype and disease susceptibility. Whether the polymorphisms are directly involved in regulating cytokine production, and consequently pathophysiology of IBD, or serve merely as markers in linkage disequilibrium with susceptibility genes remains unclear. PMID:15223609

  1. Depressive symptoms in schizophrenia and dopamine and serotonin gene polymorphisms.

    PubMed

    Peitl, Vjekoslav; Štefanović, Mario; Karlović, Dalibor

    2017-07-03

    Although depressive symptoms seem to be frequent in schizophrenia they have received significantly less attention than other symptom domains. As impaired serotonergic and dopaminergic neurotransmission is implicated in the pathogenesis of depression and schizophrenia this study sought to investigate the putative association between several functional gene polymorphisms (SERT 5-HTTLPR, MAO-A VNTR, COMT Val158Met and DAT VNTR) and schizophrenia. Other objectives of this study were to closely examine schizophrenia symptom domains by performing factor analysis of the two most used instruments in this setting (Positive and negative syndrome scale - PANSS and Calgary depression rating scale - CDSS) and to examine the influence of investigated gene polymorphisms on the schizophrenia symptom domains, focusing on depressive scores. A total of 591 participants were included in the study (300 schizophrenic patients and 291 healthy volunteers). 192 (64%) of schizophrenic patients had significant depressive symptoms. Genotype distribution revealed no significant differences regarding all investigated polymorphisms except the separate gender analysis for MAO-A gene polymorphism which revealed significantly more allele 3 carriers in schizophrenic males. Factor analysis of the PANSS scale revealed the existence of five separate factors (symptom domains), while the CDSS scale revealed two distinct factors. Several investigated gene polymorphisms (mostly SERT and MAO-A, but also COMT) significantly influenced two factors from the PANSS (aggressive/impulsive and negative symptoms) and one from the CDSS scale (suicidality), respectively. Depressive symptoms in schizophrenic patients may be influenced by functional gene polymorphisms, especially those implicated in serotonergic neurotransmission. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Serotonin transporter gene polymorphisms and hyperserotonemia in autistic disorder.

    PubMed

    Betancur, C; Corbex, M; Spielewoy, C; Philippe, A; Laplanche, J L; Launay, J M; Gillberg, C; Mouren-Siméoni, M C; Hamon, M; Giros, B; Nosten-Bertrand, M; Leboyer, M

    2002-01-01

    Previous studies have provided conflicting evidence regarding the association of the serotonin transporter (5-HTT) gene with autism. Two polymorphisms have been identified in the human 5-HTT gene, a VNTR in intron 2 and a functional deletion/insertion in the promoter region (5-HTTLPR) with short and long variants. Positive associations of the 5-HTTLPR polymorphism with autism have been reported by two family-based studies, but one found preferential transmission of the short allele and the other of the long allele. Two subsequent studies failed to find evidence of transmission disequilibrium at the 5-HTTLPR locus. These conflicting results could be due to heterogeneity of clinical samples with regard to serotonin (5-HT) blood levels, which have been found to be elevated in some autistic subjects. Thus, we examined the association of the 5-HTTLPR and VNTR polymorphisms of the 5-HTT gene with autism, and we investigated the relationship between 5-HTT variants and whole-blood 5-HT. The transmission/disequilibrium test (TDT) revealed no linkage disequilibrium at either loci in a sample of 96 families comprising 43 trios and 53 sib pairs. Furthermore, no significant relationship between 5-HT blood levels and 5-HTT gene polymorphisms was found. Our results suggest that the 5-HTT gene is unlikely to play a major role as a susceptibility factor in autism.

  3. Serotonin transporter gene polymorphisms and hyperserotonemia in autistic disorder

    PubMed Central

    Betancur, Catalina; Corbex, Marylis; Spielewoy, Cécile; Philippe, Anne; Laplanche, Jean-Louis; Launay, Jean-Marie; Gillberg, Christopher; Mouren-Simeoni, Marie-Christine; Hamon, Michel; Giros, Bruno; Nosten-Bertrand, Marika; Leboyer, Marion

    2002-01-01

    Previous studies have provided conflicting evidence regarding the association of the serotonin transporter (5-HTT) gene with autism. Two polymorphisms have been identified in the human 5-HTT gene, a VNTR in intron 21 and a functional deletion/insertion in the promoter region (5-HTTLPR) with short and long variants.2 Positive associations of the 5-HTTLPR polymorphism with autism have been reported by two family-based studies, but one found preferential transmission of the short allele3 and the other of the long allele.4 Two subsequent studies failed to find evidence of transmission disequilibrium at the 5-HTTLPR locus.5,6 These conflicting results could be due to heterogeneity of clinical samples with regard to serotonin (5-HT) blood levels, which have been found to be elevated in some autistic subjects.7–9 Thus, we examined the association of the 5-HTTLPR and VNTR polymorphisms of the 5-HTT gene with autism, and we investigated the relationship between 5-HTT variants and whole-blood 5-HT. The transmission/disequilibrium test (TDT) revealed no linkage disequilibrium at either loci in a sample of 96 families comprising 43 trios and 53 sib pairs. Furthermore, no significant relationship between 5-HT blood levels and 5-HTT gene polymorphisms was found. Our results suggest that the 5-HTT gene is unlikely to play a major role as a susceptibility factor in autism. PMID:11803447

  4. Vitiligo susceptibility and catalase gene (CAT) polymorphisms in sicilian population.

    PubMed

    Caputo, Valentina; Niceta, Marcello; Fiorella, Santi; La Vecchia, Marco; Bastonini, Emanuela; Bongiorno, Maria R; Pistone, Giuseppe

    2017-02-15

    Catalase gene (CAT) polymorphisms were analyzed as responsible for the deficiency of catalase enzyme activity and concomitant accumulation of excessive hydrogen peroxide in Vitiligo patients. Catalase is a well known oxidative stress regulator that could play an important role in the pathogenesis of Vitiligo. This study was conducted to evaluate three CAT gene polymorphisms (-89A/T, 389C/T, 419C/T) and their association with Vitiligo susceptibility in Sicilian population. 60 out of 73 Sicilian patients with Vitiligo were enrolled and submitted to CAT gene analysis. Contrary to the Northern part of Europe but likewise to the Mediterranean area, the frequency of the CAT genotypes in Sicily is equally distributed. Out of all CAT genotypes, only CAT -89 T/T frequency was found to be significantly higher amongst Vitiligo patients than controls. Despite the involvement of the CAT enzyme in the pathogenesis of Vitiligo, the biological significance of CAT gene polymorphisms is still controversial. With the only exception for CAT variant -89A/T, the other studied CAT gene polymorphisms (389C/T and 419C/T) might not to be associated with Vitiligo in Sicilian population.

  5. Relationship of MTHFR gene polymorphisms with renal and cardiac disease

    PubMed Central

    Trovato, Francesca M; Catalano, Daniela; Ragusa, Angela; Martines, G Fabio; Pirri, Clara; Buccheri, Maria Antonietta; Di Nora, Concetta; Trovato, Guglielmo M

    2015-01-01

    AIM: To investigate the effects of different methylenetetrahydrofolate reductase (MTHFR) 677C>T gene polymorphism and hyperhomocysteinemia for the development of renal failure and cardiovascular events, which are controversial. METHODS: We challenged the relationship, if any, of MTHFR 677C>T and MTHFR 1298A>C polymorphisms with renal and heart function. The present article is a reappraisal of these concepts, investigating within a larger population, and including a subgroup of dialysis patients, if the two most common MTHFR polymorphisms, C677T and A1298C, as homozygous, heterozygous or with a compound heterozygous state, show different association with chronic renal failure requiring hemodialysis. MTHFR polymorphism could be a favorable evolutionary factor, i.e., a protective factor for many ominous conditions, like cancer and renal failure. A similar finding was reported in fatty liver disease in which it is suggested that MTHFR polymorphisms could have maintained and maintain their persistence by an heterozygosis advantage mechanism. We studied a total of 630 Italian Caucasian subject aged 54.60 ± 16.35 years, addressing to the increased hazard of hemodialysis, if any, according to the studied MTHFR genetic polymorphisms. RESULTS: A favorable association with normal renal function of MTHFR polymorphisms, and notably of MTHFR C677T is present independently of the negative effects of left ventricular hypertrophy, increased Intra-Renal arterial Resistance and hyperparathyroidism. CONCLUSION: MTHFR gene polymorphisms could have a protective role on renal function as suggested by their lower frequency among our dialysis patients in end-stage renal failure; differently, the association with left ventricular hypertrophy and reduced left ventricular relaxation suggest some type of indirect, or concurrent mechanism. PMID:25664255

  6. Opsin gene polymorphism predicts trichromacy in a cathemeral lemur.

    PubMed

    Veilleux, Carrie C; Bolnick, Deborah A

    2009-01-01

    Recent research has identified polymorphic trichromacy in three diurnal strepsirrhines: Coquerel's sifaka (Propithecus coquereli), black and white ruffed lemurs (Varecia variegata), and red ruffed lemurs (V. rubra). Current hypotheses suggest that the transitions to diurnality experienced by Propithecus and Varecia were necessary precursors to their independent acquisitions of trichromacy. Accordingly, cathemeral lemurs are thought to lack the M/L opsin gene polymorphism necessary for trichromacy. In this study, the M/L opsin gene was sequenced in ten cathemeral blue-eyed black lemurs (Eulemur macaco flavifrons). This analysis identified a polymorphism identical to that of other trichromatic strepsirrhines at the critical amino acid position 285 in exon 5 of the M/L opsin gene. Thus, polymorphic trichromacy is likely present in at least one cathemeral Eulemur species, suggesting that strict diurnality is not necessary for trichromacy. The presence of trichromacy in E. m. flavifrons suggests that a re-evaluation of current hypotheses regarding the evolution of strepsirrhine trichromacy may be necessary. Although the M/L opsin polymorphism may have been independently acquired three times in the lemurid-indriid clade, the distribution of opsin alleles in lemurids and indriids may also be consistent with a common origin of trichromacy in the last common ancestor of either the lemurids or the lemurid-indriid clade. (c) 2008 Wiley-Liss, Inc.

  7. PD-1 gene polymorphism in children with subacute sclerosing panencephalitis.

    PubMed

    Piskin, Ibrahim Etem; Calık, Mustafa; Abuhandan, Mahmut; Kolsal, Ebru; Celik, Sevim Karakas; Iscan, Akın

    2013-08-01

    Subacute sclerosing panencephalitis (SSPE) is a progressive inflammatory and degenerative disorder of the central nervous system. Several factors influence the risk of chronic brain infection with the mutant measles virus. However, to date, no pathogenic mechanism that may predispose to SSPE has been determined. Studies have indicated that specific polymorphisms in certain host genes are probably involved in impairing the ability of host immune cells to eradicate the measles virus in SSPE patients. Programmed cell death protein 1 (PD-1), a member of the CD28 family, is a negative regulator of the immune system. The purpose of our study was to investigate whether PD-1 gene polymorphisms affect susceptibility to the development of SSPE in Turkish children. In total, 109 subjects (54 SSPE patients and 55 healthy controls) were genotyped for the PD-1.9 C/T (rs2227982) single-nucleotide polymorphism (SNP). The distributions of T alleles in the PD-1.9 polymorphism in SSPE patients and healthy controls were 2.8 and 10.9%, respectively. There was a statistically significant difference between the groups; the 95% confidence interval (CI) was 0.06 to 0.85 and the odds ratio (OR) was 0.23 (χ(2) test). Thus, we identified an association between SSPE and the PD-1 rs2227982 gene polymorphism; the frequency of T alleles was higher in controls than in SSPE patients. Georg Thieme Verlag KG Stuttgart · New York.

  8. Effect of Cytokine Signaling 3 Gene Polymorphisms in Childhood Obesity.

    PubMed

    Boyraz, Mehmet; Yeşilkaya, Ediz; Ezgü, Fatih; Bideci, Aysun; Doğan, Haldun; Ulucan, Korkut; Cinaz, Peyami

    2016-12-01

    Although polymorphisms in suppressor of cytokine signaling 3 (SOCS3) was reported to be related to obesity, Metabolic syndrome (MS), and type 2 diabetes mellitus in various adult studies, there is a lack of data in children. In this study, we examined eight reported polymorphisms of SOCS3 in obese Turkish children and adolescent with and without MS and compared the results with that of controls. One hundred and forty eight obese and 63 age- and sex-matched control subjects were enrolled in the study. Obesity classification was carried out according to body mass index. World Health Organization and National Cholesterol Education Program criteria were used for the diagnosis of MS. Genotyping procedure was carried out by polymerase chain reaction and Sanger sequencing protocol. The frequency of rs2280148 polymorphism was significantly higher in obese subjects with MS than in the control group, whereas the frequency of rs8064821 polymorphism was significantly higher in obese subjects with MS than in obese children without MS. The significant associations of certain SOCS3 polymorphisms with obesity parameters in both MS and MS -related insulin resistance, hypertension, and fatty liver suggest that polymorphisms in this gene may play a role in the pathogenesis of MS and also that they can be potentially used as a marker for attenuated or aggressive disease.

  9. Gene Polymorphism Studies in a Teaching Laboratory

    ERIC Educational Resources Information Center

    Shultz, Jeffry

    2009-01-01

    I present a laboratory procedure for illustrating transcription, post-transcriptional modification, gene conservation, and comparative genetics for use in undergraduate biology education. Students are individually assigned genes in a targeted biochemical pathway, for which they design and test polymerase chain reaction (PCR) primers. In this…

  10. Gene polymorphisms of fibrinolytic enzymes in coal workers' pneumoconiosis

    SciTech Connect

    Chang, L.C.; Tseng, J.C.; Hua, C.C.

    2006-03-15

    The authors assessed the gene polymorphisms of missense C/T polymorphism in exon 6 of the urokinase-plasminogen activator (PLAU) gene (PLAU P141L), A/u-repeat in intron 8 of the tissue-type plasminogen activator (PLAT) gene (PLAT TPA25 Alu insertion), and 4G/5G in the promoter region of the serine proteinase inhibitor, clade E (SERPINE) or plasminogen activator inhibitor type 1 gene (SERPINE1 -675 4G/5G) in 153 healthy volunteers and 154 retired coal miners with coal miners' pneumoconiosis (CWP). The CWP subjects included 94 individuals with simple pneumoconiosis and 60 individuals with progressive massive fibrosis presenting with worse pulmonary function. The distributions of genotypes ofmore » these three genes did not differ between the control and CWP subjects or between subjects with simple pneumoconiosis and those with progressive massive fibrosis. However, by assessing duration of work and its interaction with genotypes by means of logistic regression, the authors found the missense C/T polymorphism in exon 6 of the PLAU gene to be an effect modifier of the association between work duration and the development of progressive massive fibrosis.« less

  11. Polymorphic human somatostatin gene is located on chromosome 3.

    PubMed Central

    Naylor, S L; Sakaguchi, A Y; Shen, L P; Bell, G I; Rutter, W J; Shows, T B

    1983-01-01

    Somatostatin is a 14-amino-acid neuropeptide and hormone that inhibits the secretion of several peptide hormones. The human gene for somatostatin SST has been cloned, and the sequence has been determined. This clone was used as a probe in chromosome mapping studies to detect the human somatostatin sequence in human-rodent hybrids. Southern blot analysis of 41 hybrids, including some containing translocations of human chromosomes, placed SST in the q21 leads to qter region of chromosome 3. Human DNAs from unrelated individuals were screened for restriction fragment polymorphisms detectable by the somatostatin gene probe. Two polymorphisms were found: (i) an EcoRI variant located at the 3' end of the gene, found in Caucasian, U.S. Black, and Asian populations with a frequency of approximately 0.10 and (ii) a BamHI variant in the intron, which occurs in Caucasians at a frequency of 0.13. Images PMID:6133281

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

    PubMed

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

    2010-01-01

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

  13. Gene-gene interactions and gene polymorphisms of VEGFA and EG-VEGF gene systems in recurrent pregnancy loss.

    PubMed

    Su, Mei-Tsz; Lin, Sheng-Hsiang; Chen, Yi-Chi; Kuo, Pao-Lin

    2014-06-01

    Both vascular endothelial growth factor A (VEGFA) and endocrine gland-derived vascular endothelial growth factor (EG-VEGF) systems play major roles in angiogenesis. A body of evidence suggests VEGFs regulate critical processes during pregnancy and have been associated with recurrent pregnancy loss (RPL). However, little information is available regarding the interaction of these two major major angiogenesis-related systems in early human pregnancy. This study was conducted to investigate the association of gene polymorphisms and gene-gene interaction among genes in VEGFA and EG-VEGF systems and idiopathic RPL. A total of 98 women with history of idiopathic RPL and 142 controls were included, and 5 functional SNPs selected from VEGFA, KDR, EG-VEGF (PROK1), PROKR1 and PROKR2 were genotyped. We used multifactor dimensionality reduction (MDR) analysis to choose a best model and evaluate gene-gene interactions. Ingenuity pathways analysis (IPA) was introduced to explore possible complex interactions. Two receptor gene polymorphisms [KDR (Q472H) and PROKR2 (V331M)] were significantly associated with idiopathic RPL (P<0.01). The MDR test revealed that the KDR (Q472H) polymorphism was the best loci to be associated with RPL (P=0.02). IPA revealed EG-VEGF and VEGFA systems shared several canonical signaling pathways that may contribute to gene-gene interactions, including the Akt, IL-8, EGFR, MAPK, SRC, VHL, HIF-1A and STAT3 signaling pathways. Two receptor gene polymorphisms [KDR (Q472H) and PROKR2 (V331M)] were significantly associated with idiopathic RPL. EG-VEGF and VEGFA systems shared several canonical signaling pathways that may contribute to gene-gene interactions, including the Akt, IL-8, EGFR, MAPK, SRC, VHL, HIF-1A and STAT3.

  14. Interleukin-1beta gene polymorphisms in Taiwanese patients with gout.

    PubMed

    Chen, Man-Ling; Huang, Chung-Ming; Tsai, Chang-Hai; Tsai, Fuu-Jen

    2005-04-01

    The purpose of this study was to examine whether interleukin-1 beta (IL-1beta) promoter and exon 5 gene polymorphisms are markers of susceptibility or clinical manifestations in Taiwanese patients with gout. The study included 196 patients in addition to 103 unrelated healthy control subjects living in central Taiwan. From genomic DNA, polymorphisms of the gene for IL-1beta promoter and IL-1beta exon 5 were typed. Allelic frequencies were compared between the two groups, and the relationship between allelic frequencies and clinical manifestations of gout was evaluated. No significant differences were observed in the allelic frequencies of the IL-1beta promoter between patients with gout and healthy control subjects. Additionally, we did not detect any association of the IL-1beta promoter genotype with the clinical and laboratory profiles of gout patients. However, there was a significant difference between the two groups in terms of hypertriglyceridemia (P=0.0004, chi(2)=12.52, OR 7.14, 95%CI 0.012-0.22). There was also a significant difference in the genotype of IL-1beta exon 5 polymorphism between patients with and without hypertriglyceridemia. Results of the present study suggest that polymorphisms of the IL-1beta promoter and IL-1beta exon 5 are not related to gout patients in central Taiwan.

  15. Vitamin D Receptor Gene Polymorphisms Associated with Childhood Autism

    PubMed Central

    Cieślińska, Anna; Kostyra, Elżbieta; Chwała, Barbara; Moszyńska-Dumara, Małgorzata; Fiedorowicz, Ewa; Teodorowicz, Małgorzata

    2017-01-01

    Background: Autism spectrum disorder (ASD) is a group of heterogeneous, behaviorally defined disorders whereby currently no biological markers are common to all affected individuals. A deregulated immune response may be contributing to the etiology of ASD. The active metabolite of vitamin D3 has an immunoregulatory role mediated by binding to the vitamin D receptor (VDR) in monocyte, macrophages, and lymphocytes. The effects of vitamin D and interaction with the VDR may be influenced by polymorphism in the VDR gene. Methods: Genetic association of four different VDR polymorphisms (Apa-I, Bsm-I, Taq-I, Fok-I) associated with susceptibility to the development of autism in children was investigated. Results: We uniquely found an association between the presence of the T allele at position Taq-I and presence of the a allele at position Apa-I of the VDR gene with decreased ASD incidence. There was also an association between female gender and the presence of the T allele. We found no statistical significant correlation between VDR single nucleotide polymorphisms (SNPs) and vitamin D3 concentration in serum of ASD children. Conclusion: Genetic polymorphism in two SNP in VDR may be correlated with development of ASD symptoms by influencing functionality of vitamin D3 metabolism, while vitamin D3 levels were not significantly different between ASD and non-ASD children. PMID:28891930

  16. Vitamin D Receptor Gene Polymorphisms Associated with Childhood Autism.

    PubMed

    Cieślińska, Anna; Kostyra, Elżbieta; Chwała, Barbara; Moszyńska-Dumara, Małgorzata; Fiedorowicz, Ewa; Teodorowicz, Małgorzata; Savelkoul, Huub F J

    2017-09-09

    Autism spectrum disorder (ASD) is a group of heterogeneous, behaviorally defined disorders whereby currently no biological markers are common to all affected individuals. A deregulated immune response may be contributing to the etiology of ASD. The active metabolite of vitamin D₃ has an immunoregulatory role mediated by binding to the vitamin D receptor (VDR) in monocyte, macrophages, and lymphocytes. The effects of vitamin D and interaction with the VDR may be influenced by polymorphism in the VDR gene. Genetic association of four different VDR polymorphisms (Apa-I, Bsm-I, Taq-I, Fok-I) associated with susceptibility to the development of autism in children was investigated. We uniquely found an association between the presence of the T allele at position Taq-I and presence of the a allele at position Apa-I of the VDR gene with decreased ASD incidence. There was also an association between female gender and the presence of the T allele. We found no statistical significant correlation between VDR single nucleotide polymorphisms (SNPs) and vitamin D₃ concentration in serum of ASD children. Genetic polymorphism in two SNP in VDR may be correlated with development of ASD symptoms by influencing functionality of vitamin D₃ metabolism, while vitamin D₃ levels were not significantly different between ASD and non-ASD children.

  17. Folate and Breast Cancer: Role of Intake, Blood Levels, and Metabolic Gene Polymorphisms

    DTIC Science & Technology

    2006-06-01

    polymorphisms . The specific aims are 1) methodological training in the analysis of gene - gene and gene -environment interactions by studying folate...evaluation of folate intake, plasma folate, and metabolic gene polymorphisms in relation to breast cancer risk: Months 1-19. b. Prepare blood samples...isolated for the folate and gene polymorphism assays among the 184 cases and matched controls. The folate assays are on-going at this time and over

  18. Interleukin 17 receptor gene polymorphism in periimplantitis and chronic periodontitis.

    PubMed

    Kadkhodazadeh, Mahdi; Ebadian, Ahmad Reza; Amid, Reza; Youssefi, Navid; Mehdizadeh, Amir Reza

    2013-07-13

    Gene polymorphism of cytokines influencing their function has been known as a contributing factor in the pathogenesis of inflammatory diseases of the tooth and implant supporting tissues. The aim of this study was to investigate the association of IL-17R gene polymorphism (rs879576) with chronic periodontitis and periimplantitis in an Iranian population. 73 patients with chronic periodontitis, 37 patients with periimplantitis and 83 periodontally healthy patients were enrolled in this study. 5cc blood was obtained from each subject's arm vein and transferred to 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. Chi-square and Kruskal Wallis tests were used to analyze differences in the expression of genotypes and frequency of alleles in disease and control groups (P-Value less than 0.05 was considered statistically significant). There were no significant differences between periodontitis, periimplantitis with AA, GG, GA genotype of IL-17R gene (P=0.8239). Also comparison of frequency of alleles in SNP rs879576 of IL-17R gene between the chronic periodontitis group and periimplantitis group did not revealed statistically significant differences (P=0.8239). The enigma of IL-17 and its polymorphism-role in periodontitis and periimplantitis is yet to be investigated more carefully throughout further research but this article demonstrates that polymorphism of IL-17R plays no significant role in incidence of chronic periodontitis and Periimplantitis.

  19. Effect of gene polymorphisms on periodontal diseases

    PubMed Central

    Tarannum, Fouzia; Faizuddin, Mohamed

    2012-01-01

    Periodontal diseases are inflammatory diseases of supporting structures of the tooth. It results in the destruction of the supporting structures and most of the destructive processes involved are host derived. The processes leading to destruction and regeneration of the destroyed tissues are of great interest to both researchers and clinicians. The selective susceptibility of subjects for periodontitis has remained an enigma and wide varieties of risk factors have been implicated for the manifestation and progression of periodontitis. Genetic factors have been a new addition to the list of risk factors for periodontal diseases. With the availability of human genome sequence and the knowledge of the complement of the genes, it should be possible to identify the metabolic pathways involved in periodontal destruction and regeneration. Most forms of periodontitis represent a life-long account of interactions between the genome, behaviour, and environment. The current practical utility of genetic knowledge in periodontitis is limited. The information contained within the human genome can potentially lead to a better understanding of the control mechanisms modulating the production of inflammatory mediators as well as provides potential therapeutic targets for periodontal disease. Allelic variants at multiple gene loci probably influence periodontitis susceptibility. PMID:22754216

  20. Genetic polymorphisms of cytokine genes in type 2 diabetes mellitus

    PubMed Central

    Banerjee, Monisha; Saxena, Madhukar

    2014-01-01

    Diabetes mellitus is a combined metabolic disorder which includes hyperglycemia, dyslipidemia, stroke and several other complications. Various groups all over the world are relentlessly working out the possible role of a vast number of genes associated with type 2 diabetes (T2DM). Inflammation is an important outcome of any kind of imbalance in the body and is therefore an indicator of several diseases, including T2DM. Various ethnic populations around the world show different levels of variations in single nucleotide polymorphisms (SNPs). The present review was undertaken to explore the association of cytokine gene polymorphisms with T2DM in populations of different ethnicities. This will lead to the understanding of the role of cytokine genes in T2DM risk and development. Association studies of genotypes of SNPs present in cytokine genes will help to identify risk haplotype(s) for disease susceptibility by developing prognostic markers and alter treatment strategies for T2DM and related complications. This will enable individuals at risk to take prior precautionary measures and avoid or delay the onset of the disease. Future challenges will be to understand the genotypic interactions between SNPs in one cytokine gene or several genes at different loci and study their association with T2DM. PMID:25126395

  1. Malassezia Yeast and Cytokine Gene Polymorphism in Atopic Dermatitis

    PubMed Central

    Das, Shukla; Ramachandran, V.G.; Saha, Rumpa; Bhattacharya, S.N.; Dar, Sajad

    2017-01-01

    Introduction Atopic Dermatitis (AD) is a recurrent chronic condition associated with microorganism and their interaction with the susceptible host. Malassezia yeast is a known commensal which is thought to provoke the recurrent episodes of symptoms in atopic dermatitis patients. Malassezia immunomodulatory properties along with defective skin barrier in such host, results in disease manifestation. Here, we studied Single Nucleotide Polymorphism (SNP) in IL10 and IFN γ genes of the host and its relation with susceptibility to Malassezia infection. Aim To isolate Malassezia yeast from AD patients and compare the genetic susceptibility of the host by correlating the cytokine gene polymorphism with the control subjects. Materials and Methods Study was conducted from January 2012 to January 2013. It was a prospective observational study done in Department of Microbiology and Department of Dermatology and Venereology in University College of Medical Sciences and GTB Hospital, Delhi. Sample size comprised of 38 cases each of AD. Skin scrapings were used for fungal culture on Sabouraud Dextrose Agar (SDA) and Modified Dixon Agar (MDA) and isolated were identified as per conventional phenotypic methods. Genomic DNA was extracted from blood samples collected from all study subjects. Cytokine genotyping was carried out by Amplification Refractory Mutations System- Polymerase Chain Reaction (ARMS-PCR) with sequence specific primers. Three SNPs (IL10-1082A/G; IL10-819/592C/T; IFN-γ+874A/T) in two cytokine genes were assessed in all the patients and healthy controls. Statistical Analysis Chi-Square Test or Fisher’s-Exact Test and Bonferroni’s correction. Results In AD group, Malassezia yeasts were cultured in 24 out of 38 samples and thus the identification rate was 63.1 percent as compared to healthy group, 52.6 percent (20/38). Significant difference in allele, or genotype distribution were observed in IL10-819/592C/T and IFN-γ+874A/T gene polymorphism in AD group

  2. Do polymorphisms in chemosensory genes matter for human ingestive behavior?

    PubMed Central

    Hayes, John E.; Feeney, Emma L.; Allen, Alissa L.

    2013-01-01

    In the last decade, basic research in chemoreceptor genetics and neurobiology have revolutionized our understanding of individual differences in chemosensation. From an evolutionary perspective, chemosensory variations appear to have arisen in response to different living environments, generally in the avoidance of toxins and to better detect vital food sources. Today, it is often assumed that these differences may drive variable food preferences and choices, with downstream effects on health and wellness. A growing body of evidence indicates chemosensory variation is far more complex than previously believed. However, just because a genetic polymorphism results in altered receptor function in cultured cells or even behavioral phenotypes in the laboratory, this variation may not be sufficient to influence food choice in free living humans. Still, there is ample evidence to indicate allelic variation in TAS2R38 predicts variation in bitterness of synthetic pharmaceuticals (e.g., propylthiouracil) and natural plant compounds (e.g., goitrin), and this variation associates with differential intake of alcohol and vegetables. Further, this is only one of 25 unique bitter taste genes (TAS2Rs) in humans, and emerging evidence suggests other TAS2Rs may also contain polymorphisms that a functional with respect to ingestive behavior. For example, TAS2R16 polymorphisms are linked to the bitterness of naturally occurring plant compounds and alcoholic beverage intake, a TAS2R19 polymorphism predicts differences in quinine bitterness and grapefruit bitterness and liking, and TAS2R31 polymorphisms associate with differential bitterness of plant compounds like aristolochic acid and the sulfonyl amide sweeteners saccharin and acesulfame-K. More critically with respect to food choices, these polymorphisms may vary independently from each other within and across individuals, meaning a monolithic one-size-fits-all approach to bitterness needs to be abandoned. Nor are genetic

  3. Association study of ghrelin receptor gene polymorphisms in rheumatoid arthritis.

    PubMed

    Robledo, G; Rueda, B; Gonzalez-Gay, M A; Fernández, B; Lamas, J R; Balsa, A; Pascual-Salcedo, D; García, A; Raya, E; Martín, J

    2010-01-01

    Ghrelin is a newly characterised growth hormone (GH) releasing peptide widely distributed that may play an important role in the regulation of metabolic balance in inflammatory diseases such as rheumatoid arthritis (RA) by decreasing the pro-inflammatory Th1 responses. In this study we investigated the possible contribution of several polymorphisms in the functional Ghrelin receptor to RA susceptibility. A screening of 3 single nucleotide polymorphisms (SNPs) was performed in a total of 950 RA patients and 990 healthy controls of Spanish Caucasian origin. Genotyping of all 3 SNPs was performed by real-time polymerase chain reaction technology, using the TaqMan 5'-allele discrimination assay. We observed no statistically significant deviation between RA patients and controls for the GHSR SNPs analysed. In addition, we performed a haplotype analysis that did not reveal an association with RA susceptibility. The stratification analysis for the presence of shared epitope (SE), rheumatoid factor (RF) or antibodies anti cyclic citrullinated peptide (anti-CCP) did not detect significant association of the GHSR polymorphisms with RA. These findings suggest that the GHSR gene polymorphisms do not appear to play a major role in RA genetic predisposition in our population.

  4. Polymorphism of the renalase gene in gestational diabetes mellitus.

    PubMed

    Fatima, Syeda Sadia; Jamil, Zehra; Alam, Faiza; Malik, Hajira Zafar; Madhani, Sarosh Irfan; Ahmad, Muhammad Saad; Shabbir, Tayyab; Rehmani, Muhammed Noman; Rabbani, Amna

    2017-01-01

    Renalase is considered as a novel candidate gene for type 2 diabetes. In this study, we aimed to investigate the relationship of serum renalase and two single nucleotide polymorphisms with gestational diabetes mellitus. One hundred and ninety-eight normotensive pregnant females (n = 99 gestational diabetes mellitus; n = 99 euglycemic pregnant controls) were classified according to the International Association of the Diabetes and Pregnancy Study criteria. Fasting and 2-h post glucose load blood levels and anthropometric assessment was performed. Serum renalase was measured using enzyme-linked immunosorbent assay, whereas DNA samples were genotyped for renalase single nucleotide polymorphisms rs2576178 and rs10887800 using Polymerase chain reaction-Restriction fragment length polymorphism method. In an age-matched case control study, no difference was observed in the serum levels of renalase (p > 0.05). The variant rs10887800 showed an association with gestational diabetes mellitus and remained significant after multiple adjustments (p < 0.05), whereas rs2576178 showed weak association (p = 0.030) that was lost after multiple adjustments (p = 0.09). We inferred a modest association of the rs10887800 polymorphism with gestational diabetes. Although gestational diabetes mellitus is self-reversible, yet presence of this minor G allele might predispose to metabolic syndrome phenotypes in near the future.

  5. 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

  6. Polymorphisms in inflammation pathway genes and endometrial cancer risk

    PubMed Central

    Delahanty, Ryan J.; Xiang, Yong-Bing; Spurdle, Amanda; Beeghly-Fadiel, Alicia; Long, Jirong; Thompson, Deborah; Tomlinson, Ian; Yu, Herbert; Lambrechts, Diether; Dörk, Thilo; Goodman, Marc T.; Zheng, Ying; Salvesen, Helga B.; Bao, Ping-Ping; Amant, Frederic; Beckmann, Matthias W.; Coenegrachts, Lieve; Coosemans, An; Dubrowinskaja, Natalia; Dunning, Alison; Runnebaum, Ingo B.; Easton, Douglas; Ekici, Arif B.; Fasching, Peter A.; Halle, Mari K.; Hein, Alexander; Howarth, Kimberly; Gorman, Maggie; Kaydarova, Dylyara; Krakstad, Camilla; Lose, Felicity; Lu, Lingeng; Lurie, Galina; O’Mara, Tracy; Matsuno, Rayna K.; Pharoah, Paul; Risch, Harvey; Corssen, Madeleine; Trovik, Jone; Turmanov, Nurzhan; Wen, Wanqing; Lu, Wei; Cai, Qiuyin; Zheng, Wei; Shu, Xiao-Ou

    2013-01-01

    Background Experimental and epidemiological evidence have suggested that chronic inflammation may play a critical role in endometrial carcinogenesis. Methods To investigate this hypothesis, a two-stage study was carried out to evaluate single nucleotide polymorphisms (SNPs) in inflammatory pathway genes in association with endometrial cancer risk. In stage 1, 64 candidate pathway genes were identified and 4,542 directly genotyped or imputed SNPs were analyzed among 832 endometrial cancer cases and 2,049 controls, using data from the Shanghai Endometrial Cancer Genetics Study. Linkage disequilibrium of stage 1 SNPs significantly associated with endometrial cancer (P<0.05) indicated that the majority of associations could be linked to one of 24 distinct loci. One SNP from each of the 24 loci was then selected for follow-up genotyping. Of these, 21 SNPs were successfully designed and genotyped in stage 2, which consisted of ten additional studies including 6,604 endometrial cancer cases and 8,511 controls. Results Five of the 21 SNPs had significant allelic odds ratios and 95% confidence intervals as follows: FABP1, 0.92 (0.85-0.99); CXCL3, 1.16 (1.05-1.29); IL6, 1.08 (1.00-1.17); MSR1, 0.90 (0.82-0.98); and MMP9, 0.91 (0.87-0.97). Two of these polymorphisms were independently significant in the replication sample (rs352038 in CXCL3 and rs3918249 in MMP9). The association for the MMP9 polymorphism remained significant after Bonferroni correction and showed a significant association with endometrial cancer in both Asian- and European-ancestry samples. Conclusions These findings lend support to the hypothesis that genetic polymorphisms in genes involved in the inflammatory pathway may contribute to genetic susceptibility to endometrial cancer. Impact Statement This study adds to the growing evidence that inflammation plays an important role in endometrial carcinogenesis. PMID:23221126

  7. Gene polymorphisms and sport attitude in Italian athletes.

    PubMed

    Sessa, Francesco; Chetta, Massimiliano; Petito, Annamaria; Franzetti, Mauro; Bafunno, Valeria; Pisanelli, Daniela; Sarno, Michelina; Iuso, Salvatore; Margaglione, Maurizio

    2011-04-01

    The aim of this study was to evaluate whether the distribution of polymorphisms in the ACE, ACTN3, NOS3, UCP2, and UCP3 genes, which has been reported to be correlated with different physiological parameters, played a role in sport performance. We focused on a cohort of 82 Italian athletes: first of all, athletes were divided according to type of sport: team (n=72) versus individual (n=10), and subsequently, according to the performance, into "power" sports (n=29; sprinters, short distance swimmers, and volleyball players) and "intermittent" sports (n=53; football, basketball, and hockey players). All the populations studied were in Hardy-Weinberg equilibrium for the following polymorphisms: ACE (I/D), ACTN3 (R577X), NOS3 (-786 T/C), UCP2 (A55V), and UCP3 (-55 C/T). We observed that the frequency of NOS3-786 T and UCP2 C alleles was higher among power athletes compared with controls (p=0.011 and p=0.012, respectively); these alleles were also overrepresented in individual athletes (p=0.02 and p=0.045, respectively), although a small sample was analyzed. The frequency of NOS3 298G allele was higher among power athletes compared with controls (p=0.015); these data remained suggestive after correction for multiple testing. We found a suggestive association between NOS3 (-786 T/C; G298A) and UCP2 (A55V) polymorphisms and power athletes, whereas no significant correlation was found with UCP3 (-55C/T), ACE (I/D), and ACTN3 (R577X) polymorphisms, in contrast to previous studies. Analysis of multiple performance-associated genetic polymorphisms needs further examination to explain the relationship between genetic background and potential success in sport performance.

  8. Polymorphisms in the leptin gene promoter in Brazilian beef herds.

    PubMed

    Guimarães, R C; Azevedo, J S N; Corrêa, S C; Campelo, J E G; Barbosa, E M; Gonçalves, E C; Silva Filho, E

    2016-12-02

    Brazil is the world's largest producer of beef cattle; however, the quality of its herds needs to be improved. The use of molecular markers as auxiliary tools in selecting animals for reproduction with high pattern for beef production would significantly improve the quality of the final beef product in Brazil. The leptin gene has been demonstrated to be an excellent candidate gene for bovine breeding. The objective of this study was to sequence and compare the leptin gene promoter of Brazil's important cattle breeds in order to identify polymorphisms in it. Blood samples of the Nellore, Guzerat, Tabapuã, and Senepol breeds were collected for genomic DNA extraction. The genomic DNA was used as a template for polymerase chain reaction (PCR) to amplify a 1575-bp fragment, which in turn was sequenced, aligned, and compared between animals of different breeds. Twenty-three single nucleotide polymorphic sites, including transitions and transversions, were detected at positions -1457, -1452, -1446, -1397, -1392, -1361, -1238, -963,-901, -578, -516, -483, -478, -470, -432, -430, -292, -282, -272, -211, -202, -170, and -147. Additionally, two insertion sites at positions -680 and -416 and two deletion sites at positions -1255 and -1059 were detected. As the promoter region of the leptin gene has been demonstrated to vary among breeds, these variations must be tested for their use as potential molecular markers for artificial selection of animals for enhanced beef production in different systems of bovine production in Brazil.

  9. Interleukin-6 level and gene polymorphism in spontaneous miscarriage.

    PubMed

    Drozdzik, M; Szlarb, N; Kurzawski, M

    2013-09-01

    The aetiology of spontaneous miscarriage, the most common pregnancy complication, remains undefined. One of postulated factors involved in miscarriage pathology is interleukin 6 (IL-6). Therefore, the aim of the study was to evaluate IL-6 and interleukin 6 receptor (IL-6R) gene polymorphisms in patients with spontaneous miscarriage. One hundred fifty-seven patients diagnosed with spontaneous miscarriage and age and gestational time matched controls were included in the case-control study. In all study participants circulating IL-6 levels (chemiluminescent immunoassay) and IL6-174G>C as well as IL6R rs2228145:A>C polymorphisms were evaluated. The distribution of IL6 as well as IL6R alleles and genotypes were similar in the controls and patients with miscarriage. Only a trend of more frequent appearance of -174GC+CC and C allele in the patients with miscarriage was noted. Blood serum concentrations of IL-6 were significantly elevated in patients with miscarriage vs those with physiological pregnancy. Likewise, IL-6 concentrations differ significantly with the types of miscarriage. The highest concentrations of the cytokine was seen in subjects with incomplete miscarriage (4.28 ± 4.88 pg/ml) followed by imminent miscarriage (2.97 ± 2.42 pg/ml), and then missed miscarriage (2.07 ± 1.90 pg/ml), being significantly the lowest in missed miscarriage group. No association between the IL6 genotype and IL-6 serum concentration were noted, both in the miscarriage group and in the control group. The findings of the study support the role of IL-6 in spontaneous miscarriage irrespectively of its type. However, no correlation between circulating IL-6 and IL6 gene polymorphism, as well as IL-6 and IL-6R polymorphisms associations with spontaneous miscarriage were revealed. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Chemokine gene polymorphisms associate with gender in patients with uveitis.

    PubMed

    Chen, Y; Vaughan, R W; Kondeatis, E; Fortune, F; Graham, E M; Stanford, M R; Wallace, G R

    2004-01-01

    Uveitis is an inflammatory condition of ocular tissue characterized by leukocyte infiltration, tissue damage, and decreased visual acuity. Chemokines have been implicated in the pathogenesis of uveitis. Polymorphisms in the genes encoding chemokines have been described as affecting chemokine production or function. We analyzed the frequency of single-nucleotide polymorphisms (SNPs) in genes encoding CCL2 (-2518 and -2076) and CCL5 (-403 and -28) in patients with Behçet's disease (BD), a systemic form of uveitis, and patients with retinal vasculitis (RV), an organ-specific form of disease. We report that there was no association between any SNP and disease. However, when segregated on the basis of gender the CCR5 -403 AA genotype was only found in male patients with BD. Similarly, CCL2 genotypes 1/2 were predominant in males, while genotype 4 was significantly associated with disease in female patients with BD. Differences in disease symptoms and severity between males and females have been described in BD and gender-specific genetic differences in chemokine gene function may be involved.

  11. RAAS gene polymorphisms influence progression of pediatric hypertrophic cardiomyopathy.

    PubMed

    Kaufman, Beth D; Auerbach, Scott; Reddy, Sushma; Manlhiot, Cedric; Deng, Liyong; Prakash, Ashwin; Printz, Beth F; Gruber, Dorota; Papavassiliou, Dimitrios P; Hsu, Daphne T; Sehnert, Amy J; Chung, Wendy K; Mital, Seema

    2007-12-01

    Hypertrophic Cardiomyopathy (HCM) is a disease with variable rate of progression. Young age is an independent risk factor for poor outcome in HCM. The influence of renin-angiotensin-aldosterone (RAAS) genotype on the progression of HCM in children is unknown. Children with HCM (n = 65) were enrolled prospectively across two centers (2001-2005). All subjects were genotyped for five RAAS gene polymorphisms previously associated with LV hypertrophy (pro-LVH): AGT M235T, ACE DD, CMA-1903 A/G, AGTR1 1666 A/C and CYP11B2-344 C/T. Linear regression models, based on maximum likelihood estimates, were created to assess the independent effect of RAAS genotype on LV hypertrophy (LVH). Forty-six subjects were homozygous for <2 and 19 were homozygous for > or =2 pro-LVH RAAS polymorphisms. Mean age at presentation was 9.6 +/- 6 years. Forty children had follow-up echocardiograms after a median of 1.5 years. Indexed LV mass (LVMI) and LV mass z-scores were higher at presentation and follow-up in subjects with > or =2 pro-LVH genotypes compared to those with <2 (P < 0.05). Subjects with > or =2 pro-LVH genotypes also demonstrated a greater increase in septal thickness (IVST) and in LV outflow tract (LVOT) obstruction on follow-up (P < 0.05). On multivariate analysis, a higher number of pro-LVH genotypes was associated with a larger effect size (P < 0.05). Pro-LVH RAAS gene polymorphisms are associated with progressive septal hypertrophy and LVOT obstruction in children with HCM. Identification of RAAS modifier genes may help to risk-stratify patients with HCM.

  12. Folate and Breast Cancer: Role of Intake, Blood Levels, and Metabolic Gene Polymorphisms

    DTIC Science & Technology

    2005-07-01

    folate, and metabolic gene polymorphisms in relation to breast cancer risk: Months 1-19. b. Prepare blood samples for relevant assays: Months 1-19... gene polymorphism assays among the 184 cases and matched controls. The folate assays are on-going at this time. DNA assays will commence in the... methotrexate . Ann Oncol 13: 1915–1918, 2002 13. Toffoli G, Veronesi A, Boiocchi M, Crivellari D: MTHFR gene polymorphism and severe toxicity during

  13. Fibronectin gene polymorphism in patients with lung cancer.

    PubMed

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

    2001-01-01

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

  14. Origin of the polymorphism of the involucrin gene in Asians.

    PubMed Central

    Djian, P; Delhomme, B; Green, H

    1995-01-01

    The involucrin gene, encoding a protein of the terminally differentiated keratinocyte, is polymorphic in the human. There is polymorphism of marker nucleotides a two positions in the coding region, and there are over eight polymorphic forms based on the number and kind of 10-codon tandem repeats in that part of the coding region most recently added in the human lineage. The involucrin alleles of Caucasians and Africans differ in both nucleotides and repeat patterns. We show that the involucrin alleles of East Asians (Chinese and Japanese) can be divided into two populations according to whether they possess the two marker nucleotides typical of Africans or Caucasians. The Asian population bearing Caucasian-type marker nucleotides has repeat patterns similar to those of Caucasians, whereas Asians bearing African-type marker nucleotides have repeat patterns that resemble those of Africans more than those of Caucasians. The existence of two populations of East Asian involucrin alleles gives support for the existence of a Eurasian stem lineage from which Caucasians and a part of the Asian population originated. PMID:7762559

  15. Granzyme B gene polymorphism associated with subacute sclerosing panencephalitis.

    PubMed

    Yentur, Sibel P; Aydin, Hatice Nur; Gurses, Candan; Demirbilek, Veysi; Kuru, Umit; Uysal, Serap; Yapici, Zuhal; Baris, Safa; Yilmaz, Gülden; Cokar, Ozlem; Onal, Emel; Gokyigit, Ayşen; Saruhan-Direskeneli, Güher

    2014-10-01

     Subacute sclerosing panencephalitis (SSPE) is a late complication of measles infection. Immune dysfunction related to genetic susceptibility has been considered in disease pathogenesis. A functional single nucleotide polymorphism (SNP) of granzyme B gene (GZMB) reported in several pathologies may also be involved in susceptibility to SSPE.  An SNP (rs8192917, G → A, R→Q) was screened in 118 SSPE patients and 221 healthy controls (HC) by polymerase chain reaction-restriction fragment length polymorphism. Frequencies were compared between groups. In vitro production of GZMB was measured in controls with different genotypes.  The SNP had a minor allele (G) frequency of 0.22 in patients and 0.31 in controls. GG genotype was significantly less frequent in patients (odds ratio, 0.23). G allele carriers produced relatively higher levels of GZMB, when stimulated in vitro.  These findings implicate possible effect of this genetic polymorphism in susceptibility to SSPE which needs to be confirmed in bigger populations. Georg Thieme Verlag KG Stuttgart · New York.

  16. The Joint Effects of Body Mass Index and MAOA Gene Polymorphism on Depressive Symptoms.

    PubMed

    Liu, Yangyang

    2015-07-01

    The objective of the present study was to examine the joint effects of the body mass index and the MAOA gene polymorphism on depressive symptoms. In two independent Chinese samples, we measured adolescents' depressive symptoms and body mass index and collected their DNA. The results indicated that the main effects of the MAOA gene polymorphism on depressive symptoms were significant. However, the main effects of body mass index and the interaction of the MAOA gene polymorphism and body mass index on depressive symptoms were not significant. By using Chinese adolescents, this study confirmed that the MAOA gene polymorphism directly influenced adolescents' depressive symptoms.

  17. T cell cytokine gene polymorphisms in canine diabetes mellitus.

    PubMed

    Short, Andrea D; Catchpole, Brian; Kennedy, Lorna J; Barnes, Annette; Lee, Andy C; Jones, Chris A; Fretwell, Neale; Ollier, William E R

    2009-03-15

    Insulin-deficiency diabetes in dogs shares some similarities with human latent autoimmune diabetes of adults (LADA). Canine diabetes is likely to have a complex pathogenesis with multiple genes contributing to overall susceptibility and/or disease progression. An association has previously been shown between canine diabetes and MHC class II genes, although other genes are also likely to contribute to the genetic risk. Potential diabetes susceptibility genes include immuno-regulatory TH1/TH2 cytokines such as IFNgamma, IL-12, IL-4 and IL-10. We screened these candidate genes for single nucleotide polymorphisms (SNPs) in a range of different dog breeds using dHPLC analysis and DNA sequencing. Thirty-eight of the SNPs were genotyped in crossbreed dogs and seven other breed groups (Labrador Retriever, West Highland White Terrier, Collie, Schnauzer, Cairn Terrier, Samoyed and Cavalier King Charles Spaniel), which demonstrated substantial intra-breed differences in allele frequencies. When SNPs were examined for an association with diabetes by case:control analysis significant associations were observed for IL-4 in three breeds, the Collie, Cairn Terrier and Schnauzer and for IL-10 in the Cavalier King Charles Spaniel. These results suggest that canine cytokine genes regulating the TH1/TH2 immune balance might play a contributory role in determining susceptibility to diabetes in some breeds.

  18. Gene-gene, gene-environment, gene-nutrient interactions and single nucleotide polymorphisms of inflammatory cytokines.

    PubMed

    Nadeem, Amina; Mumtaz, Sadaf; Naveed, Abdul Khaliq; Aslam, Muhammad; Siddiqui, Arif; Lodhi, Ghulam Mustafa; Ahmad, Tausif

    2015-05-15

    Inflammation plays a significant role in the etiology of type 2 diabetes mellitus (T2DM). The rise in the pro-inflammatory cytokines is the essential step in glucotoxicity and lipotoxicity induced mitochondrial injury, oxidative stress and beta cell apoptosis in T2DM. Among the recognized markers are interleukin (IL)-6, IL-1, IL-10, IL-18, tissue necrosis factor-alpha (TNF-α), C-reactive protein, resistin, adiponectin, tissue plasminogen activator, fibrinogen and heptoglobins. Diabetes mellitus has firm genetic and very strong environmental influence; exhibiting a polygenic mode of inheritance. Many single nucleotide polymorphisms (SNPs) in various genes including those of pro and anti-inflammatory cytokines have been reported as a risk for T2DM. Not all the SNPs have been confirmed by unifying results in different studies and wide variations have been reported in various ethnic groups. The inter-ethnic variations can be explained by the fact that gene expression may be regulated by gene-gene, gene-environment and gene-nutrient interactions. This review highlights the impact of these interactions on determining the role of single nucleotide polymorphism of IL-6, TNF-α, resistin and adiponectin in pathogenesis of T2DM.

  19. Endometriosis and RAS system gene polymorphisms: the association of ACE A2350G polymorphism with endometriosis in Polish individuals.

    PubMed

    Kowalczyńska, Liliana J; Ferenc, Tomasz; Wojciechowski, Michał; Mordalska, Anna; Pogoda, Krzysztof; Malinowski, Andrzej

    2014-05-01

    To analyze the polymorphisms of angiotensin I converting enzyme (ACE) gene (insertion/deletion [I/D], A2350G) and angiotensin II type 1 receptor gene (A1166C) in women with endometriosis and to determine the correlation of the identified genotypes with the severity of the disease. Additionally, to estimate the prognostic value of the polymorphisms in patients with endometriosis treated due to infertility. The study group included 241 women, the control group (without endometriosis)-127. The molecular analysis was performed by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism technique. For I/D ACE and A1166C AT1 polymorphisms no significant differences were observed between the study and control groups and between the severity grades of the disease (p>0.05). For A2350G ACE polymorphism the frequency of genotypes for the study and control groups respectively was the following: AA-31.54%, AG-54.36%, GG-14.11% and AA-55.12%, AG-36.22%, GG-8.66% (x(2)=19.36, p<0.0001). Statistically significant differences were found between the frequency of A and G alleles between both groups (x(2)=15.16, p=0.0001), but not when individual grades of the disease severity were compared. There was no association between the investigated polymorphisms and the effect of infertility treatment. A2350G polymorphism (allele G, AG genotype) of ACE gene seems to be associated with the development of endometriosis.

  20. Mapping Flagellar Genes in Chlamydomonas Using Restriction Fragment Length Polymorphisms

    PubMed Central

    Ranum, LPW.; Thompson, M. D.; Schloss, J. A.; Lefebvre, P. A.; Silflow, C. D.

    1988-01-01

    To correlate cloned nuclear DNA sequences with previously characterized mutations in Chlamydomonas and, to gain insight into the organization of its nuclear genome, we have begun to map molecular markers using restriction fragment length polymorphisms (RFLPs). A Chlamydomonas reinhardtii strain (CC-29) containing phenotypic markers on nine of the 19 linkage groups was crossed to the interfertile species Chlamydomonas smithii. DNA from each member of 22 randomly selected tetrads was analyzed for the segregation of RFLPs associated with cloned genes detected by hybridization with radioactive DNA probes. The current set of markers allows the detection of linkage to new molecular markers over approximately 54% of the existing genetic map. This study focused on mapping cloned flagellar genes and genes whose transcripts accumulate after deflagellation. Twelve different molecular clones have been assigned to seven linkage groups. The α-1 tubulin gene maps to linkage group III and is linked to the genomic sequence homologous to pcf6-100, a cDNA clone whose corresponding transcript accumulates after deflagellation. The α-2 tubulin gene maps to linkage group IV. The two β-tubulin genes are linked, with the β-1 gene being approximately 12 cM more distal from the centromere than the β-2 gene. A clone corresponding to a 73-kD dynein protein maps to the opposite arm of the same linkage group. The gene corresponding to the cDNA clone pcf6-187, whose mRNA accumulates after deflagellation, maps very close to the tightly linked pf-26 and pf-1 mutations on linkage group V. PMID:2906025

  1. Polymorphisms in endothelin system genes, arsenic levels and obesity risk.

    PubMed

    Martínez-Barquero, Vanesa; de Marco, Griselda; Martínez-Hervas, Sergio; Rentero, Pilar; Galan-Chilet, Inmaculada; Blesa, Sebastian; Morchon, David; Morcillo, Sonsoles; Rojo, Gemma; Ascaso, Juan Francisco; Real, José Tomás; Martín-Escudero, Juan Carlos; Chaves, Felipe Javier

    2015-01-01

    Obesity has been linked to morbidity and mortality through increased risk for many chronic diseases. Endothelin (EDN) system has been related to endothelial function but it can be involved in lipid metabolism regulation: Receptor type A (EDNRA) activates lipolysis in adipocytes, the two endothelin receptors mediate arsenic-stimulated adipocyte dysfunction, and endothelin system can regulate adiposity by modulating adiponectin activity in different situations and, therefore, influence obesity development. The aim of the present study was to analyze if single nucleotide polymorphisms (SNPs) in the EDN system could be associated with human obesity. We analyzed two samples of general-population-based studies from two different regions of Spain: the VALCAR Study, 468 subjects from the area of Valencia, and the Hortega Study, 1502 subjects from the area of Valladolid. Eighteen SNPs throughout five genes were analyzed using SNPlex. We found associations for two polymorphisms of the EDNRB gene which codifies for EDN receptor type B. Genotypes AG and AA of the rs5351 were associated with a lower risk for obesity in the VALCAR sample (p=0.048, OR=0.63) and in the Hortega sample (p=0.001, OR=0.62). Moreover, in the rs3759475 polymorphism, genotypes CT and TT were also associated with lower risk for obesity in the Hortega sample (p=0.0037, OR=0.66) and in the VALCAR sample we found the same tendency (p=0.12, OR=0.70). Furthermore, upon studying the pooled population, we found a stronger association with obesity (p=0.0001, OR=0.61 and p=0.0008, OR=0.66 for rs5351 and rs3759475, respectively). Regarding plasma arsenic levels, we have found a positive association for the two SNPs studied with obesity risk in individuals with higher arsenic levels in plasma: rs5351 (p=0.0054, OR=0.51) and rs3759475 (p=0.009, OR=0.53). Our results support the hypothesis that polymorphisms of the EDNRB gene may influence the susceptibility to obesity and can interact with plasma arsenic levels.

  2. Associations between serotonin-related gene polymorphisms and panic disorder.

    PubMed

    Maron, Eduard; Lang, Aavo; Tasa, Gunnar; Liivlaid, Liivi; Tõru, Innar; Must, Anne; Vasar, Veiko; Shlik, Jakov

    2005-06-01

    Studies suggest that vulnerability to panic attacks and panic disorder (PD) may be related to a deficient serotonin (5-HT) neurotransmission. In the present case-control study we investigated possible associations between PD phenotype and five candidate polymorphisms including 5-HT transporter (5-HTTLPR and VNTR), monoamine oxidase A (MAOA promoter region), tryptophan hydroxylase 1 (TPH1 218A/C) and 5-HT1B receptor (5-HT1BR 861G/C) genes. The study sample consisted of 158 patients with PD and 215 healthy control subjects. The analysis showed higher frequencies of LL genotype (p = 0.016) and L allele variant (p = 0.007) of 5-HTTLPR in the patients. No significant associations were observed between PD and other candidate gene polymorphisms. However, a higher frequency of longer allele genotypes of the MAOA promoter region was observed in female PD patients with agoraphobia than in female controls (p = 0.016). These findings indicate that genetic variants conceivably related to lower 5-HT neurotransmission may be involved in the development of PD.

  3. Environmental Adaptation Contributes to Gene Polymorphism across the Arabidopsis thaliana Genome

    PubMed Central

    Lee, Cheng-Ruei

    2012-01-01

    The level of within-species polymorphism differs greatly among genes in a genome. Many genomic studies have investigated the relationship between gene polymorphism and factors such as recombination rate or expression pattern. However, the polymorphism of a gene is affected not only by its physical properties or functional constraints but also by natural selection on organisms in their environments. Specifically, if functionally divergent alleles enable adaptation to different environments, locus-specific polymorphism may be maintained by spatially heterogeneous natural selection. To test this hypothesis and estimate the extent to which environmental selection shapes the pattern of genome-wide polymorphism, we define the "environmental relevance" of a gene as the proportion of genetic variation explained by environmental factors, after controlling for population structure. We found substantial effects of environmental relevance on patterns of polymorphism among genes. In addition, the correlation between environmental relevance and gene polymorphism is positive, consistent with the expectation that balancing selection among heterogeneous environments maintains genetic variation at ecologically important genes. Comparison of the gene ontology annotations shows that genes with high environmental relevance are enriched in unknown function categories. These results suggest an important role for environmental factors in shaping genome-wide patterns of polymorphism and indicate another direction of genomic study. PMID:22798389

  4. Impact of estrogen receptor α gene and oxytocin receptor gene polymorphisms on female sexuality

    PubMed Central

    Armeni, Anastasia K; Assimakopoulos, Konstantinos; Marioli, Dimitra; Koika, Vassiliki; Michaelidou, Euthychia; Mourtzi, Niki; Iconomou, Gregoris

    2017-01-01

    Over the past decades, research attention has increasingly been paid to the neurobiological component of sexual behavior. The aim of the present study was to investigate the correlation of estrogen receptor α (ERA) gene polymorphism (rs2234693-PvuII) (T→C substitution) and oxytocin receptor gene polymorphism (rs53576) (G→A substitution) with sexuality parameters of young, healthy women. One hundred thirty-three Greek heterosexual women, students in higher education institutions, 20–25 years of age, sexually active, with normal menstrual cycles (28–35 days), were recruited in the study. Exclusion criteria were chronic and/or major psychiatric diseases, use of oral contraceptive pills (OCs), polycystic ovary syndrome (PCOS), thyroid diseases as well as drugs that are implicated in hypothalamus–pituitary–gonadal axis. T allele (wildtype) of rs2234693 (PvuII) polymorphism of ERA gene was correlated with increased levels of arousal and lubrication, whereas A allele (polymorphic) of rs53576 (OXTR) polymorphism was correlated with increased arousal levels. The simultaneous presence of both T allele of rs2234693 (PvuII) and A allele of rs53576 (OXTR) polymorphisms (T + A group) was correlated with increased arousal, orgasm levels as well as female sexual function index full score. To our knowledge, this is the first study to investigate the interaction between ERA and OXTR with regard to sexual function in women. Female sexuality is a complex behavioral trait that encompasses both biological and psychological components. It seems that variability in female sexual response stems from genetic variability that characterizes endocrine, neurotransmitter and central nervous system influences. PMID:28069897

  5. Gene polymorphisms and increased DNA damage in morbidly obese women.

    PubMed

    Luperini, B C O; Almeida, D C; Porto, M P; Marcondes, J P C; Prado, R P; Rasera, I; Oliveira, M R M; Salvadori, D M F

    2015-06-01

    Obesity is characterized by increased adipose tissue mass resulting from a chronic imbalance between energy intake and expenditure. Furthermore, there is a clearly defined relationship among fat mass expansion, chronic low-grade systemic inflammation and reactive oxygen species (ROS) generation; leading to ROS-related pathological events. In the past years, genome-wide association studies have generated convincing evidence associating genetic variation at multiple regions of the genome with traits that reflect obesity. Therefore, the present study aimed to evaluate the relationships among the gene polymorphisms ghrelin (GHRL-rs26802), ghrelin receptor (GHSR-rs572169), leptin (LEP-rs7799039), leptin receptor (LEPR-rs1137101) and fat mass and obesity-associated (FTO-rs9939609) and obesity. The relationships among these gene variants and the amount of DNA damage were also investigated. Three hundred Caucasian morbidly obese and 300 eutrophic (controls) women were recruited. In summary, the results demonstrated that the frequencies of the GHRL, GHSR, LEP and LEPR polymorphisms were not different between Brazilian white morbidly obese and eutrophic women. Exceptions were the AA-FTO genotype and allele A, which were significantly more frequent in obese women than in the controls (0.23% vs. 0.10%; 0.46 vs. 0.36, respectively), and the TT-FTO genotype and the T allele, which were less frequent in morbidly obese women (p<0.01). Furthermore, significant differences in the amount of genetic lesions associated with FTO variants were observed only in obese women. In conclusion, this study demonstrated that the analyzed SNPs were not closely associated with morbid obesity, suggesting they are not the major contributors to obesity. Therefore, our data indicated that these gene variants are not good biomarkers for predicting risk susceptibility for obesity, whereas ROS generated by the inflammatory status might be one of the causes of DNA damage in obese women, favoring

  6. Apolipoprotein gene polymorphisms as cause of cholesterol QTLs in mice.

    PubMed

    Suto, Jun-ichi

    2005-06-01

    Quantitative trait locus (QTL) analyses of plasma cholesterol levels were carried out in three sets of F(2) mice that were formed in a 'round-robin' manner from C57BL/6J, KK (-A(y)), and RR strains. Six QTLs were identified on chromosomes 1 (Cq1, Cq2, and Cq6), 3 (Cq3), and 9 (Cq4 and Cq5); of these, Cq2 colocalized with Cq6, and Cq4 colocalized with Cq5. The major candidate gene for Cq2 and Cq6 is Apoa2, and that for Cq4 and Cq5 is Apoa4. The adequacy of polymorphisms in candidate genes as cause of QTLs was investigated in this study. For Apoa2, three different alleles (Apoa2(a), Apoa2(b), and Apoa2(c)) are known. Since there was no significant physiologic difference between Apoa2(a) and Apoa2(c) alleles, previous hypothesis that Apoa2(b) was different from Apoa2(a) and Apoa2(c) in the ability to increase cholesterol levels was further supported. Presumably, G-to-A substitution at nucleotide 84 and/or C-to-T substitution at nucleotide 182 are crucial to make the Apoa2(b) unique. On the other hand, for Apoa4, the most striking polymorphism was the number of Glu-Gln-Ala/Val-Gln repeats in carboxyl end; however, this might not be responsible for QTLs. Instead, a silent mutation, C-to-T substitution at nucleotide 771, was shown to be completely correlated with the occurrence of QTLs in a total of six F(2) intercrosses. Provisionally, but reasonably, these base substitutions are qualified as primary causes that constitute QTL effect. The potential strategy for identifying genes and base substitutions underlying QTLs is discussed.

  7. Plasmodium vivax multidrug resistance-1 gene polymorphism in French Guiana.

    PubMed

    Faway, Emilie; Musset, Lise; Pelleau, Stéphane; Volney, Béatrice; Casteras, Jessica; Caro, Valérie; Menard, Didier; Briolant, Sébastien; Legrand, Eric

    2016-11-08

    Plasmodium vivax malaria is a major public health problem in French Guiana. Some cases of resistance to chloroquine, the first-line treatment used against P. vivax malaria, have been described in the Brazilian Amazon region. The aim of this study is to investigate a possible dispersion of chloroquine-resistant P. vivax isolates in French Guiana. The genotype, polymorphism and copy number variation, of the P. vivax multidrug resistance gene-1 (pvmdr1) have been previously associated with modification of the susceptibility to chloroquine. The pvmdr1 gene polymorphism was evaluated by sequencing and copy number variation was assessed by real-time PCR, in P. vivax isolates obtained from 591 symptomatic patients from 1997 to 2013. The results reveal that 1.0% [95% CI 0.4-2.2] of French Guiana isolates carry the mutations Y976F and F1076L, and that the proportion of isolates with multiple copies of pvmdr1 has significantly decreased over time, from 71.3% (OR = 6.2 [95% CI 62.9-78.7], p < 0.0001) in 1997-2004 to 12.8% (OR = 0.03 [95% CI 9.4-16.9], p < 0.0001) in 2009-2013. A statistically significant relationship was found between Guf-A (harboring the single mutation T958M) and Sal-1 (wild type) alleles and pvmdr1 copy number. Few P. vivax isolates harboring chloroquine-resistant mutations in the pvmdr1 gene are circulating in French Guiana. However, the decrease in the prevalence of isolates carrying multiple copies of pvmdr1 might indicate that the P. vivax population in French Guiana is evolving towards a decreased susceptibility to chloroquine.

  8. [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.

  9. Gene Expression and Polymorphism of Myostatin Gene and its Association with Growth Traits in Chicken.

    PubMed

    Dushyanth, K; Bhattacharya, T K; Shukla, R; Chatterjee, R N; Sitaramamma, T; Paswan, C; Guru Vishnu, P

    2016-10-01

    Myostatin is a member of TGF-β super family and is directly involved in regulation of body growth through limiting muscular growth. A study was carried out in three chicken lines to identify the polymorphism in the coding region of the myostatin gene through SSCP and DNA sequencing. A total of 12 haplotypes were observed in myostatin coding region of chicken. Significant associations between haplogroups with body weight at day 1, 14, 28, and 42 days, and carcass traits at 42 days were observed across the lines. It is concluded that the coding region of myostatin gene was polymorphic, with varied levels of expression among lines and had significant effects on growth traits. The expression of MSTN gene varied during embryonic and post hatch development stage.

  10. Canine candidate genes for dilated cardiomyopathy: annotation of and polymorphic markers for 14 genes.

    PubMed

    Wiersma, Anje C; Leegwater, Peter Aj; van Oost, Bernard A; Ollier, William E; Dukes-McEwan, Joanna

    2007-10-19

    Dilated cardiomyopathy is a myocardial disease occurring in humans and domestic animals and is characterized by dilatation of the left ventricle, reduced systolic function and increased sphericity of the left ventricle. Dilated cardiomyopathy has been observed in several, mostly large and giant, dog breeds, such as the Dobermann and the Great Dane. A number of genes have been identified, which are associated with dilated cardiomyopathy in the human, mouse and hamster. These genes mainly encode structural proteins of the cardiac myocyte. We present the annotation of, and marker development for, 14 of these genes of the dog genome, i.e. alpha-cardiac actin, caveolin 1, cysteine-rich protein 3, desmin, lamin A/C, LIM-domain binding factor 3, myosin heavy polypeptide 7, phospholamban, sarcoglycan delta, titin cap, alpha-tropomyosin, troponin I, troponin T and vinculin. A total of 33 Single Nucleotide Polymorphisms were identified for these canine genes and 11 polymorphic microsatellite repeats were developed. The presented polymorphisms provide a tool to investigate the role of the corresponding genes in canine Dilated Cardiomyopathy by linkage analysis or association studies.

  11. Canine candidate genes for dilated cardiomyopathy: annotation of and polymorphic markers for 14 genes

    PubMed Central

    Wiersma, Anje C; Leegwater, Peter AJ; van Oost, Bernard A; Ollier, William E; Dukes-McEwan, Joanna

    2007-01-01

    Background Dilated cardiomyopathy is a myocardial disease occurring in humans and domestic animals and is characterized by dilatation of the left ventricle, reduced systolic function and increased sphericity of the left ventricle. Dilated cardiomyopathy has been observed in several, mostly large and giant, dog breeds, such as the Dobermann and the Great Dane. A number of genes have been identified, which are associated with dilated cardiomyopathy in the human, mouse and hamster. These genes mainly encode structural proteins of the cardiac myocyte. Results We present the annotation of, and marker development for, 14 of these genes of the dog genome, i.e. α-cardiac actin, caveolin 1, cysteine-rich protein 3, desmin, lamin A/C, LIM-domain binding factor 3, myosin heavy polypeptide 7, phospholamban, sarcoglycan δ, titin cap, α-tropomyosin, troponin I, troponin T and vinculin. A total of 33 Single Nucleotide Polymorphisms were identified for these canine genes and 11 polymorphic microsatellite repeats were developed. Conclusion The presented polymorphisms provide a tool to investigate the role of the corresponding genes in canine Dilated Cardiomyopathy by linkage analysis or association studies. PMID:17949487

  12. Serum amyloid A1: Structure, function and gene polymorphism

    PubMed Central

    Sun, Lei; Ye, Richard D.

    2017-01-01

    Inducible expression of serum amyloid A (SAA) is a hallmark of the acute-phase response, which is a conserved reaction of vertebrates to environmental challenges such as tissue injury, infection and surgery. Human SAA1 is encoded by one of the four SAA genes and is the best-characterized SAA protein. Initially known as a major precursor of amyloid A (AA), SAA1 has been found to play an important role in lipid metabolism and contributes to bacterial clearance, the regulation of inflammation and tumor pathogenesis. SAA1 has five polymorphic coding alleles (SAA1.1 – SAA1.5) that encode distinct proteins with minor amino acid substitutions. Single nucleotide polymorphism (SNP) has been identified in both the coding and non-coding regions of human SAA1. Despite high levels of sequence homology among these variants, SAA1 polymorphisms have been reported as risk factors of cardiovascular diseases and several types of cancer. A recently solved crystal structure of SAA1.1 reveals a hexameric bundle with each of the SAA1 subunits assuming a 4-helix structure stabilized by the C-terminal tail. Analysis of the native SAA1.1 structure has led to the identification of a competing site for high-density lipoprotein (HDL) and heparin, thus providing the structural basis for a role of heparin and heparan sulfate in the conversion of SAA1 to AA. In this brief review, we compares human SAA1 with other forms of human and mouse SAAs, and discuss how structural and genetic studies of SAA1 have advanced our understanding of the physiological functions of the SAA proteins. PMID:26945629

  13. Detoxification genes polymorphisms in SIDS exposed to tobacco smoke.

    PubMed

    Filonzi, Laura; Magnani, Cinzia; Lavezzi, Anna Maria; Vaghi, Marina; Nosetti, Luana; Nonnis Marzano, Francesco

    2018-03-30

    The best hypothesis to explain Sudden Infant Death Syndrome (SIDS) pathogenesis is offered by the "triple risk model", which suggests that an interaction of different variables related to exogenous stressors and infant vulnerability may lead to the syndrome. Environmental factors are triggers that act during a particular sensible period, modulated by intrinsic genetic characteristics. Although literature data show that one of the major SIDS risk factors is smoking exposure, a specific involvement of molecular components has never been highlighted. Starting from these observations and considering the role of GSTT1 and GSTM1 genes functional polymorphisms in the detoxification process, we analyzed GSTM1 and GSTT1 null genotype frequencies in 47 SIDS exposed to tobacco smoke and 75 healthy individuals. A significant association (p < .0001) between the GSTM1 null genotype and SIDS exposed to smoke was found. On the contrary, no association between GSTT1 polymorphism and SIDS was determined. Results indicated the contribution of the GSTM1 -/- genotype resulting in null detoxification activity in SIDS cases, and led to a better comprehension of the triple risk model, highlighting smoking exposure as a real SIDS risk factor on a biochemical basis. Copyright © 2018. Published by Elsevier B.V.

  14. Polymorphism of prion protein gene in Arctic fox (Vulpes lagopus).

    PubMed

    Wan, Jiayu; Bai, Xue; Liu, Wensen; Xu, Jing; Xu, Ming; Gao, Hongwei

    2009-07-01

    Prion diseases are fatal neurodegenerative disorders of humans and certain other mammals. Prion protein gene (Prnp) is associated with susceptibility and species barrier to prion diseases. No natural and experimental prion diseases have been documented to date in Arctic fox. In the present study, coding region of Prnp from 135 Arctic foxes were cloned and screened for polymorphisms. Our results indicated that the Arctic fox Prnp open reading frame (ORF) contains 771 nucleotides encoding 257 amino acids. Four single nucleotide polymorphisms (SNPs) (G312C, A337G, C541T, and A723G) were identified. SNPs G312C and A723G produced silent mutations, but SNPs A337G and C541T resulted in a M-V change at codon 113 and R-C at codon 181, respectively. The Arctic fox Prnp amino acid sequence was similar to that of the dog (XM 542906). In short, this study provides preliminary information about genotypes of Prnp in Arctic fox.

  15. Selection with Gene-Cytoplasm Interactions. I. Maintenance of Cytoplasm Polymorphisms

    PubMed Central

    Gregorius, H. R.; Ross, M. D.

    1984-01-01

    General conditions for the protectedness of gene-cytoplasm polymorphisms are considered for a biallelic model with two cytoplasm types and under the assumption that nuclear polymorphisms cannot be maintained in the presence of only one cytoplasm type. Analytical results involving male fertilities, female fertilities, viabilities and selfing rates are obtained, and numerical results show spiral and cyclic behavior of population trajectories. It is shown that a maternally inherited cytoplasmic polymorphism cannot be maintained in the absence of a nuclear polymorphism, and that a gene-cytoplasm polymorphism can only be maintained if the population shows sexual asymmetry, i.e. , if the ratio of male to female fertility varies among genotypes. Thus, the classical viability selection model does not allow gene-cytoplasm polymorphisms. PMID:17246213

  16. A variety of gene polymorphisms associated with idiopathic granulomatous mastitis

    PubMed Central

    Destek, Sebahattin; Gul, Vahit Onur; Ahioglu, Serkan

    2016-01-01

    Idiopathic granulomatous mastitis (IGM) is a rare and chronic inflammatory disorder. IGM mimics breast cancer regarding its clinical and radiological features. Etiology of IGM remains unclarified. Our patient was 37-year-old and 14 weeks pregnant. There was pain, redness and swelling in the right breast. The mass suggestive of malignancy was detected in sonography. Serum CA 125 and CA 15-3 levels were high. Genetic analysis was performed for the etiology. methylenetetrahydrofolate reductase (MTHFR) C 677 TT, β-fibrinogen-455 G>A, plasminogen activator inhibitor (PAI)-1 5 G/5 G, angiotensin-converting enzyme (ACE) I/D mutation was found. IGM was diagnosed by cor biopsy. An association was also reported between breast cancer and mutations in MTHFR-C 677 T, PAI-1, ACE genes. Genetic polymorphisms may involve in the development of IGM as it was seen in our case. Further studies should be conducted to better clarify this plausible association. PMID:27619324

  17. AMPD1 gene polymorphism and the vasodilatory response to ischemia.

    PubMed

    Hand, Brian D; Roth, Stephen M; Roltsch, Mark H; Park, Jung-Jun; Kostek, Matthew C; Ferrell, Robert E; Brown, Michael D

    2006-09-05

    Peripheral vasculature resistance can play an important role in affecting blood pressure and the development of cardiovascular disease. A better understanding of the genes that encode vasodilators, such as adenosine, will provide insight into the mechanisms underlying cardiovascular disease. We tested whether the adenosine monophosphate deaminase-1 (AMPD1) C34T gene polymorphism was associated with the vasodilatory response to ischemia in Caucasian females aged 18-35 years. Blood samples (n = 58) were analyzed for the C34T variant and resulted in the following genotype groups: CC (n = 45) and CT (n = 13). Mean blood pressure (MBP), heart rate, and forearm blood flow (FBF) measured by venous occlusion plethysmography were measured at baseline and at 1 (peak FBF), 2 and 3 min of vasodilation during reactive hyperemia following 5 min of arm ischemia. To control for interindividual variability in baseline FBF and forearm vascular resistance (FVR) the percent change in FBF and FVR were calculated for each min. The percent decrease in FVR was significantly greater in the CT compared to the CC genotype group (-40+/-4% vs. -24+/-3%, P = 0.01) during the 2nd min of reactive hyperemia. The percent increase in FBF tended to be greater in the CT compared to the CC genotype group (+69+/-9% vs. +42+/-9%, P = 0.07) during the 2nd min of reactive hyperemia after adjustment for percent body fat. Consistent with previous findings of increased production of adenosine during exercise in individuals carrying a T allele, our findings suggest that the AMPD1 C34T polymorphism is associated with vasodilatory response to ischemia in the peripheral vasculature because individuals with the T allele had a greater vasodilatory response to ischemia.

  18. Interleukin 18 receptor 1 gene polymorphisms are associated with asthma.

    PubMed

    Zhu, Guohua; Whyte, Moira K B; Vestbo, Jorgen; Carlsen, Karin; Carlsen, Kai-Håkon; Lenney, Warren; Silverman, Michael; Helms, Peter; Pillai, Sreekumar G

    2008-09-01

    The interleukin 18 receptor (IL18R1) gene is a strong candidate gene for asthma. It has been implicated in the pathophysiology of asthma and maps to an asthma susceptibility locus on chromosome 2q12. The possibility of association between polymorphisms in IL18R1 and asthma was examined by genotyping seven SNPs in 294, 342 and 100 families from Denmark, United Kingdom and Norway and conducting family-based association analyses for asthma, atopic asthma and bronchial hyper-reactivity (BHR) phenotypes. Three SNPs in IL18R1 were associated with asthma (0.01131 < or = P < or = 0.01377), five with atopic asthma (0.00066 < or = P < or = 0.00405) and two with BHR (0.01450 < or = P < or = 0.03203) in the Danish population; two SNPs were associated with atopic asthma (0.00397 < or = P < or = 0.01481) and four with BHR (0.00435 < or = P < or = 0.03544) in the UK population; four SNPs showed associations with asthma (0.00015 < or = P < or = 0.03062), two with atopic asthma (0.01269 < or = P < or = 0.04042) and three with BHR (0.00259 < or = P < or = 0.01401) in the Norwegian population; five SNPs showed associations with asthma (0.00005 < or = P < or = 0.03744), five with atopic asthma (0.00001 < or = P < or = 0.04491) and three with BHR (0.03568 < or = P < or = 0.04778) in the combined population. Three intronic SNPs (rs1420099, rs1362348 and rs1974675) showed replicated association for at least one asthma-related phenotype. These results demonstrate significant association between polymorphisms in IL18R1 and asthma.

  19. The role of IL-16 gene polymorphisms in endometriosis

    PubMed Central

    Eliopoulos, Elias; Matalliotaki, Charoula; Rahmioglu, Nilufer; Kalogiannidis, Ioannis; Zondervan, Krina; Spandidos, Demetrios A.; Matalliotakis, Ioannis

    2018-01-01

    Endometriosis is one of the most common gynecological diseases affecting up to 10% of the female population of childbearing age and a major cause of pain and infertility. It is influenced by multiple genetic, epigenetic and environmental factors. Interleukin-16 (IL-16) is a proinflammatory cytokine playing a pivotal role in many inflammatory and autoimmune diseases as well as in the pathogenesis of endometriosis. The aim of the present study was to evaluate the association of two IL-16 gene single nucleotide polymorphisms (SNPs), rs4072111 and rs11556218, with the risk of endometriosis in women from Greece as well as to gain insight about the structural consequences of these two exonic SNPs regarding development of the disease. A total of 159 women with endometriosis (stages I–IV) hospitalized for endometriosis, diagnosed by laparoscopic intervention and histologically confirmed, and 146 normal controls were recruited and genotyped. Subjects were genotyped using a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) strategy. A significant association was detected regarding the GG and GT genotype as well as 'G' allele of rs11556218 in patients with endometriosis. The rs4072111 SNP of the IL-16 gene was not found to be associated with an increased susceptibility to endometriosis either for all patients (stages I–IV) or for stage III and IV of the disease only. Our results demonstrated that rs11556218 is associated with endometriosis in Greek women, probably by resulting in the aberrant expression of IL-16, as suggested by the bioinformatics analysis conducted on the SNP-derived protein sequences, which indicated a possible association between mutation and functional modification of Pro-IL-16. PMID:29328375

  20. Cloning and polymorphisms of yak lactate dehydrogenase B gene.

    PubMed

    Wang, Guosheng; Zhao, Xingbo; Zhong, Juming; Cao, Meng; He, Qinghua; Liu, Zhengxin; Lin, Yaqiu; Xu, Yaou; Zheng, Yucai

    2013-06-05

    The main objective of this work was to study the unique polymorphisms of the lactate dehydrogenase-1 (LDH1) gene in yak (Bos grunniens). Native polyacrylamide gel electrophoresis revealed three phenotypes of LDH1 (a tetramer of H subunit) in yak heart and longissimus muscle extracts. The corresponding gene, ldhb, encoding H subunits of three LDH1 phenotypes was obtained by RT-PCR. A total of six nucleotide differences were detected in yak ldhb compared with that of cattle, of which five mutations cause amino acid substitutions. Sequence analysis shows that the G896A and C689A, mutations of ldhb gene, result in alterations of differently charged amino acids, and create the three phenotypes (F, M, and S) of yak LDH1. Molecular modeling of the H subunit of LDH indicates that the substituted amino acids are not located within NAD+ or substrate binding sites. PCR-RFLP examination of G896A mutation demonstrated that most LDH1-F samples are actually heterozygote at this site. These results help to elucidate the molecular basis and genetic characteristic of the three unique LDH1 phenotypes in yak.

  1. Cloning and Polymorphisms of Yak Lactate Dehydrogenase b Gene

    PubMed Central

    Wang, Guosheng; Zhao, Xingbo; Zhong, Juming; Cao, Meng; He, Qinghua; Liu, Zhengxin; Lin, Yaqiu; Xu, Yaou; Zheng, Yucai

    2013-01-01

    The main objective of this work was to study the unique polymorphisms of the lactate dehydrogenase-1 (LDH1) gene in yak (Bos grunniens). Native polyacrylamide gel electrophoresis revealed three phenotypes of LDH1 (a tetramer of H subunit) in yak heart and longissimus muscle extracts. The corresponding gene, ldhb, encoding H subunits of three LDH1 phenotypes was obtained by RT-PCR. A total of six nucleotide differences were detected in yak ldhb compared with that of cattle, of which five mutations cause amino acid substitutions. Sequence analysis shows that the G896A and C689A, mutations of ldhb gene, result in alterations of differently charged amino acids, and create the three phenotypes (F, M, and S) of yak LDH1. Molecular modeling of the H subunit of LDH indicates that the substituted amino acids are not located within NAD+ or substrate binding sites. PCR-RFLP examination of G896A mutation demonstrated that most LDH1-F samples are actually heterozygote at this site. These results help to elucidate the molecular basis and genetic characteristic of the three unique LDH1 phenotypes in yak. PMID:23739677

  2. Leptin gene and leptin receptor gene polymorphisms are associated with sweet preference and obesity.

    PubMed

    Mizuta, Einosuke; Kokubo, Yoshihiro; Yamanaka, Itaru; Miyamoto, Yoshihiro; Okayama, Akira; Yoshimasa, Yasunao; Tomoike, Hitonobu; Morisaki, Hiroko; Morisaki, Takayuki

    2008-06-01

    Leptin is an adipocyte-secreted hormone that regulates food intake and body weight, and that was recently reported to suppress sweet sensitivity in an animal model. We investigated the associations among sweet preference, obesity, and polymorphisms of the leptin gene (LEP) or leptin receptor gene (LEPR). A total of 3,653 residents randomly selected from among the citizens of Suita City, Osaka, Japan were enlisted as subjects, in whom we investigated sweet preference, clinical characteristics, including obesity and serum leptin level, and the polymorphisms of LEP and LEPR (G-2548A and A19G for LEP; R109K, R223Q, and rs3790439 for LEPR). We determined the associations among the parameters using logistic regression analysis, in order to consider potential confounding factors for sweet preference and/or obesity. The LEP A19G and LEPR R109K polymorphisms were associated with sweet preference, whereas the serum leptin level was not. Further, the LEPR 109KK genotype was found to be associated with obesity along with sweet preference. In conclusion, our results are the first to show associations of LEP and LEPR polymorphisms with sweet preference, and may provide useful information for diagnosis and treatment of lifestyle-related diseases.

  3. Association of interleukins genes polymorphisms with multi-drug resistant tuberculosis in Ukrainian population.

    PubMed

    Butov, Dmytro O; Kuzhko, Mykhaylo M; Makeeva, Natalia I; Butova, Tetyana S; Stepanenko, Hanna L; Dudnyk, Andrii B

    2016-01-01

    Multi-drug resistant tuberculosis (MDR TB) is a significant health problem in some parts of the world. Three major cytokines involved in TB immunopathogenesis include IL-2, IL-4 and IL-10. The susceptibility to MDR TB may be genetically determined. The aim of the study was to assess the association of IL-2, IL-4, IL-10 gene polymorphisms with multi-drug resistant tuberculosis (MDR TB) in Ukrainian population. We observed 140 patients suffering from infiltrative pulmonary tuberculosis (PT) and 30 apparently healthy subjects. The patients were assigned to two groups whether they suffer or do not suffer from pulmonary MDR TB. Interleukin gene (IL) polymorphisms, particularly T330G polymorphism in the IL-2 gene, C589T polymorphism in the IL-4 gene and G1082A polymorphism in the IL-10 gene were studied through polymerase chain reaction. Circulating levels of IL-2, IL-4 and IL-10 in venous blood were estimated using ELISA. Prior to treatment, patients with PT showed significant increase of IL-2 levels and decrease of IL-4 and IL-10 levels compared to apparently healthy subjects. Circulating IL-4 and IL-10 levels were significantly decreased whilst serum IL-2 level was significantly increased in patients with MDR TB compared to non-MDR TB. Low IL-4 and IL-10 secretion and considerable IL-2 alterations were shown to be significantly associated with mutations of homozygous and heterozygous genotypes affecting C589T polymorphism in the IL-4 gene, G1082A polymorphism in the IL-10 gene and T330G polymorphism in the IL-2 gene in patients with PT. Heterozygous genotype and mutations homozygous genotypes gene in polymorphisms determining specified cytokines' production is a PT risk factor and may lead to disease progression into chronic phase. Heterozygous genotype of aforementioned cytokine genetic polymorphisms was significantly the most frequent in patients with MDR TB.

  4. Gene network polymorphism is the raw material of natural selection: the selfish gene network hypothesis.

    PubMed

    Boldogköi, Zsolt

    2004-09-01

    Population genetics, the mathematical theory of modern evolutionary biology, defines evolution as the alteration of the frequency of distinct gene variants (alleles) differing in fitness over the time. The major problem with this view is that in gene and protein sequences we can find little evidence concerning the molecular basis of phenotypic variance, especially those that would confer adaptive benefit to the bearers. Some novel data, however, suggest that a large amount of genetic variation exists in the regulatory region of genes within populations. In addition, comparison of homologous DNA sequences of various species shows that evolution appears to depend more strongly on gene expression than on the genes themselves. Furthermore, it has been demonstrated in several systems that genes form functional networks, whose products exhibit interrelated expression profiles. Finally, it has been found that regulatory circuits of development behave as evolutionary units. These data demonstrate that our view of evolution calls for a new synthesis. In this article I propose a novel concept, termed the selfish gene network hypothesis, which is based on an overall consideration of the above findings. The major statements of this hypothesis are as follows. (1) Instead of individual genes, gene networks (GNs) are responsible for the determination of traits and behaviors. (2) The primary source of microevolution is the intraspecific polymorphism in GNs and not the allelic variation in either the coding or the regulatory sequences of individual genes. (3) GN polymorphism is generated by the variation in the regulatory regions of the component genes and not by the variance in their coding sequences. (4) Evolution proceeds through continuous restructuring of the composition of GNs rather than fixing of specific alleles or GN variants.

  5. New polymorphisms of Xeroderma Pigmentosum DNA repair genes in myelodysplastic syndrome.

    PubMed

    Santiago, Sabrina Pinheiro; Junior, Howard Lopes Ribeiro; de Sousa, Juliana Cordeiro; de Paula Borges, Daniela; de Oliveira, Roberta Taiane Germano; Farias, Izabelle Rocha; Costa, Marília Braga; Maia, Allan Rodrigo Soares; da Nóbrega Ito, Mayumi; Magalhães, Silvia Maria Meira; Pinheiro, Ronald Feitosa

    2017-07-01

    The association between Xeroderma Pigmentosum DNA repair genes (XPA rs1800975, XPC rs2228000, XPD rs1799793 and XPF rs1800067) polymorphisms and myelodysplastic syndrome (MDS) have not been reported. To assess the functional role between these polymorphisms and MDS, we evaluated 189 samples stratified in two groups: 95 bone marrow samples from MDS patients and 94 from healthy elderly volunteers used as controls. Genotypes for all polymorphisms were identified in DNA samples in an allelic discrimination experiment by real-time polymerase chain reaction (qPCR). We also studied the mRNA expression of XPA and XPC genes to evaluate if its polymorphisms were functional in 53 RNAm MDS patients by qPCR methodologies. To the rs2228000 polymorphism, the CT and TT polymorphic genotype were associated with increased odds ratio (OR) of more profound cytopenia (hemoglobin and neutrophils count). To the rs1799793 polymorphism, we found that the GG homozygous wild-type genotype was associated with a decreased chance of developing MDS. We observed low expression of XPA in younger patients, in hypoplastic MDS and patients with abnormal karyotype when presented AG or AA polymorphic genotypes. We also found that there was a statistically significant interaction between the presence of micromegakaryocyte on down regulation of XPC regarding the CT heterozygous genotype of the rs1800975 polymorphism. Our results suggest that new functional polymorphisms of Xeroderma Pigmentosum DNA repair genes in MDS are related to its pathogenesis and prognosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Gene Presence-Absence Polymorphism in Castrating Anther-Smut Fungi: Recent Gene Gains and Phylogeographic Structure.

    PubMed

    Hartmann, Fanny E; Rodríguez de la Vega, Ricardo C; Brandenburg, Jean-Tristan; Carpentier, Fantin; Giraud, Tatiana

    2018-04-01

    Gene presence-absence polymorphisms segregating within species are a significant source of genetic variation but have been little investigated to date in natural populations. In plant pathogens, the gain or loss of genes encoding proteins interacting directly with the host, such as secreted proteins, probably plays an important role in coevolution and local adaptation. We investigated gene presence-absence polymorphism in populations of two closely related species of castrating anther-smut fungi, Microbotryum lychnidis-dioicae (MvSl) and M. silenes-dioicae (MvSd), from across Europe, on the basis of Illumina genome sequencing data and high-quality genome references. We observed presence-absence polymorphism for 186 autosomal genes (2% of all genes) in MvSl, and only 51 autosomal genes in MvSd. Distinct genes displayed presence-absence polymorphism in the two species. Genes displaying presence-absence polymorphism were frequently located in subtelomeric and centromeric regions and close to repetitive elements, and comparison with outgroups indicated that most were present in a single species, being recently acquired through duplications in multiple-gene families. Gene presence-absence polymorphism in MvSl showed a phylogeographic structure corresponding to clusters detected based on SNPs. In addition, gene absence alleles were rare within species and skewed toward low-frequency variants. These findings are consistent with a deleterious or neutral effect for most gene presence-absence polymorphism. Some of the observed gene loss and gain events may however be adaptive, as suggested by the putative functions of the corresponding encoded proteins (e.g., secreted proteins) or their localization within previously identified selective sweeps. The adaptive roles in plant and anther-smut fungi interactions of candidate genes however need to be experimentally tested in future studies.

  7. Gene Presence–Absence Polymorphism in Castrating Anther-Smut Fungi: Recent Gene Gains and Phylogeographic Structure

    PubMed Central

    Rodríguez de la Vega, Ricardo C; Brandenburg, Jean-Tristan; Carpentier, Fantin; Giraud, Tatiana

    2018-01-01

    Abstract Gene presence–absence polymorphisms segregating within species are a significant source of genetic variation but have been little investigated to date in natural populations. In plant pathogens, the gain or loss of genes encoding proteins interacting directly with the host, such as secreted proteins, probably plays an important role in coevolution and local adaptation. We investigated gene presence–absence polymorphism in populations of two closely related species of castrating anther-smut fungi, Microbotryum lychnidis-dioicae (MvSl) and M. silenes-dioicae (MvSd), from across Europe, on the basis of Illumina genome sequencing data and high-quality genome references. We observed presence–absence polymorphism for 186 autosomal genes (2% of all genes) in MvSl, and only 51 autosomal genes in MvSd. Distinct genes displayed presence–absence polymorphism in the two species. Genes displaying presence–absence polymorphism were frequently located in subtelomeric and centromeric regions and close to repetitive elements, and comparison with outgroups indicated that most were present in a single species, being recently acquired through duplications in multiple-gene families. Gene presence–absence polymorphism in MvSl showed a phylogeographic structure corresponding to clusters detected based on SNPs. In addition, gene absence alleles were rare within species and skewed toward low-frequency variants. These findings are consistent with a deleterious or neutral effect for most gene presence–absence polymorphism. Some of the observed gene loss and gain events may however be adaptive, as suggested by the putative functions of the corresponding encoded proteins (e.g., secreted proteins) or their localization within previously identified selective sweeps. The adaptive roles in plant and anther-smut fungi interactions of candidate genes however need to be experimentally tested in future studies. PMID:29722826

  8. Screening strategies for a highly polymorphic gene: DHPLC analysis of the Fanconi anemia group A gene.

    PubMed

    Rischewski, J; Schneppenheim, R

    2001-01-30

    Patients with Fanconi anemia (Fanc) are at risk of developing leukemia. Mutations of the group A gene (FancA) are most common. A multitude of polymorphisms and mutations within the 43 exons of the gene are described. To examine the role of heterozygosity as a risk factor for malignancies, a partially automatized screening method to identify aberrations was needed. We report on our experience with DHPLC (WAVE (Transgenomic)). PCR amplification of all 43 exons from one individual was performed on one microtiter plate on a gradient thermocycler. DHPLC analysis conditions were established via melting curves, prediction software, and test runs with aberrant samples. PCR products were analyzed twice: native, and after adding a WT-PCR product. Retention patterns were compared with previously identified polymorphic PCR products or mutants. We have defined the mutation screening conditions for all 43 exons of FancA using DHPLC. So far, 40 different sequence variations have been detected in more than 100 individuals. The native analysis identifies heterozygous individuals, and the second run detects homozygous aberrations. Retention patterns are specific for the underlying sequence aberration, thus reducing sequencing demand and costs. DHPLC is a valuable tool for reproducible recognition of known sequence aberrations and screening for unknown mutations in the highly polymorphic FancA gene.

  9. HOTAIR gene polymorphisms contribute to increased neuroblastoma susceptibility in Chinese children.

    PubMed

    Yang, Xu; He, Jing; Chang, Yitian; Luo, Annie; Luo, Ailing; Zhang, Jiao; Zhang, Ruizhong; Xia, Huimin; Xu, Ling

    2018-06-15

    Neuroblastoma is the most frequently diagnosed extracranial solid tumor in children. Previous studies have shown that single-nucleotide polymorphisms in some genes are associated with the risk of multiple cancers, including neuroblastoma. Although Hox transcript antisense intergenic RNA (HOTAIR) gene polymorphisms have been investigated in a variety of cancers, to the authors' knowledge the relationships between HOTAIR gene polymorphisms and neuroblastoma susceptibility have not been reported to date. The objective of the current study was to evaluate the correlation between HOTAIR gene polymorphisms and neuroblastoma risk in Chinese children. The authors genotyped 6 polymorphisms (rs920778 A>G, rs12826786 C>T, rs4759314 A>G, rs7958904 G>C, rs874945 C>T, and rs1899663 C>A) of the HOTAIR gene in 2 Chinese populations including 393 neuroblastoma cases and 812 healthy controls. The strength of the associations was evaluated using odds ratios and 95% confidence intervals. Further stratification analyses were conducted to explore the association between the HOTAIR gene polymorphisms rs12826786 C>T, rs874945 C>T, and rs1899663 C>A with neuroblastoma susceptibility in terms of age, sex, clinical stage of disease, and sites of origin. The authors found that the rs12826786 C>T (P =.013), rs874945 C>T (P =.020), and rs1899663 C>A (P =.029) polymorphisms were significantly associated with increased neuroblastoma risk. In stratification analyses, these associations were more predominant in females and among patients with tumor in the retroperitoneal region or mediastinum. The remaining 3 polymorphisms were not found to be related to neuroblastoma susceptibility. The results of the current study verified that HOTAIR gene polymorphisms are associated with increased neuroblastoma risk and suggest that HOTAIR gene polymorphisms might be a potential biomarker for neuroblastoma susceptibility. Cancer 2018;124:2599-606. © 2018 American Cancer Society. © 2018 American Cancer Society.

  10. Serotyping of Streptococcus pneumoniae Based on Capsular Genes Polymorphisms

    PubMed Central

    Raymond, Frédéric; Boucher, Nancy; Allary, Robin; Robitaille, Lynda; Lefebvre, Brigitte; Tremblay, Cécile

    2013-01-01

    Streptococcus pneumoniae serotype epidemiology is essential since serotype replacement is a concern when introducing new polysaccharide-conjugate vaccines. A novel PCR-based automated microarray assay was developed to assist in the tracking of the serotypes. Autolysin, pneumolysin and eight genes located in the capsular operon were amplified using multiplex PCR. This step was followed by a tagged fluorescent primer extension step targeting serotype-specific polymorphisms. The tagged primers were then hybridized to a microarray. Results were exported to an expert system to identify capsular serotypes. The assay was validated on 166 cultured S. pneumoniae samples from 63 different serotypes as determined by the Quellung method. We show that typing only 12 polymorphisms located in the capsular operon allows the identification at the serotype level of 22 serotypes and the assignation of 24 other serotypes to a subgroup of serotypes. Overall, 126 samples (75.9%) were correctly serotyped, 14 were assigned to a member of the same serogroup, 8 rare serotypes were erroneously serotyped, and 18 gave negative serotyping results. Most of the discrepancies involved rare serotypes or serotypes that are difficult to discriminate using a DNA-based approach, for example 6A and 6B. The assay was also tested on clinical specimens including 43 cerebrospinal fluid samples from patients with meningitis and 59 nasopharyngeal aspirates from bacterial pneumonia patients. Overall, 89% of specimens positive for pneumolysin were serotyped, demonstrating that this method does not require culture to serotype clinical specimens. The assay showed no cross-reactivity for 24 relevant bacterial species found in these types of samples. The limit of detection for serotyping and S. pneumoniae detection was 100 genome equivalent per reaction. This automated assay is amenable to clinical testing and does not require any culturing of the samples. The assay will be useful for the evaluation of serotype

  11. The Evaluation of IL6 and ESR1 Gene Polymorphisms in Primary Dysmenorrhea.

    PubMed

    Ozsoy, Asker Zeki; Karakus, Nevin; Yigit, Serbulent; Cakmak, Bulent; Nacar, Mehmet Can; Yılmaz Dogru, Hatice

    2016-01-01

    Primary dysmenorrhea is the most common gynecological complaint with painful menstrual cramps in pelvis without any pathology. It affects about half of menstruating women, and it causes significant disruption in quality of life. We investigated the association between IL6 gene promoter and ESR1 gene XbaI and PvuII polymorphisms and primary dysmenorrhea. In this case-control study, 152 unrelated young women with primary dysmenorrhea and 150 unrelated healthy age-matched controls participated. Genomic DNA was isolated and IL6 and ESR1 gene polymorphisms were genotyped using PCR-based RFLP assay. The distribution of genotype and allele frequencies of IL6 gene promoter and ESR1 gene XbaI polymorphisms were not statistically different between patients and controls (p > 0.05). However, the genotype and allele frequencies of ESR1 gene PvuII polymorphism showed statistically significant differences between primary dysmenorrhea patients and controls (p = 0.009 and p = 0.021, respectively). Statistically significant associations were also observed between age and married status of primary dysmenorrhea patients and ESR1 gene PvuII polymorphism (p = 0.044 and p = 0.023, respectively). In combined genotype analyses, AG at ESR1 XbaI and TC at ESR1 PvuII loci encoded a p-value of 0.027. Thus, individuals who are heterozygote at both loci have a lower risk of developing primary dysmenorrhea. Our study suggests no strong association between IL6 gene promoter and ESR1 gene XbaI polymorphisms and primary dysmenorrhea in Turkish women. However, ESR1 gene PvuII polymorphism showed statistically significant differences between primary dysmenorrhea patients and controls. The potential association between ESR1 gene PvuII polymorphism and age and married status of dysmenorrhea patients deserves further consideration.

  12. The effects of gene polymorphisms on glioma prognosis.

    PubMed

    Cui, Ying; Li, Guolin; Yan, Mengdan; Li, Jing; Jin, Tianbo; Li, Shanqu; Mu, Shijie

    2017-11-01

    Malignant gliomas are the most common primary brain tumors. Various genetic factors play important roles in the development and prognosis of glioma. The present study focuses on the impact of MPHOSPH6, TNIP1 and several other genes (ACYP2, NAF1, TERC, TERT, OBFC1, ZNF208 and RTEL1) on telomere length and how this affects the prognosis of glioma. Forty-three polymorphisms in nine genes from 605 glioma patients were selected. The association between genotype and survival outcome was analyzed using the Kaplan-Meier method, Cox regression analysis and the log-rank test. The 1-year overall survival (OS) rates of patients younger than 40 years of age was higher compared to those in patients older than 40 years of age. The 1-year OS rate of patients who underwent total resection was higher than that of patients whose gliomas were not completely resected. The 1-year OS rates of patients undergoing chemotherapy and of patients who did not undergo chemotherapy were 39.90% and 26.80%, respectively. Univariate analyses showed that ACYP2 rs12615793 and TERT rs2853676 loci affected progression-free survival in glioma patients; both ZNF208 rs8105767 and ACYP2 rs843720 affected the OS of patients with low-grade gliomas. Multivariate analyses suggested that MPHOSPH6 rs1056629 and rs1056654, and TERT rs2853676 loci were associated with good prognoses of patients with glioma or high-grade gliomas, whereas ZNF208 rs8105767 was associated with good prognosis of patients with low-grade glioma. Age, surgical resection and chemotherapy influenced the survival rates of glioma patients. TERT, MPHOSPH6, ACYP2 and ZNF208 genes were found to affect glioma prognosis. Copyright © 2017 John Wiley & Sons, Ltd.

  13. Genetic association of cyclooxygenase-2 gene polymorphisms with Parkinson's disease susceptibility in Chinese Han population.

    PubMed

    Dai, Yi; Wu, Yuquan; Li, Yansheng

    2015-01-01

    The aim of this study was to explore the genetic association of cyclooxygenase-2 (COX2) gene promoter region polymorphisms with Parkinson's disease (PD) susceptibility in Chinese Han population. The genotyping of COX2 gene polymorphisms was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 122 patients with PD and 120 healthy persons. The association strength of gene polymorphism with disease was measured by odds ratio (OR) and 95% confidence interval (95% CI) calculated using χ(2) test which also evaluated the Hardy-Weinberg equilibrium (HWE) of gene polymorphism in controls. The linkage disequilibrium and haplotype were also analyzed as evidence in the analysis of association. On condition that the genotypes distributions of COX2 -1290A>G, -1195G>A, -765G>C in the control group all conformed to HWE, however, only the homozygous genotype AA of -1195G>A polymorphism showed an association with PD (OR=0.432, 95% CI=0.196-0.950). In addition, in haplotype analysis, G-A-C haplotype frequency in cases was significantly lower than the controls, compared with the common haplotype A-G-G (P=0.031, OR=0.375, 95% CI=0.149-0.940). COX2 -1195G>A polymorphism might play a protective role in the onset of PD and G-A-C haplotype in this three promoter region polymorphisms also showed a negative association.

  14. Polymorphisms in Dopamine System Genes Are Associated with Individual Differences in Attention in Infancy

    ERIC Educational Resources Information Center

    Holmboe, Karla; Nemoda, Zsofia; Fearon, R. M. Pasco; Csibra, Gergely; Sasvari-Szekely, Maria; Johnson, Mark H.

    2010-01-01

    Knowledge about the functional status of the frontal cortex in infancy is limited. This study investigated the effects of polymorphisms in four dopamine system genes on performance in a task developed to assess such functioning, the Freeze-Frame task, at 9 months of age. Polymorphisms in the catechol-O-methyltransferase ("COMT") and the…

  15. Association of ghrelin receptor gene polymorphism with bulimia nervosa in a Japanese population.

    PubMed

    Miyasaka, K; Hosoya, H; Sekime, A; Ohta, M; Amono, H; Matsushita, S; Suzuki, K; Higuchi, S; Funakoshi, A

    2006-09-01

    Eating disorders (EDs) have a highly heterogeneous etiology and multiple genetic factors might contribute to their pathogenesis. Ghrelin, a novel growth hormone-releasing peptide, enhances appetite and increases food intake, and human ghrelin plasma levels are inversely correlated with body mass index. In the present study, we examined the 171T/C polymorphism of the ghrelin receptor (growth hormone secretagogue receptor, GHSR) gene in patients diagnosed with EDs, because the subjects having ghrelin gene polymorphism (Leu72Met) was not detected in a Japanese population, previously. In addition, beta3 adrenergic receptor gene polymorphism (Try64Arg) and cholecystokinin (CCK)-A receptor (R) gene polymorphism (-81A/G, -128G/T), which are both associated with obesity, were investigated. The subjects consisted of 228 Japanese patients with EDs [96 anorexia nervosa (AN), 116 bulimia nervosa (BN) and 16 not otherwise specified (NOS)]. The age- and gender-matched control group consisted of 284 unrelated Japanese subjects. The frequency of the CC type of the GHSR gene was significantly higher in BN subjects than in control subjects (chi(2) = 4.47, p = 0.035, odds ratio = 2.05, Bonferroni correction: p = 0.070), while the frequency in AN subjects was not different from that in controls. The distribution of neither beta3 adrenergic receptor gene nor CCK-AR polymorphism differed between EDs and control subjects. Therefore, the CC type of GHSR gene polymorphism (171T/C) is a risk factor for BN, but not for AN.

  16. DNA mismatch repair gene polymorphisms affect survival in pancreatic cancer.

    PubMed

    Dong, Xiaoqun; Li, Yanan; Hess, Kenneth R; Abbruzzese, James L; Li, Donghui

    2011-01-01

    DNA mismatch repair (MMR) maintains genomic stability and mediates cellular response to DNA damage. We aim to demonstrate whether MMR genetic variants affect overall survival (OS) in pancreatic cancer. Using the Sequenom method in genomic DNA, we retrospectively genotyped 102 single-nucleotide polymorphisms (SNPs) of 13 MMR genes from 706 patients with pancreatic adenocarcinoma seen at The University of Texas MD Anderson Cancer Center. Association between genotype and OS was evaluated using multivariable Cox proportional hazard regression models. At a false discovery rate of 1% (p ≤ .0015), 15 SNPs of EXO1, MLH1, MSH2, MSH3, MSH6, PMS2, PMS2L3, TP73, and TREX1 in patients with localized disease (n = 333) and 6 SNPs of MSH3, MSH6, and TP73 in patients with locally advanced or metastatic disease (n = 373) were significantly associated with OS. In multivariable Cox proportional hazard regression models, SNPs of EXO1, MSH2, MSH3, PMS2L3, and TP73 in patients with localized disease, MSH2, MSH3, MSH6, and TP73 in patients with locally advanced or metastatic disease, and EXO1, MGMT, MSH2, MSH3, MSH6, PMS2L3, and TP73 in all patients remained significant predictors for OS (p ≤ .0015) after adjusting for all clinical predictors and all SNPs with p ≤ .0015 in single-locus analysis. Sixteen haplotypes of EXO1, MLH1, MSH2, MSH3, MSH6, PMS2, PMS2L3, RECQL, TP73, and TREX1 significantly correlated with OS in all patients (p ≤ .001). MMR gene variants may have potential value as prognostic markers for OS in pancreatic cancer patients.

  17. Association of ACE Gene I/D polymorphism with migraine in Kashmiri population.

    PubMed

    Wani, Irfan Yousuf; Sheikh, Saleem; Shah, Zafar Amin; Pandith, Arshid A; Wani, Mushtaq; Asimi, Ravouf; Wani, Maqbool; Sheikh, Shahnawaz; Mehraj, Iqra

    2016-01-01

    Migraine is a complex, recurrent headache disorder that is one of the most common complaints in neurology practice. The role of various genes in its pathogenesis is being studied. We did this study to see whether an association exists between ACE gene I/D polymorphism and migraine in our region. The study included 100 patients diagnosed with migraine and 121 healthy controls. The study subject were age and gender matched. The analysis was based on Polymerase Chain Reaction (PCR) and included following steps: DNA extraction from blood, PCR and Restriction Fragment Length Polymorphism (RFLP). Out of 100 cases, 69 were females and 31 were males. Fifty-seven were having migraine without aura and 43 had migraine with aura. 45 of the cases had II polymorphism, 40 had ID polymorphism and 15 had DD polymorphism in ACE gene. We were not able to find a statistically significant association between ACE gene I/D polymorphism with migraine. The reason for difference in results between our study and other studies could be because of different ethnicity in study populations. So a continuous research is needed in this regard in order to find the genes and different polymorphism that increase the susceptibility of Kashmiri population to migraine.

  18. Androgen Receptor Gene Polymorphism, Aggression, and Reproduction in Tanzanian Foragers and Pastoralists

    PubMed Central

    Butovskaya, Marina L.; Lazebny, Oleg E.; Vasilyev, Vasiliy A.; Dronova, Daria A.; Karelin, Dmitri V.; Mabulla, Audax Z. P.; Shibalev, Dmitri V.; Shackelford, Todd K.; Fink, Bernhard; Ryskov, Alexey P.

    2015-01-01

    The androgen receptor (AR) gene polymorphism in humans is linked to aggression and may also be linked to reproduction. Here we report associations between AR gene polymorphism and aggression and reproduction in two small-scale societies in northern Tanzania (Africa)—the Hadza (monogamous foragers) and the Datoga (polygynous pastoralists). We secured self-reports of aggression and assessed genetic polymorphism of the number of CAG repeats for the AR gene for 210 Hadza men and 229 Datoga men (aged 17–70 years). We conducted structural equation modeling to identify links between AR gene polymorphism, aggression, and number of children born, and included age and ethnicity as covariates. Fewer AR CAG repeats predicted greater aggression, and Datoga men reported more aggression than did Hadza men. In addition, aggression mediated the identified negative relationship between CAG repeats and number of children born. PMID:26291982

  19. Metabolism and gene polymorphisms of the folate pathway in Brazilian women with history of recurrent abortion.

    PubMed

    Boas, Wendell Vilas; Gonçalves, Rozana Oliveira; Costa, Olívia Lúcia Nunes; Goncalves, Marilda Souza

    2015-02-01

    To investigate the association between polymorphisms in genes that encode enzymes involved in folate- and vitamin B12-dependent homocysteine metabolism and recurrent spontaneous abortion (RSA). We investigated the C677T and A1298C polymorphisms of the methylenetetrahydrofalate reductase gene (MTHFR), the A2756G polymorphism of the methionine synthase gene (MS) and the 844ins68 insertion of the cystathionine beta synthetase gene (CBS). The PCR technique followed by RFLP was used to assess the polymorphisms; the serum levels of homocysteine, vitamin B12 and folate were investigated by chemiluminescence. The EPI Info Software version 6.04 was used for statistical analysis. Parametric variables were compared by Student's t-test and nonparametric variables by the Wilcoxon rank sum test. The frequencies of gene polymorphisms in 89 women with a history of idiopathic recurrent miscarriage and 150 controls were 19.1 and 19.6% for the C677T, insertion, 20.8 and 26% for the A1298C insertion, 14.2 and 21.9% for the A2756G insertion, and 16.4 and 18% for the 844ins68 insertion, respectively. There were no significant differences between case and control groups in any of the gene polymorphisms investigated. However, the frequency of the 844ins68 insertion in the CBS gene was higher among women with a history of loss during the third trimester of pregnancy (p=0.003). Serum homocysteine, vitamin B12 and folate levels id not differ between the polymorphisms studied in the case and control groups. However, linear regression analysis showed a dependence of serum folate levels on the maintenance of tHcy levels. The investigated gene polymorphisms and serum homocysteine, vitamin B12 and folate levels were not associated with idiopathic recurrent miscarriage in the present study. Further investigations are needed in order to confirm the role of the CBS 844ins68 insertion in recurrent miscarriage.

  20. Blood lead levels, iron metabolism gene polymorphisms and homocysteine: a gene-environment interaction study.

    PubMed

    Kim, Kyoung-Nam; Lee, Mee-Ri; Lim, Youn-Hee; Hong, Yun-Chul

    2017-12-01

    Homocysteine has been causally associated with various adverse health outcomes. Evidence supporting the relationship between lead and homocysteine levels has been accumulating, but most prior studies have not focused on the interaction with genetic polymorphisms. From a community-based prospective cohort, we analysed 386 participants (aged 41-71 years) with information regarding blood lead and plasma homocysteine levels. Blood lead levels were measured between 2001 and 2003, and plasma homocysteine levels were measured in 2007. Interactions of lead levels with 42 genotyped single-nucleotide polymorphisms (SNPs) in five genes ( TF , HFE , CBS , BHMT and MTR ) were assessed via a 2-degree of freedom (df) joint test and a 1-df interaction test. In secondary analyses using imputation, we further assessed 58 imputed SNPs in the TF and MTHFR genes. Blood lead concentrations were positively associated with plasma homocysteine levels (p=0.0276). Six SNPs in the TF and MTR genes were screened using the 2-df joint test, and among them, three SNPs in the TF gene showed interactions with lead with respect to homocysteine levels through the 1-df interaction test (p<0.0083). Seven SNPs in the MTHFR gene were associated with homocysteine levels at an α-level of 0.05, but the associations did not persist after Bonferroni correction. These SNPs did not show interactions with lead levels. Blood lead levels were positively associated with plasma homocysteine levels measured 4-6 years later, and three SNPs in the TF gene modified the association. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  1. Association of Duffy Blood Group Gene Polymorphisms with IL8 Gene in Chronic Periodontitis

    PubMed Central

    Sippert, Emília Ângela; de Oliveira e Silva, Cléverson; Visentainer, Jeane Eliete Laguila; Sell, Ana Maria

    2013-01-01

    The antigens of the Duffy blood group system (DARC) act as a receptor for the interleukin IL-8. IL-8 plays an important role in the pathogenesis of chronic periodontitis due to its chemotactic properties on neutrophils. The aim of this study was to investigate a possible association of Duffy blood group gene polymorphisms with the -353T>A, -845T>C and -738T>A SNPs of the IL8 gene in chronic periodontitis. One hundred and twenty-four individuals with chronic periodontitis and 187 controls were enrolled. DNA was extracted using the salting-out method. The Duffy genotypes and IL8 gene promoter polymorphisms were investigated by PCR-RFLP. Statistical analyses were conducted using the Chi square test with Yates correction or Fisher's Exact Test, and the possibility of associations were evaluated by odds ratio with a 95% confidence interval. When analyzed separately, for the Duffy blood group system, differences in the genotype and allele frequencies were not observed between all the groups analyzed; and, in nonsmokers, the -845C allele (3.6% vs. 0.4%), -845TC genotype (7.3% vs. 0.7%) and the CTA haplotype (3.6% vs. 0.4%) were positively associated with chronic periodontitis. For the first time to our knowledge, the polymorphisms of erythroid DARC plus IL8 -353T>A SNPs were associated with chronic periodontitis in Brazilian individuals. In Afro-Brazilians patients, the FY*02N.01 with IL8 -353A SNP was associated with protection to chronic periodontitis. PMID:24386171

  2. Association of duffy blood group gene polymorphisms with IL8 gene in chronic periodontitis.

    PubMed

    Sippert, Emília Ângela; de Oliveira e Silva, Cléverson; Visentainer, Jeane Eliete Laguila; Sell, Ana Maria

    2013-01-01

    The antigens of the Duffy blood group system (DARC) act as a receptor for the interleukin IL-8. IL-8 plays an important role in the pathogenesis of chronic periodontitis due to its chemotactic properties on neutrophils. The aim of this study was to investigate a possible association of Duffy blood group gene polymorphisms with the -353T>A, -845T>C and -738T>A SNPs of the IL8 gene in chronic periodontitis. One hundred and twenty-four individuals with chronic periodontitis and 187 controls were enrolled. DNA was extracted using the salting-out method. The Duffy genotypes and IL8 gene promoter polymorphisms were investigated by PCR-RFLP. Statistical analyses were conducted using the Chi square test with Yates correction or Fisher's Exact Test, and the possibility of associations were evaluated by odds ratio with a 95% confidence interval. When analyzed separately, for the Duffy blood group system, differences in the genotype and allele frequencies were not observed between all the groups analyzed; and, in nonsmokers, the -845C allele (3.6% vs. 0.4%), -845TC genotype (7.3% vs. 0.7%) and the CTA haplotype (3.6% vs. 0.4%) were positively associated with chronic periodontitis. For the first time to our knowledge, the polymorphisms of erythroid DARC plus IL8 -353T>A SNPs were associated with chronic periodontitis in Brazilian individuals. In Afro-Brazilians patients, the FY*02N.01 with IL8 -353A SNP was associated with protection to chronic periodontitis.

  3. Cytokine gene polymorphisms in Italian preterm infants: association between interleukin-10 -1082 G/A polymorphism and respiratory distress syndrome.

    PubMed

    Capasso, Mario; Avvisati, Rosa Anna; Piscopo, Carmelo; Laforgia, Nicola; Raimondi, Francesco; de Angelis, Filomena; Iolascon, Achille

    2007-03-01

    In this study, we determined the genotype frequencies of polymorphisms of cytokine genes and investigated their association with the risk of respiratory distress syndrome (RDS) in preterm infants. Genetic polymorphisms in the cytokines interleukin (IL)-10, IL-8, and tumor necrosis factor (TNF) alpha, were studied in 342 white Italian newborns (112 without RDS, 66 prematurely born with RDS, and 164 infants born at term who were included as healthy controls). The polymorphisms were analyzed by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP). The IL-10 mRNA levels were analyzed according to genotype by quantitative real-time PCR (QRT-PCR) in Epstein-Barr virus-transformed lymphoblastoid cell lines (EBV-LCLs) of 42 full-term healthy infants. Logistic regression analysis demonstrated the risk of RDS to be significantly lower in preterm infants with an IL-10 -1082 GG/GA genotype than in those with an AA genotype [odds ratio (OR) = 0.48, 95% confidence interval (CI): 0.24-0.95, p = 0.03]. QRT-PCR analyses showed that the IL-10 mRNA levels were significantly higher in 27 IL-10 -1082 GG/GA carriers compared with 15 IL-10 -1082 AA carriers (p = 0.03). We conclude that the IL-10 -1082 GG/GA polymorphism may have a role in RDS development in premature infants.

  4. Polymorphism and selection in the major histocompatibility complex DRA and DQA genes in the family Equidae.

    PubMed

    Janova, Eva; Matiasovic, Jan; Vahala, Jiri; Vodicka, Roman; Van Dyk, Enette; Horin, Petr

    2009-07-01

    The major histocompatibility complex genes coding for antigen binding and presenting molecules are the most polymorphic genes in the vertebrate genome. We studied the DRA and DQA gene polymorphism of the family Equidae. In addition to 11 previously reported DRA and 24 DQA alleles, six new DRA sequences and 13 new DQA alleles were identified in the genus Equus. Phylogenetic analysis of both DRA and DQA sequences provided evidence for trans-species polymorphism in the family Equidae. The phylogenetic trees differed from species relationships defined by standard taxonomy of Equidae and from trees based on mitochondrial or neutral gene sequence data. Analysis of selection showed differences between the less variable DRA and more variable DQA genes. DRA alleles were more often shared by more species. The DQA sequences analysed showed strong amongst-species positive selection; the selected amino acid positions mostly corresponded to selected positions in rodent and human DQA genes.

  5. Polymorphisms at the Ligand Binding Site of the Vitamin D Receptor Gene and Osteomalacia

    PubMed Central

    Ak, Duygu Gezen; Kahraman, Hakkí; Dursun, Erdinç; Duman, Belgin Süsleyici; Erensoy, Nevin; Alagöl, Faruk; Tanakol, Refik; Yılmazer, Selma

    2005-01-01

    Vitamin D receptor (VDR) gene polymorphisms have been suggested as possible determinants of bone mineral density (BMD) and calcium metabolism. In this study, our aim was to determine whether there is an association between VDR gene polymorphism and osteomalacia or not. We determined ApaI and TaqI polymorphisms in the vitamin D receptor gene in 24 patients with osteomalacia and 25 age-matched healthy controls. Serum calcium, phosphorus, ALP, PTH, 25OHD levels were also examined. We used PCR and RFLP methods to test for an association between osteomalacia and polymorphisms within, intron 8 and exon 9 of the VDR gene. When the control and patients were compared for their ApaI and TaqI genotypes there was no relationship between VDR gene allelic polymorphisms and osteomalacia. Whereas a nearly significant difference for A allele was found in the allellic distribution of the patients (p = 0.08). Also no association between biochemical data and VDR gene polymorphisms was observed. PMID:16403954

  6. Excess amino acid polymorphism in mitochondrial DNA: contrasts among genes from Drosophila, mice, and humans.

    PubMed

    Rand, D M; Kann, L M

    1996-07-01

    Recent studies of mitochondrial DNA (mtDNA) variation in mammals and Drosophila have shown an excess of amino acid variation within species (replacement polymorphism) relative to the number of silent and replacement differences fixed between species. To examine further this pattern of nonneutral mtDNA evolution, we present sequence data for the ND3 and ND5 genes from 59 lines of Drosophila melanogaster and 29 lines of D. simulans. Of interest are the frequency spectra of silent and replacement polymorphisms, and potential variation among genes and taxa in the departures from neutral expectations. The Drosophila ND3 and ND5 data show no significant excess of replacement polymorphism using the McDonald-Kreitman test. These data are in contrast to significant departures from neutrality for the ND3 gene in mammals and other genes in Drosophila mtDNA (cytochrome b and ATPase 6). Pooled across genes, however, both Drosophila and human mtDNA show very significant excesses of amino acid polymorphism. Silent polymorphisms at ND5 show a significantly higher variance in frequency than replacement polymorphisms, and the latter show a significant skew toward low frequencies (Tajima's D = -1.954). These patterns are interpreted in light of the nearly neutral theory where mildly deleterious amino acid haplotypes are observed as ephemeral variants within species but do not contribute to divergence. The patterns of polymorphism and divergence at charge-altering amino acid sites are presented for the Drosophila ND5 gene to examine the evolution of functionally distinct mutations. Excess charge-altering polymorphism is observed at the carboxyl terminal and excess charge-altering divergence is detected at the amino terminal. While the mildly deleterious model fits as a net effect in the evolution of nonrecombining mitochondrial genomes, these data suggest that opposing evolutionary pressures may act on different regions of mitochondrial genes and genomes.

  7. Association of HS6ST3 gene polymorphisms with obesity and triglycerides: gene x gender interaction.

    PubMed

    Wang, Ke-Sheng; Wang, Liang; Liu, Xuefeng; Zeng, Min

    2013-12-01

    The heparan sulfate 6-O-sulfotransferase 3 (HS6ST3) gene is involved in heparan sulphate and heparin metabolism, and has been reported to be associated with diabetic retinopathy in type 2 diabetes.We hypothesized that HS6ST3 gene polymorphisms might play an important role in obesity and related phenotypes (such as triglycerides). We examined genetic associations of 117 single-nucleotide polymorphisms (SNPs) within the HS6ST3 gene with obesity and triglycerides using two Caucasian samples: the Marshfield sample (1442 obesity cases and 2122 controls), and the Health aging and body composition (Health ABC) sample (305 cases and 1336 controls). Logistic regression analysis of obesity as a binary trait and linear regression analysis of triglycerides as a continuous trait, adjusted for age and sex, were performed using PLINK. Single marker analysis showed that six SNPs in the Marshfield sample and one SNP in the Health ABC sample were associated with obesity (P < 0.05). SNP rs535812 revealed a stronger association with obesity in meta-analysis of these two samples (P = 0.0105). The T-A haplotype from rs878950 and rs9525149 revealed significant association with obesity in the Marshfield sample (P = 0.012). Moreover, nine SNPs showed associations with triglycerides in the Marshfield sample (P < 0.05) and the best signal was rs1927796 (P = 0.00858). In addition, rs7331762 showed a strong gene x gender interaction (P = 0.00956) for obesity while rs1927796 showed a strong gene x gender interaction (P = 0.000625) for triglycerides in the Marshfield sample. These findings contribute new insights into the pathogenesis of obesity and triglycerides and demonstrate the importance of gender differences in the aetiology.

  8. Influence of ghrelin gene polymorphisms on hypertension and atherosclerotic disease.

    PubMed

    Berthold, Heiner K; Giannakidou, Eleni; Krone, Wilhelm; Trégouët, David-Alexandre; Gouni-Berthold, Ioanna

    2010-02-01

    Ghrelin is involved in several metabolic and cardiovascular processes. Recent evidence suggests its involvement in blood pressure regulation and hypertension. The aim of the study was to determine associations of single-nucleotide polymorphisms (SNPs) and haplotypes of the ghrelin gene (GHRL) with hypertension and atherosclerotic disease. Six GHRL SNPs (rs27647, rs26802, rs34911341, rs696217, rs4684677 and a -473G/A (with no assigned rsID)) were investigated in a sample of 1143 hypertensive subjects and 1489 controls of Caucasian origin. Both single-locus and haplotype association analyses were performed. In single-locus analyses, only the non-synonymous rs34911341 was associated with hypertension (odds ratio (OR)=1.95 (95% confidence interval (CI): 1.26-3.02), P=0.003). Six common haplotypes with frequency >1% were inferred from the studied GHRL SNPs, and their frequency distribution was significantly different between hypertensive subjects and controls (chi(2)=12.96 with 5 d.f. (degree of freedom), P=0.024). The effect of rs26802 was found to be significantly (P=0.017) modulated by other GHRL SNPs, as its C allele conferred either an increased risk (OR=1.30 (1.08-1.57), P=0.005) or a decreased risk (OR=0.50 (0.23-1.06), P=0.07) of hypertension according to the two different haplotypes on which it can be found. No association of GHRL SNPs or haplotypes with atherosclerotic disease was observed. In conclusion, we observed statistical evidence for association between GHRL SNPs and risk of hypertension.

  9. Estrogen Receptor 1 ( ESR1) Gene Polymorphisms and Obesity Phenotypes in a Population of Young Adults.

    PubMed

    Correa-Rodríguez, María; Schmidt-RioValle, Jacqueline; González-Jiménez, Emilio; Rueda-Medina, Blanca

    2017-06-01

    Obesity is considered an increasingly serious health problem determined by multiple genetic and environmental factors. Estrogens have been found to play a major role in body weight and adiposity regulation through estrogen receptor 1 ( ESR1). The aim of this study was to determine whether genotype and haplotype frequencies of ESR1 polymorphisms are associated with body composition measures in a population of 572 young adults. A lack of significant association between genotypes of ESR1 gene polymorphisms and obesity phenotypes was seen after adjustment for confounding factors. Linkage disequilibrium (LD) analysis identified a single LD block for the ESR1 gene including PvuII and XbaI single-nucleotide polymorphisms (SNPs) (pairwise r 2 = .66). None of the haplotypes identified revealed statistically significant associations with any of the obesity phenotypes. Our results suggest that polymorphisms of the ESR1 gene do not contribute significantly to the genetic risk for obesity phenotypes in a population of young Caucasian adults.

  10. No association between polymorphisms in the DDC gene and paranoid schizophrenia in a northern Chinese population.

    PubMed

    Zhang, Boyu; Jia, Yanbin; Yuan, Yanbo; Yu, Xin; Xu, Qi; Shen, Yucun; Shen, Yan

    2004-09-01

    Several lines of evidence suggest that dysfunctions of neurotransmitters are associated with schizophrenia. DOPA decarboxylase (DDC) is an enzyme involved directly in the synthesis of dopamine and serotonin, and indirectly in the synthesis of noradrenaline. Therefore, the DDC gene can be considered a candidate gene for schizophrenia. We performed an association study between three single nucleotide polymorphisms in the DDC gene and paranoid schizophrenia. However, in our study no significant differences were found in the genotype distributions and allele frequencies between 80 paranoid schizophrenics and 108 controls for any of the polymorphisms. Neither did the haplotypes of the single nucleotide polymorphisms show any association with paranoid schizophrenia. Therefore, we conclude that the polymorphisms studied do not play a major role in paranoid schizophrenia pathogenesis in the population investigated.

  11. Prolactin receptor gene polymorphism and the risk of recurrent pregnancy loss: a case-control study.

    PubMed

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

    2018-02-01

    Since the first study was published reporting the candidate association between the prolactin receptor gene intron C/T polymorphism (rs37389) and recurrent miscarriage, no replication study has been performed. In this study, we investigated the role of the prolactin receptor gene C/T polymorphism in 311 Korean women with recurrent pregnancy loss and 314 controls. Genotyping for prolactin receptor gene intron C/T polymorphism was performed using a TaqMan assay. The significance of difference in the genotype distribution was assessed using a chi-square test, and continuous variables were compared using a Student's t-test. The genotype distribution of the prolactin receptor gene C/T polymorphism in the recurrent pregnancy loss group did not differ from that in the control group (CC/CT/TT rates were 49.8%/41.5%/8.7% and 52.5%/37.6%/9.9% for the recurrent pregnancy loss patient and control groups, respectively, p = .587). When the analysis was restricted to patients with three or more consecutive spontaneous miscarriages or patients without prior live birth, there were also no differences in the genotype distribution between these subgroups and controls. In conclusion, the findings of the current study suggest that the prolactin receptor gene intron C/T polymorphism is not a major determinant of the development of recurrent pregnancy loss. Impact statement What is already known: Many studies have investigated whether there is a genetic component for the risk of recurrent pregnancy loss. Recently, one study investigated whether genetic polymorphisms involved in the regulation of the hypothalamic-pituitary-ovarian axis would be associated with recurrent miscarriage. Among 35 polymorphisms in 20 candidate genes, genotype distribution with regard to the prolactin receptor gene intron C/T polymorphism (rs37389) differed between the recurrent miscarriage and the control groups. Since this study reporting the candidate association between the prolactin receptor gene and

  12. Study of the HFE gene common polymorphisms in French patients with sporadic amyotrophic lateral sclerosis.

    PubMed

    Praline, Julien; Blasco, Hélène; Vourc'h, Patrick; Rat, Valérian; Gendrot, Chantal; Camu, William; Andres, Christian R

    2012-06-15

    Our objective was to investigate whether the C282Y (p.Cys 282 Tyr) and H63D (p. His 63 Asp) HFE polymorphisms were associated with sporadic amyotrophic lateral sclerosis (SALS) in the French population. We searched for a relation of HFE polymorphisms with the clinical characteristics of the disease. The HFE polymorphisms were studied in 824 patients with SALS and 583 controls. We compared the frequency of the polymorphisms between SALS and controls groups by univariate and multivariate statistics, taking into account gender, site, age-at-onset and survival. We did not observe significant difference in the frequency of H63D polymorphism between SALS and control group. We observed a significant difference for C282Y between patients and controls with a low frequency of the Y allele in patients (3.2%) compared to our control group (5.9%). Disease duration, distribution of gender, site-of-onset, age-at-onset did not differ between groups taking into account genotypes of each polymorphism. Our results in this large cohort of ALS patients indicate that H63D polymorphism is not associated with SALS in the French population. This conclusion does not exclude a weak effect of the HFE gene polymorphisms in certain ALS populations, or an effect of other rare HFE gene variants. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Polymorphisms in genes encoding dopamine signalling pathway and risk of alcohol dependence: a systematic review.

    PubMed

    Bhaskar, Lakkakula V K S; Kumar, Shanmugasundaram Arun

    2014-04-01

    Alcohol dependence (AD) is one of the major elements that significantly influence drinking pattern that provoke the alcohol-induced organ damage. The structural and neurophysiologic abnormalities in the frontal lobes of chronic alcoholics were revealed by magnetic resonance imaging scans. It is well known that candidate genes involved in dopaminergic pathway are of immense interest to the researchers engaged in a wide range of addictive disorders. Dopaminergic pathway gene polymorphisms are being extensively studied with respect to addictive and behavioral disorders. From the broad literature available, the current review summarizes the specific polymorphisms of dopaminergic genes that play a role in alcohol dependence. No evidence indicating any strong association between AD and polymorphisms of dopamine pathway genes has emerged from the literature. Further studies are warranted, considering a range of alcohol-related traits to determine the genes that influence alcohol dependence.

  14. Association analysis of the functional MAOA gene promoter and MAOB gene intron 13 polymorphisms in tension type headache patients.

    PubMed

    Edgnülü, Tuba G; Özge, Aynur; Erdal, Nurten; Kuru, Oktay; Erdal, Mehmet E

    2014-01-01

    Monoamine oxidase (MAO) enzymes play an important role in the etiology of many neurological diseases. Tension type headache (TTH) treatments contain inhibitors for selective re-uptake of serotonin and monoamine oxidase inhibitors. MAO (EC 1.4.3.4) has two isoenzymes known as MAOA and MAOB. A promoter polymorphism of a variable number of tandem repeats (VNTR) in the MAOA gene seems to affect MAOA transcriptional activity in vitro. Also, G/A polymorphism in intron 13 (rs1799836) of the MAOB gene have been previously found to be associated with the variability of MAOB enzyme activity. The aim of our study was to investigate a possible association of monoamine oxidase (MAOA and MAOB) gene polymorphisms in tension type headache. MAO gene polymorphisms were examined in a group of 120 TTH patients and in another 168 unrelated healthy volunteers (control group). MAOA promoter and MAOB intron 13 polymorphisms were genotyped using PCR-based methods. An overall comparison between the genotype of MAOA and MAOB genes and allele frequencies of the patients and the control group did not reveal any statistically significant difference between the patients and the control group (p=0.162). Factors like estrogen dosage, the limited number of male patients and other genes' neurotransmitters involved in the etiology of TTH could be responsible for our non-significant results.

  15. Clinical relevance of IL-6 gene polymorphism in severely injured patients

    PubMed Central

    Jeremić, Vasilije; Alempijević, Tamara; Mijatović, Srđan; Šijački, Ana; Dragašević, Sanja; Pavlović, Sonja; Miličić, Biljana; Krstić, Slobodan

    2014-01-01

    In polytrauma, injuries that may be surgically treated under regular circumstances due to a systemic inflammatory response become life-threatening. The inflammatory response involves a complex pattern of humoral and cellular responses and the expression of related factors is thought to be governed by genetic variations. This aim of this paper is to examine the influence of interleukin (IL) 6 single nucleotide polymorphism (SNP) -174C/G and -596G/A on the treatment outcome in severely injured patients. Forty-seven severely injured patients were included in this study. Patients were assigned an Injury Severity Score. Blood samples were drawn within 24 h after admission (designated day 1) and on subsequent days (24, 48, 72 hours and 7days) of hospitalization. The IL-6 levels were determined through ELISA technique. Polymorphisms were analyzed by a method of Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR). Among subjects with different outcomes, no statistically relevant difference was found with regards to the gene IL-6 SNP-174G/C polymorphism. More than a half of subjects who died had the SNP-174G/C polymorphism, while this polymorphism was represented in a slightly lower number in survivors. The incidence of subjects without polymorphism and those with heterozygous and homozygous gene IL-6 SNP-596G/A polymorphism did not present statistically significant variations between survivors and those who died. The levels of IL-6 over the observation period did not present any statistically relevant difference among subjects without the IL-6 SNP-174 or IL-6 SNP -596 gene polymorphism and those who had either a heterozygous or a homozygous polymorphism. PMID:24856384

  16. Is M235T polymorphism of the angiotensinogen gene involved in the development of endometriosis?

    PubMed

    Kowalczyńska, Liliana J; Ferenc, Tomasz; Wojciechowski, Michał; Mordalska, Anna; Pogoda, Krzysztof; Malinowski, Andrzej

    2017-01-01

    The aim of the study was to analyze the M235T polymorphism of the angiotensinogen (AGT) gene in women with endometriosis and to identify correlations between identified genotypes and the disease progression, its stage and clinical course as well as to evaluate the prognostic value of the investigated polymorphism in patients with endometriosis treated for infertility. The study group consisted of 241 women with minimal to severe stage of endometriosis, the control group (without endometriosis) - 127. The molecular analysis was performed by PCR-RFLP technique. The analysis of the frequency of genotypes and alleles of M235T polymorphism showed no significant differences between the study and the control groups and between the severity grades of the disease (p > 0.05). No such differences were reported in the case of different localizations of the disease lesions, either. Evaluation of the correlations related to pain accompanying endometriosis did not demonstrate association with any genotypes of the analyzed AGT gene poly-morphism. Comparison of the results obtained in the group in which infertility treatment was successful (n = 54) and in those who failed to conceive (n = 73) did not show the correlation between the investigated polymorphism and the effect of infertility treatment. M235T polymorphism of the AGT gene seems unrelated to the development or the clinical course of en-dometriosis. No prognostic value has been found of the investigated polymorphism in predicting the effects of infertility treatment in women with endometriosis.

  17. Genetic polymorphism of estrogen receptor alpha gene in Egyptian women with type II diabetes mellitus

    PubMed Central

    Motawi, Tarek M.K.; El-Rehany, Mahmoud A.; Rizk, Sherine M.; Ramzy, Maggie M.; el-Roby, Doaa M.

    2015-01-01

    Estrogen might play an important role in type 2 diabetes mellitus pathogenesis. A number of polymorphisms have been reported in the estrogen receptor alpha gene including the XbaI and PvuII restriction enzyme polymorphisms. The aim of this study was to determine if ESRα gene polymorphisms are associated with type 2 diabetes mellitus and correlated with lipid profile. Ninety diabetic Egyptian patients were compared with forty healthy controls. ESRα genotyping of PvuII and XbaI was performed using restriction fragment length polymorphism analysis. Our study showed that there is more significant difference in the frequency of C and G polymorphic allele between patients and control groups in PvuII and XbaI respectively. Also carriers of minor C and G alleles of PvuII and XbaI gene polymorphisms were associated with increased fasting blood glucose and disturbance in lipid profile as there is an increase in total cholesterol, triglycerides and Low density lipoprotein. So findings of present study suggest the possibility that PvuII and XbaI polymorphisms in ERα are related to T2DM and with increased serum lipids among Egyptian population. PMID:26401488

  18. Gene-environment interaction between adiponectin gene polymorphisms and environmental factors on the risk of diabetic retinopathy.

    PubMed

    Li, Yuan; Wu, Qun Hong; Jiao, Ming Li; Fan, Xiao Hong; Hu, Quan; Hao, Yan Hua; Liu, Ruo Hong; Zhang, Wei; Cui, Yu; Han, Li Yuan

    2015-01-01

    To evaluate whether the adiponectin gene is associated with diabetic retinopathy (DR) risk and interaction with environmental factors modifies the DR risk, and to investigate the relationship between serum adiponectin levels and DR. Four adiponectin polymorphisms were evaluated in 372 DR cases and 145 controls. Differences in environmental factors between cases and controls were evaluated by unconditional logistic regression analysis. The model-free multifactor dimensionality reduction method and traditional multiple regression models were applied to explore interactions between the polymorphisms and environmental factors. Using the Bonferroni method, we found no significant associations between four adiponectin polymorphisms and DR susceptibility. Multivariate logistic regression found that physical activity played a protective role in the progress of DR, whereas family history of diabetes (odds ratio 1.75) and insulin therapy (odds ratio 1.78) were associated with an increased risk for DR. The interaction between the C-11377 G (rs266729) polymorphism and insulin therapy might be associated with DR risk. Family history of diabetes combined with insulin therapy also increased the risk of DR. No adiponectin gene polymorphisms influenced the serum adiponectin levels. Serum adiponectin levels did not differ between the DR group and non-DR group. No significant association was identified between four adiponectin polymorphisms and DR susceptibility after stringent Bonferroni correction. The interaction between C-11377G (rs266729) polymorphism and insulin therapy, as well as the interaction between family history of diabetes and insulin therapy, might be associated with DR susceptibility.

  19. Tumor Necrosis Factor-Alpha Gene Promoter Region Polymorphism and the Risk of Coronary Heart Disease

    PubMed Central

    Asifa, Gul Zareen; Kazmi, Syed Ali Raza; Javed, Qamar

    2013-01-01

    Background. Tumor necrosis factor-alpha (TNF-α) gene polymorphisms have been implicated in the manifestation of atherosclerosis. Controversy exists regarding the link between the cytokine's variant genotype and CHD among different ethnic groups. There have been fewer studies on the TNF-α gene −1031T>C and −863C>A polymorphisms in relation to CHD. Therefore, the current study was designed to investigate the association of the TNF-α gene −1031T>C and −863C>A polymorphisms with CHD in a Pakistani population. Methods. Patients with CHD (n = 310) and healthy individuals (n = 310) were enrolled in this study. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results. A significant difference was observed in the −863C>A polymorphism between patients with CHD and control subjects (P < 0.0001). CHD risk was positively associated with the variant allele −863A (P < 0.0001) in the study subjects. There was no significant link between the −1031T>C polymorphism and CHD risk in the study population. Haplotypes A-T and A-C of the TNF-alpha gene loci at −863 and −1031 showed higher frequency in the patient group compared with controls (P < 0.05). Conclusion. The TNF-α  −863C>A gene polymorphism was associated with the pathogenesis of CHD while the −1031T>C polymorphism did not show any link with the disease in a Pakistani population. PMID:24381514

  20. Polymorphism analysis of prion protein gene in 11 Pakistani goat breeds

    PubMed Central

    Hassan, Mohammad Farooque; Khan, Sher Hayat; Babar, Masroor Ellahi; Yang, Lifeng; Ali, Tariq; Khan, Jamal Muhammad; Shah, Syed Zahid Ali; Zhou, Xiangmei; Hussain, Tanveer; Zhu, Ting; Hussain, Tariq; Zhao, Deming

    2016-01-01

    ABSTRACT The association between caprine PrP gene polymorphisms and its susceptibility to scrapie has been investigated in current years. As the ORF of the PrP gene is extremely erratic in different breeds of goats, we studied the PrP gene polymorphisms in 80 goats which belong to 11 Pakistani indigenous goat breeds from all provinces of Pakistan. A total of 6 distinct polymorphic sites (one novel) with amino acid substitutions were identified in the PrP gene which includes 126 (A -> G), 304 (G -> T), 379 (A -> G), 414 (C -> T), 428 (A -> G) and 718 (C -> T). The locus c.428 was found highly polymorphic in all breeds as compare to other loci. On the basis of these PrP variants NJ phylogenetic tree was constructed through MEGA6.1 which showed that all goat breeds along with domestic sheep and Mauflon sheep appeared as in one clade and sharing its most recent common ancestors (MRCA) with deer species while Protein analysis has shown that these polymorphisms can lead to varied primary, secondary and tertiary structure of protein. Based on these polymorphic variants, genetic distance, multidimensional scaling plot and principal component analyses revealed the clear picture regarding greater number of substitutions in cattle PrP regions as compared to the small ruminant species. In particular these findings may pinpoint the fundamental control over the scrapie in Capra hircus on genetic basis. PMID:27388702

  1. 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.

  2. [CCR5, CCR2, apoe, p53, ITGB3 and HFE gene polymorphism in Western Siberia long-livers].

    PubMed

    Ivanoshchuk, D E; Mikhaĭlova, S V; Kulikov, I V; Maksimov, V N; Voevoda, M I; Romashchenko, A G

    2012-01-01

    In order to estimate the distribution of some polymorphisms for the CCR5, CCR2, apoE, p53, ITGB3, and HFE genes in Russian long-livers from Western Siberia, a sample of 271 individuals (range 90-105 years) was examined. It was demonstrated that carriage of the delta32 polymorphism for the CCR5 gene, V64/polymorphism for the CCR2 gene, e2/e3/e4 for the apoE gene, L33P for the ITGB3 gene, as well as H63D and S65C polymorphisms for the HFE gene does not influence on predisposition to the longevity; carriage of the 282 Y allele for the HFE gene negatively influences on the longevity; carriage of the heterozygous genotype for the R72P polymorphism for the p53 gene correlates with the longevity of elderly people.

  3. Reward dependence is related to norepinephrine transporter T-182C gene polymorphism in a Korean population.

    PubMed

    Ham, Byung-Joo; Choi, Myoung-Jin; Lee, Heon-Jeong; Kang, Rhee-Hun; Lee, Min-Soo

    2005-06-01

    It is well established that approximately 50% of the variance in personality traits is genetic. The goal of this study was to investigate a relationship between personality traits and the T-182C polymorphism in the norepinephrine transporter gene. The participants included 115 healthy adults with no history of psychiatric disorders and other physical illness during the past 6 months. All participants were tested with the Temperament and Character Inventory and genotyped norepinephrine transporter gene polymorphism. Differences on the Temperament and Character Inventory dimensions among three groups were examined with one-way analysis of variance. Our study suggests that the norepinephrine transporter T-182C gene polymorphism is associated with reward dependence in Koreans, but the small number of study participants and their sex and age heterogeneity limits generalization of our results. Further studies are necessary with a larger number of homogeneous participants to confirm whether the norepinephrine transporter gene is related to personality traits.

  4. The first report of prion-related protein gene (PRNT) polymorphisms in goat.

    PubMed

    Kim, Yong-Chan; Jeong, Byung-Hoon

    2017-06-01

    Prion protein is encoded by the prion protein gene (PRNP). Polymorphisms of several members of the prion gene family have shown association with prion diseases in several species. Recent studies on a novel member of the prion gene family in rams have shown that prion-related protein gene (PRNT) has a linkage with codon 26 of prion-like protein (PRND). In a previous study, codon 26 polymorphism of PRND has shown connection with PRNP haplotype which is strongly associated with scrapie vulnerability. In addition, the genotype of a single nucleotide polymorphism (SNP) at codon 26 of PRND is related to fertilisation capacity. These findings necessitate studies on the SNP of PRNT gene which is connected with PRND. In goat, several polymorphism studies have been performed for PRNP, PRND, and shadow of prion protein gene (SPRN). However, polymorphism on PRNT has not been reported. Hence, the objective of this study was to determine the genotype and allelic distribution of SNPs of PRNT in 238 Korean native goats and compare PRNT DNA sequences between Korean native goats and several ruminant species. A total of five SNPs, including PRNT c.-114G > T, PRNT c.-58A > G in the upstream of PRNT gene, PRNT c.71C > T (p.Ala24Val) and PRNT c.102G > A in the open reading frame (ORF) and c.321C > T in the downstream of PRNT gene, were found in this study. All five SNPs of caprine PRNT gene in Korean native goat are in complete linkage disequilibrium (LD) with a D' value of 1.0. Interestingly, comparative sequence analysis of the PRNT gene revealed five mismatches between DNA sequences of Korean native goats and those of goats deposited in the GenBank. Korean native black goats also showed 5 mismatches in PRNT ORF with cattle. To the best of our knowledge, this is the first genetic research of the PRNT gene in goat.

  5. Methylenetetrahydrofolate Reductase Gene Polymorphisms in Children with Attention Deficit Hyperactivity Disorder

    PubMed Central

    Gokcen, Cem; Kocak, Nadir; Pekgor, Ahmet

    2011-01-01

    Objective: The purpose of this study was to evaluate the relationship between 5,10- methylenetetrahydrofolate reductase (MTHFR) polymorphisms and Attention Deficit Hyperactivity Disorder (ADHD) in a sample of Turkish children. Study Design: MTHFR gene polymorphisms were assessed in 40 patients with ADHD and 30 healty controls. Two mutations in the MTHFR gene were investigated using polymerase chain reactions and restriction fragment length polymorphisms. Results: Although there were no statistically significant differences in genotype distributions of the C677T alleles between the ADHD and the control groups (p=0,678) but the genotypic pattern of the distributions of the A1298C alleles was different between the ADHD patients and the controls (p=0,033). Conclusions: Preliminary data imply a possible relationship between A1298C MTHFR polymorphisms and the ADHD. PMID:21897766

  6. Functional polymorphisms in the sigma1 receptor gene associated with alcoholism.

    PubMed

    Miyatake, Ryosuke; Furukawa, Aizo; Matsushita, Sachio; Higuchi, Susumu; Suwaki, Hiroshi

    2004-01-01

    Sigma1 receptors are involved in the pathogenesis of drug abuse. Two polymorphisms (GC-241-240TT and Gln2Pro) in the sigma1 receptor gene (SIGMAR1) have been identified. To investigate the role of SIGMAR1 in conveying susceptibility to alcoholism, we performed a functional analysis of polymorphisms in the SIGMAR1 and a case-control study. We initially screened for polymorphisms in the 5'-upstream region. The effects of the polymorphisms on transcriptional activity were determined using a gene reporter assay. The distribution of SIGMAR1 polymorphisms was analyzed in 307 alcoholic and 302 control subjects. A novel T-485A polymorphism was identified. The transcriptional activity of the A-485 allele and the TT-241-240 allele was significantly reduced compared with that of the T-485 allele and the GC-241-240 allele. The frequencies of the A-485 allele (chi2=5.575, df=1, p=.0205) and the TT-241-240/Pro2 haplotype (chi2=21.464, df=1, p<.0001) were significantly higher in control subjects compared with alcoholic subjects. The T-485A and the GC-241-240TT may be functional polymorphisms, and the A-485 allele and TT-241-240/Pro2 haplotype are possible protective factors for the development of alcoholism.

  7. Dopamine D4 receptor gene polymorphism and personality traits in healthy volunteers.

    PubMed

    Persson, M L; Wasserman, D; Geijer, T; Frisch, A; Rockah, R; Michaelovsky, E; Apter, A; Weizman, A; Jönsson, E G; Bergman, H

    2000-01-01

    An association between long alleles of a variable number tandem repeat (VNTR) polymorphism in the dopamine receptor D4 gene and the extraversion related personality traits Excitement and Novelty Seeking has been reported in healthy subjects. In an attempt to replicate the previous findings, 256 healthy Caucasian volunteers were analysed for a potential relationship between the dopamine receptor D4 exon III VNTR polymorphism and Extraversion as assessed by the Revised Neo Personality Inventory (NEO PI-R). The present study did not yield evidence for an association between Extraversion and the dopamine receptor D4 polymorphism.

  8. Mismatch repair gene MSH3 polymorphism is associated with the risk of sporadic prostate cancer.

    PubMed

    Hirata, Hiroshi; Hinoda, Yuji; Kawamoto, Ken; Kikuno, Nobuyuki; Suehiro, Yutaka; Okayama, Naoko; Tanaka, Yuichiro; Dahiya, Rajvir

    2008-05-01

    The mismatch repair system is a DNA repair mechanism that corrects mispaired bases during DNA replication errors. Cancer cells deficient in MMR proteins have a 10(2) to 10(3)-fold increase in the mutation rate. Single nucleotide polymorphisms of mismatch repair genes have been shown to cause a decrease in DNA repair activity. We hypothesized that mismatch repair gene polymorphism could be a risk factor for prostate cancer and p53 Pro/Pro genotype carriers could influence MSH3 and MSH6 polymorphisms. DNA samples from 110 patients with prostate cancer and 110 healthy controls were analyzed by single strand conformational polymorphism and polymerase chain reaction-restriction fragment length polymorphism to determine the genotypic frequency of 5 polymorphic loci on 2 MMR genes (MSH3 and MSH6) and p53 codon72. The chi-square test was applied to compare genotype frequency between patients and controls. A significant increase in the G/A+A/A genotype of MSH3 Pro222Pro was observed in patients compared to controls (OR 1.87, 95% CI 1.0-3.5). The frequency of A/G + G/G genotypes of MSH3 exon23 Thr1036Ala also tended to increase in patients (OR 1.57, 95% CI 0.92-2.72). In p53 codon72 Arg/Pro + Pro/Pro carriers the frequency of the AG + GG genotype of MSH3 exon23 was significantly increased in patients compared to controls (OR 2.1, 95% CI 1.05-4.34). To our knowledge this is the first report of the association of MSH3 gene polymorphisms in prostate cancer. These results suggest that the MSH3 polymorphism may be a risk factor for prostate cancer.

  9. Polymorphisms and linkage analysis for ICAM-1 and the selectin gene cluster

    SciTech Connect

    Vora, D.K.; Rosenbloom, C.L.; Cottingham, R.W.

    1994-06-01

    Genetic polymorphisms in leukocyte and endothelial cell adhesion molecules may be important variables with regard to susceptibility to multifactorial disease processes that include an inflammatory component. For this reason, polymorphisms were sought for intercellular adhesion molecule-1 (ICAM-1; gene symbol ICAM1) and for the three genes in the selectin cluster, P-selectin, L-selectin, and E-selectin (gene symbols SELP, SELL, and SELE, respectively). Two amino acid polymorphisms were identified for ICAM-1; Gly or Arg at codon 241 and Lys or Glu at codon 469. Dinucleotide repeat polymorphisms were identified in the 3{prime}-untranslated region for ICAM-1 and in intron 9 for P-selectin. Restriction fragmentmore » length polymorphisms were found using cDNAs for each of the three selectin genes as probes; E-selectin with BglII, P-selectin with ScaI, and L-selectin with HincII. Linkage analysis was performed for the selectin gene cluster and for ICAM-1 using the CEPH families; ICAM-1 is very tightly linked to the LDL receptor on chromosome 19, and the selectin cluster is linked to markers at chromosome 1q23. 41 refs., 2 tabs.« less

  10. Association of I-FABP gene polymorphism and the risk of coronary heart disease.

    PubMed

    Yuan, Dong; Yu, Changqing; Zeng, Chunyu

    2015-01-01

    The study aimed to investigate the association between polymorphism of I-FABP gene and coronary heart disease (CHD). 225 patients with CHD were randomly recruited into the case group, and 196 healthy elderly volunteers were recruited from Medical Examination Center of our hospital as control. General clinical data were collected and plasma TC, TG, LDL-C, HDL-C levels were measured. Besides, polymerase chain reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) technology were used to detect the polymorphism of Hha-I enzyme cleavage sites in I-FABP gene in the study population. Hha-I cleavage sites occurred at codon 54 in exon in the coding sequencing of I-FABP gene in all participants. After cleavage with Hha-I enzyme, the genotypes were identified as wild-type A/A, heterozygous mutant A/T and homozygous mutant T/T. In case group, A/T and T/T genetic carriers had significantly higher levels of TC, TG and LDL-C than A/A carriers (P<0.05). However, in control group, similar differences were not observed (P>0.05). BMI, dietary habits and I-FABP alleles were independent risk factors of CHD. The polymorphism of I-FABP gene existed in the study population. And this genetic variation had influence on lipid metabolism, which was associated with the risk of developing CHD. I-FABP gene polymorphism may contribute to the increased genetic susceptibility to CHD.

  11. 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

  12. 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.

  13. Apolipoprotein gene polymorphisms and plasma levels in healthy Tunisians and patients with coronary artery disease

    PubMed Central

    Bahri, Raoudha; Esteban, Esther; Moral, Pedro; Hassine, Mohsen; Hamda, Khaldoun Ben; Chaabani, Hassen

    2008-01-01

    Aim To analyze apolipoprotein gene polymorphisms in the Tunisian population and to check the relation of these polymorphisms and homocysteine, lipid and apolipoprotein levels to the coronary artery disease (CAD). Methods In healthy blood donors and in patients with CAD complicated by myocardial infarction (MI) four apolipoprotein gene polymorphisms [APO (a) PNR, APO E, APO CI and APO CII] were determined and plasma levels of total homocysteine, total cholesterol (TC), triglycerides (TG), HDL-cholesterol (HLD-C) and apolipoproteins (apo A-I, Apo B, Apo E) were measured. Results Analysis of the four apolipoprotein gene polymorphisms shows a relative genetic homogeneity between Tunisian population and those on the other side of Mediterranean basin. Compared to controls, CAD patients have significantly higher main concentrations of TC, TG, LDL-C, apo B and homocysteine, and significantly lower ones of HDL-C, apo A-I and apo E. The four apolipoprotein gene polymorphisms have not showed any significant differences between patients and controls. However, the APO E4 allele appears to be associated to the severity of CAD and to high levels of atherogenic parameters and low level of apo E, which has very likely an anti-atherogenic role. Conclusion Although APO (a) PNR, APO CI and APO CII genes are analyzed in only few populations, they show a frequency distribution, which is not at variance with that of APO E gene and other widely studied genetic markers. In the Tunisian population the APO E 4 appears to be only indirectly involved in the severity of CAD. In the routine practice, in addition of classic parameters, it will be useful to measure the concentration of apo E and that of Homocysteine and if possible to determine the APO E gene polymorphism. PMID:19014618

  14. Relationship of interleukin-1B gene promoter region polymorphism with Helicobacter pylori infection and gastritis.

    PubMed

    Ramis, Ivy Bastos; Vianna, Júlia Silveira; Halicki, Priscila Cristina Bartolomeu; Lara, Caroline; Tadiotto, Thássia Fernanda; da Silva Maciel, João Batista; Gonçalves, Carla Vitola; von Groll, Andrea; Dellagostin, Odir Antônio; da Silva, Pedro Eduardo Almeida

    2015-09-29

    Helicobacter pylori infection is associated with gastritis, peptic ulcer disease and gastric carcinoma. The severity of damage is determined by the interplay between environmental/behavioral factors, bacterial pathogenicity genes and host genetic polymorphisms that can influence the secretion levels of inflammatory cytokines. Accordingly, this study aimed to identify polymorphisms in the IL-1B and IL-1RN genes and their associations with H. pylori infection, cagA gene of H. pylori, and gastroduodenal diseases. Gastric biopsy samples from 151 patients infected with H. pylori and 76 uninfected individuals were analyzed. H. pylori infection was diagnosed by histology and PCR. Polymorphisms at positions -511, -31 and +3954 of the IL-1B gene were detected by PCR-RFLP, and an analysis of the VNTR polymorphism of the IL-1RN gene was performed by PCR. It was observed that the presence of the T/T genotype at position -511 and the C/C genotype at position -31 were associated with H. pylori infection and with an increased risk of gastritis in H. pylori-positive patients. Additionally, strains from patients H. pylori-positive carrying the cagA gene was significantly related with the T/T genotype at position -511 of IL-1B.  No association of polymorphisms at position +3954 of IL-1B and in the IL-1RN with H. pylori infection and with risk of severe gastric diseases was found. We demonstrated that polymorphisms in the promoter region of the IL-1B gene (at positions -511 and -31) are associated with an enhanced risk of H. pylori infection as well as gastritis in H. pylori-positive patients.

  15. Extensive shared polymorphism at non-MHC immune genes in recently diverged North American prairie grouse

    USGS Publications Warehouse

    Minias, Piotr; Bateson, Zachary W.; Whittingham, Linda A.; Johnson, Jeff A.; Oyler-McCance, Sara J.; Dunn, Peter O.

    2018-01-01

    Gene polymorphisms shared between recently diverged species are thought to be widespread and most commonly reflect introgression from hybridization or retention of ancestral polymorphism through incomplete lineage sorting. Shared genetic diversity resulting from incomplete lineage sorting is usually maintained for a relatively short period of time, but under strong balancing selection it may persist for millions of years beyond species divergence (balanced trans-species polymorphism), as in the case of the major histocompatibility complex (MHC) genes. However, balancing selection is much less likely to act on non-MHC immune genes. The aim of this study was to investigate the patterns of shared polymorphism and selection at non-MHC immune genes in five grouse species from Centrocercus and Tympanuchus genera. For this purpose, we genotyped five non-MHC immune genes that do not interact directly with pathogens, but are involved in signaling and regulate immune cell growth. In contrast to previous studies with MHC, we found no evidence for balancing selection or balanced trans-species polymorphism among the non-MHC immune genes. No haplotypes were shared between genera and in most cases more similar allelic variants sorted by genus. Between species within genera, however, we found extensive shared polymorphism, which was most likely attributable to introgression or incomplete lineage sorting following recent divergence and large ancestral effective population size (i.e., weak genetic drift). Our study suggests that North American prairie grouse may have attained relatively low degree of reciprocal monophyly at nuclear loci and reinforces the rarity of balancing selection in non-MHC immune genes.

  16. Association between polymorphisms in prostanoid receptor genes and aspirin-intolerant asthma.

    PubMed

    Kim, Sang-Heon; Kim, Yoon-Keun; Park, Heung-Woo; Jee, Young-Koo; Kim, Sang-Hoon; Bahn, Joon-Woo; Chang, Yoon-Seok; Kim, Seung-Hyun; Ye, Young-Min; Shin, Eun-Soon; Lee, Jong-Eun; Park, Hae-Sim; Min, Kyung-Up

    2007-04-01

    Genetic predisposition is linked to the pathogenesis of aspirin-intolerant asthma. Most candidate gene approaches have focused on leukotriene-related pathways, whereas there have been relatively few studies evaluating the effects of polymorphisms in prostanoid receptor genes on the development of aspirin-intolerant asthma. Therefore, we investigated the potential association between prostanoid receptor gene polymorphisms and the aspirin-intolerant asthma phenotype. We screened for genetic variations in the prostanoid receptor genes PTGER1, PTGER2, PTGER3, PTGER4, PTGDR, PTGIR, PTGFR, and TBXA2R using direct sequencing, and selected 32 tagging single nucleotide polymorphisms among the 77 polymorphisms with frequencies >0.02 based on linkage disequilibrium for genotyping. We compared the genotype distributions and allele frequencies of three participant groups (108 patients with aspirin-intolerant asthma, 93 patients with aspirin-tolerant asthma, and 140 normal controls). Through association analyses studies of the 32 single nucleotide polymorphisms, the following single nucleotide polymorphisms were found to have significant associations with the aspirin-intolerant asthma phenotype: -616C>G (P=0.038) and -166G>A (P=0.023) in PTGER2; -1709T>A (P=0.043) in PTGER3; -1254A>G (P=0.018) in PTGER4; 1915T>C (P=0.015) in PTGIR; and -4684C>T (P=0.027), and 795T>C (P=0.032) in TBXA2R. In the haplotype analysis of each gene, the frequency of PTGIR ht3[G-G-C-C], which includes 1915T>C, differed significantly between the aspirin-intolerant asthma patients and aspirin-tolerant asthma patients (P=0.015). These findings suggest that genetic polymorphisms in PTGER2, PTGER3, PTGER4, PTGIR, and TBXA2R play important roles in the pathogenesis of aspirin-intolerant asthma.

  17. Thrombophilic gene polymorphisms and recurrent pregnancy loss in Greek women.

    PubMed

    Chatzidimitriou, M; Chatzidimitriou, D; Mavridou, M; Anetakis, C; Chatzopoulou, F; Lialiaris, T; Mitka, S

    2017-12-01

    Recurrent pregnancy loss (RPL) is a multifactorial disorder. The aim of this study was the detection of various genetic polymorphisms and their correlation to RPL, in Greek women. The impact of 12 thrombophilic polymorphisms was evaluated, among 48 Greek women with a history of RPL, vs 27 healthy parous women. Multiplex PCR and in situ hybridization on nitrocellulose films were performed, to investigate 12 genetic polymorphisms previously reported as risk factors for RPL. Heterozygous FV Leiden, homozygous PAI-1 4G/4G, heterozygous MTHFR C677T, homozygous MTHFR A1298C, as much as the combined thrombophilic genotypes MTHFR 677T + ACE Ι/D, MTHFR 677T/1298C + ACE D/D, ACE I/D + b-fibrinogen -455 G/A, FV HR2 + b-fibrinogen -455 G/A showed a correlation as risk factors for RPL, whereas the rest of the investigated polymorphisms and their combinations did not render statistically significant differences between the two groups in study. The results of this study, as well as those of similar studies, concerning the detection of genetic, environmental, and physiological factors underlying RPL, will prove of critical significance in the investigation and treatment of thrombophilic predisposition, in cases of RPL. © 2017 John Wiley & Sons Ltd.

  18. Canine olfactory receptor gene polymorphism and its relation to odor detection performance by sniffer dogs.

    PubMed

    Lesniak, Anna; Walczak, Marta; Jezierski, Tadeusz; Sacharczuk, Mariusz; Gawkowski, Maciej; Jaszczak, Kazimierz

    2008-01-01

    The outstanding sensitivity of the canine olfactory system has been acknowledged by using sniffer dogs in military and civilian service for detection of a variety of odors. It is hypothesized that the canine olfactory ability is determined by polymorphisms in olfactory receptor (OR) genes. We investigated 5 OR genes for polymorphic sites which might affect the olfactory ability of service dogs in different fields of specific substance detection. All investigated OR DNA sequences proved to have allelic variants, the majority of which lead to protein sequence alteration. Homozygous individuals at 2 gene loci significantly differed in their detection skills from other genotypes. This suggests a role of specific alleles in odor detection and a linkage between single-nucleotide polymorphism and odor recognition efficiency.

  19. Molecular basis of length polymorphism in the human zeta-globin gene complex.

    PubMed Central

    Goodbourn, S E; Higgs, D R; Clegg, J B; Weatherall, D J

    1983-01-01

    The length polymorphism between the human zeta-globin gene and its pseudogene is caused by an allele-specific variation in the copy number of a tandemly repeating 36-base-pair sequence. This sequence is related to a tandemly repeated 14-base-pair sequence in the 5' flanking region of the human insulin gene, which is known to cause length polymorphism, and to a repetitive sequence in intervening sequence (IVS) 1 of the pseudo-zeta-globin gene. Evidence is presented that the latter is also of variable length, probably because of differences in the copy number of the tandem repeat. The homology between the three length polymorphisms may be an indication of the presence of a more widespread group of related sequences in the human genome, which might be useful for generalized linkage studies. PMID:6308667

  20. Association of Gene Polymorphisms in Interleukin 6 in Infantile Bronchial Asthma.

    PubMed

    Babusikova, Eva; Jurecekova, Jana; Jesenak, Milos; Evinova, Andrea

    2017-07-01

    The genetic background of bronchial asthma is complex, and it is likely that multiple genes contribute to its development both directly and through gene-gene interactions. Cytokines contribute to different aspects of asthma, as they determine the type, severity and outcomes of asthma pathogenesis. Allergic asthmatics undergoing an asthmatic attack exhibit significantly higher levels of pro-inflammatory cytokines, such as interleukins and chemokines. In recent years, cytokines and their receptors have been shown to be highly polymorphic, and this prompted us to investigate interleukin 6 promoter polymorphisms at position -174G/C (rs1800795) and at -572G/C (rs1800796) in relation to asthma in children. Interleukin 6 promoter polymorphisms were analyzed in bronchial asthma patients and healthy children using polymerase chain reaction-restriction fragment length polymorphism analysis. We observed a significant association between polymorphism at -174G/C and bronchial asthma (OR=3.4, 95% CI: 2.045-5.638, P<.001). Higher associations between polymorphism at IL-6 -174G/C and bronchial asthma were observed in atopic patients (OR=4.1, 95% CI: 2.308-7.280, P<8.10 -7 ). Interleukin 6 polymorphism is associated with bronchial asthma, particularly its atopic phenotype. Expression and secretion of interleukins in asthmatic patients may be affected by genetic polymorphisms, and could have a disease-modifying effect in the asthmatic airway and modify the therapeutic response. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Antioxidant-related gene polymorphisms associated with the cardio-ankle vascular index in young Russians.

    PubMed

    Sorokin, Alexander V; Kotani, Kazuhiko; Bushueva, Olga Y; Polonikov, Alexey V

    2016-04-01

    The cardio-ankle vascular index is a measure of arterial stiffness, whereas oxidative stress underlies arterial pathology. This study aimed to investigate the association between the cardio-ankle vascular index and antioxidant-related gene polymorphisms in young Russians. A total of 89 patients (mean age, 21.6 years) were examined by the cardio-ankle vascular index and for 15 gene polymorphisms related to antioxidant enzymes including FMO3 (flavin-containing monooxygenase 3), GPX1 (glutathione peroxidase 1), and GPX4 (glutathione peroxidase 4). A higher cardio-ankle vascular index level was detected in carriers with the KK-genotype of FMO3 polymorphism rs2266782 than in those without (mean levels: 6.2 versus 5.6, respectively, p<0.05). Similarly, a higher cardio-ankle vascular index level was seen in carriers with the CC-genotype of GPX4 polymorphism rs713041 than in those without (6.0 versus 5.5, respectively, p<0.05). We did not observe significant associations between the cardio-ankle vascular index levels and the other gene polymorphisms. Although carriers with the LL-genotype of GPX1 polymorphism rs1050450 showed a higher diastolic blood pressure level than those without, the polymorphism did not affect the cardio-ankle vascular index level. This study showed a significant association between rs2266782 and rs713041 polymorphisms and arterial stiffness, as measured by the cardio-ankle vascular index, in young Russians. The pathways utilised by antioxidant enzymes may be responsible for early arterial stiffening in the Russian population.

  2. A common polymorphism of the MCT1 gene and athletic performance.

    PubMed

    Fedotovskaya, Olga N; Mustafina, Leysan J; Popov, Daniil V; Vinogradova, Olga L; Ahmetov, Ildus I

    2014-01-01

    In red skeletal muscle, monocarboxylate transporter 1 (MCT1) is required for lactate to enter the myocytes for oxidation. The A1470T polymorphism (rs1049434) in the MCT1 gene was shown to be associated with lactate transport rates in human skeletal muscles. The aim of the study was to compare genotype and allele frequencies of the MCT1 gene polymorphism in 323 Russian athletes and 467 nonathletic controls and to investigate the association of the MCT1 gene A1470T polymorphism with maximal oxygen consumption and maximal lactate concentration in rowers (n = 79). Genotyping for the A1470T MCT1 polymorphism was performed by PCR-RFLP method. Physiological measurements of 79 Russian rowers of national competitive standard were determined during an incremental test to exhaustion on a rowing ergometer. Frequencies of the A allele (71.8% vs 62.5%, P < .0001) and AA genotype (59.8% vs 39.4%, P < .0001) were significantly higher in endurance-oriented athletes (n = 142) than in the control group. Mean blood lactate concentration was higher in male rowers with the T allele (AT+TT 10.26 ± 1.89 mmol/L, AA 8.75 ± 1.69 mmol/L, P = .005). MCT1 gene A1470T polymorphism is associated with endurance athlete status and blood lactate level after intensive exercise.

  3. Association of interleukin-10 gene polymorphisms with breast cancer in a Chinese population.

    PubMed

    Kong, Fanjun; Liu, Jie; Liu, Yongheng; Song, Bao; Wang, Hualing; Liu, Wenchao

    2010-06-17

    Interleukin-10(IL-10) is a multifunctional cytokine with both immunosuppressive and antiangiogenic functions. Polymorphisms in the IL-10 gene promoter genetically determine interindividual differences in IL-10 production. This study was performed to determined whether polymorphisms in the IL-10 gene promoter were associated with breast cancer in a Chinese Han population. We genotyped 315 patients with breast cancer and 322 healthy control subjects for -1082A/G, -819T/C and -592A/C single nucleotide polymorphisms in the promoter region of the IL-10 gene by polymerase chain reactionerestriction fragment length polymorphism (PCR-RFLP). There were no significant differences in genotype, allele, or haplotype frequencies in all three loci between patients and healthy controls. Analysis of breast cancer prognostic and predictive factors revealed that the -1082AA genotype was associated with a significantly increased risk of lymph node (LN) involvement (P = 0.041) and larger tumor size (P = 0.039) at the time of diagnosis. Furthermore, in the haplotype analysis of IL-10 gene, we found that patients carrying ATA haplotype were in higher LN involvement (p = 0.022) and higher tumor stage(p = 0.028) of breast cancer at the time of diagnosis compared with others. Our findings suggest that IL-10 promoter polymorphisms participate in the progression of breast cancer rather than in its initial development in Chinese Han women.

  4. Associations of SAA1 gene polymorphism with lipid lelvels and osteoporosis in Chinese women.

    PubMed

    Feng, Zheng-Ping; Li, Xiao-Yu; Jiang, Rong; Deng, Hua-Cong; Yang, Mei; Zhou, Qin; Que, Wen-Jun; Du, Jia

    2013-03-22

    The development of osteoporosis is associated with several risk factors, such as genetic polymorphisms and enviromental factors. This study assessed the correlation between SAA1 gene rs12218 polymorphism and HDL-C lelvels and osteoporosis in a population of Chinese women. A total of 387 postmenopausal female patients who were diagnosed with osteoporosis (case group) based on bone mineral density measurements via dual-energy x-ray absorptiometry and 307 females with no osteoporosis (control group) were included in this study. Correlations between SAA1 gene rs12218 polymorphism and osteoporosis and HDL-C level were investigated through the identification of SAA1 gene rs12218 polymorphism genotypes using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The TT genotype of rs12218 was more frequently in osteoporosis patients than in control subjects (P <0.001). And the rs12218 was found to be associated with plasma TG, HDL-C, LDL-C, and BMD levels in osteoporosis patients (P<0.05). The present results indicate that both osteoporosis and lipids levels are associated with the TT genotype of rs12218 in the human SAA1 gene.

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

    PubMed

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

    2018-05-11

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

  6. [Association of IL-1β-511T gene rs16944 polymorphism with febrile seizures].

    PubMed

    Ren, Xiao-Tun; Sun, Su-Zhen; Liu, Fang; Wang, Xiao-Ming

    2014-02-01

    Despite substantial research efforts worldwide, the role of inflammatory cytokine IL-1β in the onset of febrile seizures (FS) remains controversial. The aim of this study was to assess the relationship between rs16944 polymorphism of the IL-1β-511T gene and occurrence of simple FS in a sample of Han children in northern China. The IL-1β-511T gene rs16944 was genotyped by SNaPshot SNP technique in 141 FS children and 130 healthy control subjects. The genotypic and allelic frequencies in the two groups were comparatively analyzed. There were no significant differences in genotypic and allelic frequencies of rs16944 polymorphism of the IL-1β-511T gene between FS patients and control subjects (P>0.05).When the clinical data on A/A, A/G and G/G genotypes of the rs16944 polymorphism in FS patients, there was statistically significant difference in age of first onset (χ(2)=19.491, P<0.01), temperature of first onset (χ(2)=9.317, P<0.05) and family history of FS (χ(2)=26.798, P<0.01). There is no association between rs16944 polymorphism of the IL-1β-511T gene and the incidence of FS in Han children in Northern China. However, the differences in genotypes of this polymorphism might be associated with pathogenesis and prognosis of simple FS in the population studied.

  7. Interleukin gene polymorphisms and breast cancer: a case control study and systematic literature review

    PubMed Central

    Balasubramanian, SP; Azmy, IAF; Higham, SE; Wilson, AG; Cross, SS; Cox, A; Brown, NJ; Reed, MW

    2006-01-01

    Background Interleukins and cytokines play an important role in the pathogenesis of many solid cancers. Several single nucleotide polymorphisms (SNPs) identified in cytokine genes are thought to influence the expression or function of these proteins and many have been evaluated for their role in inflammatory disease and cancer predisposition. The aim of this study was to evaluate any role of specific SNPs in the interleukin genes IL1A, IL1B, IL1RN, IL4R, IL6 and IL10 in predisposition to breast cancer susceptibility and severity. Methods Candidate single nucleotide polymorphisms (SNPs) in key cytokine genes were genotyped in breast cancer patients and in appropriate healthy volunteers who were similar in age, race and sex. Genotyping was performed using a high throughput allelic discrimination method. Data on clinico-pathological details and survival were collected. A systematic review of Medline English literature was done to retrieve previous studies of these polymorphisms in breast cancer. Results None of the polymorphisms studied showed any overall predisposition to breast cancer susceptibility, severity or to time to death or occurrence of distant metastases. The results of the systematic review are summarised. Conclusion Polymorphisms within key interleukin genes (IL1A, IL1B, IL1RN, IL4R, IL6 and IL10 do not appear to play a significant overall role in breast cancer susceptibility or severity. PMID:16842617

  8. Relationship between ADD1 Gly460Trp gene polymorphism and essential hypertension in Madeira Island.

    PubMed

    Sousa, Ana Célia; Palma Dos Reis, Roberto; Pereira, Andreia; Borges, Sofia; Freitas, Ana Isabel; Guerra, Graça; Góis, Teresa; Rodrigues, Mariana; Henriques, Eva; Freitas, Sónia; Ornelas, Ilídio; Pereira, Décio; Brehm, António; Mendonça, Maria Isabel

    2017-10-01

    Essential hypertension (EH) is a complex disease in which physiological, environmental, and genetic factors are involved in its genesis. The genetic variant of the alpha-adducin gene (ADD1) has been described as a risk factor for EH, but with controversial results.The objective of this study was to evaluate the association of ADD1 (Gly460Trp) gene polymorphism with the EH risk in a population from Madeira Island.A case-control study with 1614 individuals of Caucasian origin was performed, including 817 individuals with EH and 797 controls. Cases and controls were matched for sex and age, by frequency-matching method. All participants collected blood for biochemical and genotypic analysis for the Gly460Trp polymorphism. We further investigated which variables were independently associated to EH, and, consequently, analyzed their interactions.In our study, we found a significant association between the ADD1 gene polymorphism and EH (odds ratio 2.484, P = .01). This association remained statistically significant after the multivariate analysis (odds ratio 2.548, P = .02).The ADD1 Gly460Trp gene polymorphism is significantly and independently associated with EH risk in our population. The knowledge of genetic polymorphisms associated with EH is of paramount importance because it leads to a better understanding of the etiology and pathophysiology of this pathology.

  9. Relationship between ADD1 Gly460Trp gene polymorphism and essential hypertension in Madeira Island

    PubMed Central

    Sousa, Ana Célia; Palma dos Reis, Roberto; Pereira, Andreia; Borges, Sofia; Freitas, Ana Isabel; Guerra, Graça; Góis, Teresa; Rodrigues, Mariana; Henriques, Eva; Freitas, Sónia; Ornelas, Ilídio; Pereira, Décio; Brehm, António; Mendonça, Maria Isabel

    2017-01-01

    Abstract Essential hypertension (EH) is a complex disease in which physiological, environmental, and genetic factors are involved in its genesis. The genetic variant of the alpha-adducin gene (ADD1) has been described as a risk factor for EH, but with controversial results. The objective of this study was to evaluate the association of ADD1 (Gly460Trp) gene polymorphism with the EH risk in a population from Madeira Island. A case-control study with 1614 individuals of Caucasian origin was performed, including 817 individuals with EH and 797 controls. Cases and controls were matched for sex and age, by frequency-matching method. All participants collected blood for biochemical and genotypic analysis for the Gly460Trp polymorphism. We further investigated which variables were independently associated to EH, and, consequently, analyzed their interactions. In our study, we found a significant association between the ADD1 gene polymorphism and EH (odds ratio 2.484, P = .01). This association remained statistically significant after the multivariate analysis (odds ratio 2.548, P = .02). The ADD1 Gly460Trp gene polymorphism is significantly and independently associated with EH risk in our population. The knowledge of genetic polymorphisms associated with EH is of paramount importance because it leads to a better understanding of the etiology and pathophysiology of this pathology. PMID:29049185

  10. Associations of SAA1 gene polymorphism with Lipid lelvels and osteoporosis in Chinese women

    PubMed Central

    2013-01-01

    Background The development of osteoporosis is associated with several risk factors, such as genetic polymorphisms and enviromental factors. This study assessed the correlation between SAA1 gene rs12218 polymorphism and HDL-C lelvels and osteoporosis in a population of Chinese women. Methods A total of 387 postmenopausal female patients who were diagnosed with osteoporosis (case group) based on bone mineral density measurements via dual-energy x-ray absorptiometry and 307 females with no osteoporosis (control group) were included in this study. Correlations between SAA1 gene rs12218 polymorphism and osteoporosis and HDL-C level were investigated through the identification of SAA1 gene rs12218 polymorphism genotypes using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results The TT genotype of rs12218 was more frequently in osteoporosis patients than in control subjects (P <0.001). And the rs12218 was found to be associated with plasma TG, HDL-C, LDL-C, and BMD levels in osteoporosis patients (P<0.05). Conclusions The present results indicate that both osteoporosis and lipids levels are associated with the TT genotype of rs12218 in the human SAA1 gene. PMID:23522429

  11. [The value of 5-HTT gene polymorphism for the assessment and prediction of male adolescence violence].

    PubMed

    Yu, Yue; Liu, Xiang; Yang, Zhen-xing; Qiu, Chang-jian; Ma, Xiao-hong

    2012-08-01

    To establish an adolescent violence crime prediction model, and to assess the value of serotonin transporter (5-HTT) gene polymorphism for the assessment and prediction of violent crime. Investigative tools were used to analyze the difference in personality dimensions, social support, coping styles, aggressiveness, impulsivity, and family condition scale between 223 adolescents with violence behavior and 148 adolescents without violence behavior. The distribution of 5-HTT gene polymorphisms (5-HTTLPR and 5-HTTVNTR) was compared between the two groups. The role of 5-HTT gene polymorphism on adolescent personality, impulsion and aggression scale also was also analyzed. Stepwise logistic regression was used to establish a predictive model for adolescent violent crime. Significant difference was found between the violence group and the control group on multiple dimensions of psychology and environment scales. However, no statistical difference was found with regard to the 5-HTT genotypes and alleles between adolescents with violent behaviors and normal controls. The rate of prediction accuracy was not significantly improved when 5-HTT gene polymorphism was taken into the model. The violent crime of adolescents was closely related with social and environmental factors. No association was found between 5-HTT polymorphisms and adolescent violence criminal behavior.

  12. No Association between Personality and Candidate Gene Polymorphisms in a Wild Bird Population

    PubMed Central

    Durieux, Gillian; Burke, Terry; Dugdale, Hannah L.

    2015-01-01

    Consistency of between-individual differences in behaviour or personality is a phenomenon in populations that can have ecological consequences and evolutionary potential. One way that behaviour can evolve is to have a genetic basis. Identifying the molecular genetic basis of personality could therefore provide insight into how and why such variation is maintained, particularly in natural populations. Previously identified candidate genes for personality in birds include the dopamine receptor D4 (DRD4), and serotonin transporter (SERT). Studies of wild bird populations have shown that exploratory and bold behaviours are associated with polymorphisms in both DRD4 and SERT. Here we tested for polymorphisms in DRD4 and SERT in the Seychelles warbler (Acrocephalus sechellensis) population on Cousin Island, Seychelles, and then investigated correlations between personality and polymorphisms in these genes. We found no genetic variation in DRD4, but identified four polymorphisms in SERT that clustered into five haplotypes. There was no correlation between bold or exploratory behaviours and SERT polymorphisms/haplotypes. The null result was not due to lack of power, and indicates that there was no association between these behaviours and variation in the candidate genes tested in this population. These null findings provide important data to facilitate representative future meta-analyses on candidate personality genes. PMID:26473495

  13. 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.

  14. PERB11 (MIC): a polymorphic MHC gene is expressed in skin and single nucleotide polymorphisms are associated with psoriasis

    PubMed Central

    Tay, G K; Hui, J; Gaudieri, S; Schmitt-Egenolf, M; Martinez, O P; Leelayuwat, C; Williamson, J F; Eiermann, T H; Dawkins, R L

    2000-01-01

    The susceptibility genes for psoriasis remain to be identified. At least one of these must be in the major histocompatibility complex (MHC) to explain associations with alleles at human leucocyte antigen (HLA)-A, -B, -C, -DR, -DQ and C4. In fact, most of these alleles are components of just two ancestral haplotypes (AHs) designated 13.1 and 57.1. Although relevant MHC gene(s) could be within a region of at least 4 Mb, most studies have favoured the area near HLA-B and -C. This region contains a large number of non-HLA genes, many of which are duplicated and polymorphic. Members of one such gene family, PERB11.1 and PERB11.2, are expressed in the skin and are encoded in the region between tumour necrosis factor and HLA-B. To investigate the relationship of PERB11.1 alleles to psoriasis, sequence based typing was performed on 97 patients classified according to age of onset and family history. The frequency of the PERB11.1*06 allele is 44% in type I psoriasis but only 7% in controls (Pc = 0.003 by Fisher's exact test, two-tailed). The major determinant of this association is a single nucleotide polymorphism (SNP) within intron 4. In normal and affected skin, expression of PERB11 is mainly in the basal layer of the epidermis including ducts and follicles. PERB11 is also present in the upper keratin layers but there is relative deficiency in the intermediate layers. These findings suggest a possible role for PERB11 and other MHC genes in the pathogenesis of psoriasis. PMID:10691930

  15. The Relationship Between Gene Polymorphism of Leptin and Leptin Receptor and Growth Hormone Deficiency.

    PubMed

    He, Jinshui; Fang, Yanling; Lin, Xinfu; Zhou, Huowang; Zhu, Shaobo; Zhang, Yugui; Yang, Huicong; Ye, Xiaoling

    2016-02-26

    BACKGROUND Growth hormone deficiency (GHD) is a major cause of congenital short stature. GHD patients have significantly decreased serum leptin levels, which are regulated by gene polymorphism of leptin and leptin receptor. This study thus investigated the relationship between gene polymorphism and susceptibility to GHD. MATERIAL AND METHODS A case-control study was performed using 180 GHD children in addition to 160 healthy controls. After the extraction of whole genomic DNA, the genotypes of leptin and leptin receptor gene loci were analyzed by sequencing for single-nucleotide polymorphism. RESULTS The frequency distribution of all alleles identified in leptin gene (loci rs7799039) and leptin receptor gene (loci rs1137100 and rs1137101) fit Hardy-Weinberg equilibrium. There was a significant difference in allele frequency at loci rs7799039 or rs1137101, as individuals with heterozygous GA allele had lower (rs7799039) or higher (rs1137101) GHD risk. No significant difference in allele frequency was discovered at loci rs1137100 (p>0.05), which was unrelated to GHD susceptibility. CONCLUSIONS Gene polymorphism of leptin (loci rs7799039) and leptin receptor (loci rs1137101) are correlated with GHD susceptibility.

  16. Genetic polymorphism in three glutathione s-transferase genes and breast cancer risk

    SciTech Connect

    Woldegiorgis, S.; Ahmed, R.C.; Zhen, Y.

    The role of the glutathione S-transferase (GST) enzyme family is to detoxify environmental toxins and carcinogens and to protect organisms from their adverse effects, including cancer. The genes GSTM1, GSTP1, and GSTT1 code for three GSTs involved in the detoxification of carcinogens, such as polycyclic aromatic hydrocarbons (PAHs) and benzene. In humans, GSTM1 is deleted in about 50% of the population, GSTT1 is absent in about 20%, whereas the GSTP1 gene has a single base polymorphism resulting in an enzyme with reduced activity. Epidemiological studies indicate that GST polymorphisms increase the level of carcinogen-induced DNA damage and several studies havemore » found a correlation of polymorphisms in one of the GST genes and an increased risk for certain cancers. We examined the role of polymorphisms in genes coding for these three GST enzymes in breast cancer. A breast tissue collection consisting of specimens of breast cancer patients and non-cancer controls was analyzed by polymerase chain reaction (PCR) for the presence or absence of the GSTM1 and GSTT1 genes and for GSTP1 single base polymorphism by PCR/RFLP. We found that GSTM1 and GSTT1 deletions occurred more frequently in cases than in controls, and GSTP1 polymorphism was more frequent in controls. The effective detoxifier (putative low-risk) genotype (defined as presence of both GSTM1 and GSTT1 genes and GSTP1 wild type) was less frequent in cases than controls (16% vs. 23%, respectively). The poor detoxifier (putative high-risk) genotype was more frequent in cases than controls. However, the sample size of this study was too small to provide conclusive results.« less

  17. [Aldose reductase gene polymorphism and rate of appearance of retinopathy in non insulin dependent diabetics].

    PubMed

    Olmos, P; Acosta, A M; Schiaffino, R; Díaz, R; Alvarado, D; O'Brien, A; Muñoz, X; Arriagada, P; Claro, J C; Vega, R; Vollrath, V; Velasco, S; Emmerich, M; Maiz, A

    1999-04-01

    Recent studies suggest that polymorphisms associated to the aldose reductase gene could be related to early retinopathy in noninsulin dependent diabetics (NIDDM). There is also new interest on the genetic modulation of coagulation factors in relation to this complication. To look for a possible relationship between the rate of appearance of retinopathy and the genotype of (AC)n polymorphic marker associated to aldose reductase gene. A random sample of 27 NIDDM, aged 68.1 +/- 10.6 years, with a mean diabetes duration of 20.7 +/- 4.8 years and a mean glycosilated hemoglobin of 10.6 +/- 1.6%, was studied. The genotype of the (AC)n, polymorphic marker associated to the 5' end of the aldose reductase (ALR2) gene was determined by 32P-PCR plus sequenciation. Mutations of the factor XIII-A gene were studied by single stranded conformational polymorphism, sequenciation and restriction fragment length polymorphism. Four patients lacked the (AC)24 and had a higher rate of appearance of retinopathy than patients with the (AC)24 allele (0.0167 and 0.0907 score points per year respectively, p = 0.047). Both groups had similar glycosilated hemoglobin (11.7 +/- 0.2 and 10.5 +/- 1.6% respectively). Factor XIII gene mutations were not related to the rate of appearance of retinopathy. Our data suggest that the absence of the (AC)24 allele of the (AC)n polymorphic marker associated to the 5' end of the aldose reductase gene, is associated to a five fold reduction of retinopathy appearance rate.

  18. No association of apolipoprotein B gene polymorphism and blood lipids in obese Egyptian subjects.

    PubMed

    Bogari, Neda M; Abdel-Latif, Azza M; Hassan, Maha A; Ramadan, Abeer; Fawzy, Ahmed

    2015-03-18

    Several environmental and genetic factors are associated with high levels of lipids in obese patients. Apolipoprotein B (ApoB) is the major protein component of low-density lipoproteins (LDL), very-low density lipoproteins (VLDL) and chylomicrons and plays a central role in lipid metabolism. Several apoB restriction fragment length polymorphisms (XbaI, EcoRI, MspI) have been reported to be associated with variation in lipid levels and obesity. To date, no data are available on the relationship between XbaI polymorphism and lipid levels in Egyptian populations. Following clinical profiling, 178 obese (body mass index [BMI] >25 kg/m(2)) and 178 age-matched non-obese (BMI ≤ 25 kg/m(2)) subjects were included in this case-control study. All samples were analysed for total cholesterol, triglycerides and HDL-cholesterol. Genetic analysis of apoB XbaI (X) was performed using Polymerase Chain Reaction-Restriction Fragment Length polymorphism (PCR-RFLP). The aim of this study was to assess the association of apoB XbaI gene polymorphism (X) and lipid profiles in obese and non-obese Egyptian populations. Obese subjects demonstrated significantly higher values of waist-to-hip ratio, blood pressure, and total lipid. However, in our sample we did not find significant differences in apoB XbaI gene polymorphism (X) genotype or allele frequencies. Moreover, none of the studied lipid parameters showed any association with the gene polymorphism. This study reveals no significant association of apoB XbaI gene polymorphism (X) with obesity or lipid profiles in an Egyptian population.

  19. 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.

  20. 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.

  1. DRD2/ANKK1 gene polymorphisms in forensic autopsies of methamphetamine intoxication fatalities.

    PubMed

    Matsusue, Aya; Ishikawa, Takaki; Ikeda, Tomoya; Tani, Naoto; Arima, Hisatomi; Waters, Brian; Hara, Kenji; Kashiwagi, Masayuki; Takayama, Mio; Ikematsu, Natsuki; Kubo, Shin-Ichi

    2018-04-22

    Dopamine D2 receptor/ankyrin repeat and kinase domain containing 1 (DRD2/ANKK1) gene polymorphisms have been associated with responses to psychotropic drugs and addiction. We analyzed two DRD2/ANKK1 polymorphisms, Taq1A and -141C Ins/Del, in 37 fatal methamphetamine (MA) intoxication cases and 235 control cases in which MA and psychotropic drugs were not detected. The association among polymorphism, cause of death, and cerebrospinal fluid (CSF) dopamine concentration was evaluated. The Taq1A polymorphism distribution in the fatal MA intoxication cases differed from in the controls (P = 0.030) with a significantly high A1/A1 + A1/A2 genotype frequency. No significant associations were observed between -141C Ins/Del polymorphisms and MA intoxication cases or between DRD2/ANKK1 polymorphisms and CSF dopamine concentrations. Our findings suggest that the DRD2/ANKK1 Taq1A polymorphism is associated with susceptibility to fatal MA intoxication. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Polymorphisms of interleukin-1β and MUC7 genes in burning mouth syndrome.

    PubMed

    Kim, Moon-Jong; Kim, Jihoon; Chang, Ji-Youn; Kim, Yoon-Young; Kho, Hong-Seop

    2017-04-01

    The objectives of the present study are to compare polymorphisms of the IL-1β and MUC7 genes between patients with burning mouth syndrome (BMS) and controls and to investigate relationships between these polymorphisms and clinical characteristics in BMS patients. Forty female BMS patients and 40 gender- and age-matched controls were included. Genomic DNA was extracted from saliva samples. Single-nucleotide polymorphisms of IL-1β -511 and +3954 and variation in number of tandem repeat (VNTR) polymorphism of MUC7 were analyzed. Relationships between genotypic polymorphism data and clinical characteristics in BMS patients were also analyzed. There were no significant differences in the genotypes of IL-1β -511 and +3954 and of MUC7 between the groups. There were no significant differences in symptom duration and intensity of BMS patients according to their IL-1β and MUC7 genotypes. The T allele of IL-1β -511 showed associations with psychometry results in BMS patients: paranoid ideation (P = 0.014), Global Severity Index (P = 0.025), and Positive Symptom Total (P = 0.008). The genotypic polymorphisms of IL-1β -511 and +3954, and of MUC7 VNTR, had no direct associations with the development of BMS. However, the T allele of IL-1β -511 may increase the risk of BMS by increasing psychological asthenia. The genotypic polymorphisms of IL-1β -511 may increase the risk for the development of BMS by increasing psychological asthenia.

  3. Uterine leiomyoma is associated with a polymorphism in the interleukin 1-beta gene.

    PubMed

    Pietrowski, Detlef; Thewes, Roberta; Sator, Michael; Denschlag, Dominik; Keck, Christoph; Tempfer, Clemens

    2009-08-01

    To investigate whether polymorphisms in the interleukin-1beta (IL-1beta) gene are associated with uterine leiomyoma. Case-control study in a collective of 131 patients and 280 controls. Genotyping of the IL-1beta-511 and IL-1beta-3954 polymorphism was performed by PCR amplification and subsequent RFLP analysis. A significant difference in the allele frequencies of the IL-1beta-511 Cpolymorphism was found. Allele frequencies of the IL-1beta-511 Cpolymorphism were 70.6% (C allele) in the patient group and 57.1% in the control group [P < 0.0002; odds ratio (OR) 1.81; 95% confidence interval (CI): 1.32-2.47]. The genotype distributions showed also differences using a dominant genotype model (C/C vs. C/T+T/T; P < 0.0002; OR 2.73; 95% CI: 1.77-4.2). No difference was found in the IL-1beta-3954 polymorphism. The IL-1beta-511 promoter polymorphism is related to an increased susceptibility to uterine leiomyoma, suggesting that this polymorphism does contribute to the development of this disease.

  4. 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.

  5. DNA repair genes polymorphisms and genetic susceptibility to Philadelphia-negative myeloproliferative neoplasms in a Portuguese population: The role of base excision repair genes polymorphisms.

    PubMed

    Azevedo, Ana P; Silva, Susana N; De Lima, João P; Reichert, Alice; Lima, Fernando; Júnior, Esmeraldina; Rueff, José

    2017-06-01

    The role of base excision repair (BER) genes in Philadelphia-negative (PN)-myeloproliferative neoplasms (MPNs) susceptibility was evaluated by genotyping eight polymorphisms [apurinic/apyrimidinic endodeoxyribonuclease 1, mutY DNA glycosylase, earlier mutY homolog ( E. coli ) (MUTYH), 8-oxoguanine DNA glycosylase 1, poly (ADP-ribose) polymerase (PARP) 1, PARP4 and X-ray repair cross-complementing 1 (XRCC1)] in a case-control study involving 133 Caucasian Portuguese patients. The results did not reveal a correlation between individual BER polymorphisms and PN-MPNs when considered as a whole. However, stratification for essential thrombocythaemia revealed i) borderline effect/tendency to increased risk when carrying at least one variant allele for XRCC1_399 single-nucleotide polymorphism (SNP); ii) decreased risk for Janus kinase 2-positive patients carrying at least one variant allele for XRCC1_399 SNP; and iii) decreased risk in females carrying at least one variant allele for MUTYH SNP. Combination of alleles demonstrated an increased risk to PN-MPNs for one specific haplogroup. These findings may provide evidence for gene variants in susceptibility to MPNs. Indeed, common variants in DNA repair genes may hamper the capacity to repair DNA, thus increasing cancer susceptibility.

  6. DNA repair genes polymorphisms and genetic susceptibility to Philadelphia-negative myeloproliferative neoplasms in a Portuguese population: The role of base excision repair genes polymorphisms

    PubMed Central

    Azevedo, Ana P.; Silva, Susana N.; De Lima, João P.; Reichert, Alice; Lima, Fernando; Júnior, Esmeraldina; Rueff, José

    2017-01-01

    The role of base excision repair (BER) genes in Philadelphia-negative (PN)-myeloproliferative neoplasms (MPNs) susceptibility was evaluated by genotyping eight polymorphisms [apurinic/apyrimidinic endodeoxyribonuclease 1, mutY DNA glycosylase, earlier mutY homolog (E. coli) (MUTYH), 8-oxoguanine DNA glycosylase 1, poly (ADP-ribose) polymerase (PARP) 1, PARP4 and X-ray repair cross-complementing 1 (XRCC1)] in a case-control study involving 133 Caucasian Portuguese patients. The results did not reveal a correlation between individual BER polymorphisms and PN-MPNs when considered as a whole. However, stratification for essential thrombocythaemia revealed i) borderline effect/tendency to increased risk when carrying at least one variant allele for XRCC1_399 single-nucleotide polymorphism (SNP); ii) decreased risk for Janus kinase 2-positive patients carrying at least one variant allele for XRCC1_399 SNP; and iii) decreased risk in females carrying at least one variant allele for MUTYH SNP. Combination of alleles demonstrated an increased risk to PN-MPNs for one specific haplogroup. These findings may provide evidence for gene variants in susceptibility to MPNs. Indeed, common variants in DNA repair genes may hamper the capacity to repair DNA, thus increasing cancer susceptibility. PMID:28599464

  7. Lack of associations between AURKA gene polymorphisms and neuroblastoma susceptibility in Chinese children.

    PubMed

    Tang, Jue; Qian, Yuanmin; Zhu, Jinhong; Zhang, Jiao; Wang, Feng-Hua; Zeng, Jia-Hang; Liang, Jiang-Hua; Wang, Hui; Xia, Huimin; He, Jing; Liu, Wei

    2018-05-29

    Previous studies have demonstrated that polymorphisms in the AURKA gene are associated with various types of cancer. In neuroblastoma, AURKA protein product regulates N-myc protein levels and plays a critical role in tumorigenesis. To investigate the association between three AURKA polymorphisms (rs1047972 C>T, rs2273535 T>A, and rs8173 G>C) and neuroblastoma susceptibility in Chinese populations, we performed this two-center case-control study including 393 neuroblastoma cases and 812 controls. Two study populations were recruited from two different regions in China. No significant associations were identified amongst any of the three AURKA polymorphisms and the risk of neuroblastoma. Similar observations were found in the stratified analysis. In conclusion, our results indicate that none of the AURKA polymorphisms are associated with neuroblastoma susceptibility in two distinct Chinese populations. Further studies with larger sample sizes and different ethnicities are warranted to validate our results. © 2018 The Author(s).

  8. 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.

  9. Neonatal cerebral sinovenous thrombosis: Two cases, two different gene polymorphisms and risk factors.

    PubMed

    Turan, Özden; Anuk-İnce, Deniz; Olcay, Lale; Sezer, Taner; Gülleroğlu, Kaan; Yılmaz-Çelik, Zerrin; Ecevit, Ayşe

    2017-01-01

    Turan Ö, Anuk-İnce D, Olcay L, Sezer T, Gülleroğlu K, Yılmaz-Çelik Z, Ecevit A. Neonatal cerebral sinovenous thrombosis: Two cases, two different gene polymorphisms and risk factors. Turk J Pediatr 2017; 59: 71-75. Cerebral sinovenous thrombosis (CSVT) is a rare disease in the neonatal period and also the greatest risk of neonatal mortality and morbidity. In this report, we presented two cases with CSVT and different risk factors. One of these cases had methylenetetrahydrofolate reductase (MTHFR) C677T homozygous polymorphism and the other case had both MTHFR A1298C homozygous polymorphism, plasminogen activator inhibitor-1 (PAI-1) 4G/ 5G polymorphism and elevated lipoprotein a. Early diagnosis and prompt initiation of therapy of neonatal CSVT may prevent neonatal mortality and poor long-term neurodevelopmental outcomes.

  10. 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.

  11. [Observation on gene polymorphism of Rh blood group in Chinese Han nationality].

    PubMed

    Lan, Jiong-Cai; Wang, Cong-Rong; Wei, Ya-Ming; Zhou, Hua-You; Cao, Qiong; Zhang, Yin-Ze; Jiang, KuReXi; Wu, Da-Lin; Liu, Zhong

    2003-12-01

    To observe the gene polymorphism of Rh blood group in unrelated random individuals and families for Chinese Han nationality, polymerase chain reaction-sequence specific primer (PCR-SSP) was used to amplify the Rh C/E gene, RhD gene, exons, intron 2 and 10, insert and Rh Box in 160 blood samples of RhD positive unrelated individuals and 71 samples of RhD negative unrelated individuals and 7 samples of families whose probands were RhD-negative. The results showed that RhD genes of RhD-negative individuals with C antigens were polymorphism, three forms were found for D exon including intact, partial deletion and complete deletion exons. Insert fragments and Rh Box were found in most cases of families whose probands were RhD-negative and its inheritance accorded with the Mendel's Law, and it did not affect the expression of RhD gene. "Normal" RhD exon 4 amplifying product was not found in all of the samples. It was concluded that gene structure of the RhD-negative in Chinese was polymorphism, intact, partial deletion and complete deletion exons were found in the individuals with C antigen and probably existed specific D (nf) Ce haplotype. The function of insert was uncertain. The Rh gene sequences of Chinese Han nationality are different from those of Caucasian and the Rh gene library based on Han nationality should be established.

  12. Evaluation of ACE gene I/D polymorphism in Iranian elite athletes.

    PubMed

    Shahmoradi, Somayeh; Ahmadalipour, Ali; Salehi, Mansoor

    2014-01-01

    Angiotensin converting enzyme (ACE) is an important gene, which is associated with the successful physical activity. The ACE gene has a major polymorphism (I/D) in intron 16 that determines its plasma and tissue levels. In this study, we aimed to determine whether there is an association between this polymorphism and sports performance in our studied population including elite athletes of different sports disciplines. We investigated allele frequency and genotype distribution of the ACE gene in 156 Iranian elite athletes compared to 163 healthy individuals. We also investigated this allele frequency between elite athletes in three functional groups of endurance, power, and mixed sports performances. DNA was extracted from peripheral blood, and polymerase chain reaction (PCR) method was performed on intron 16 of the ACE gene. The ACE genotype was determined for each subject. Statistical analysis was performed by SPSS 15, and results were analyzed by Chi-Square test. There was a significant difference in genotype distribution and allele frequency of the ACE gene in athletes and control group (P = 0.05, P = 0.03, respectively). There was also a significant difference in allele frequency of the ACE gene in 3 groups of athletes with different sports disciplines (P = 0.045). Proportion of the ACE gene D allele was greater in elite endurance athletes (37 high-distance cyclists) than two other groups. Findings of the present study demonstrated that there is an association between the ACE gene I/D polymorphism and sports performance in Iranian elite athletes.

  13. Interleukin gene polymorphisms in Chinese Han population with breast cancer, a case-control study.

    PubMed

    Zuo, Xiaoxiao; Li, Miao; Yang, Ya; Liang, Tiansong; Yang, Hongyao; Zhao, Xinhan; Yang, Daoke

    2018-04-06

    Cytokines are known as important regulators of the cancer involved in inflammatory and immunological responses. This fact and plethora of gene polymorphism data prompted us to investigate IL1 gene polymorphisms in breast cancer (BC) patients. Totally, 530 patients with BC and 628 healthy control women were studied. The genetic polymorphisms for IL1 were analyzed by Massarray Sequencing method. Three single nucleotide polymorphisms (SNPs) identified in IL1B, IL1R1 gene are thought to influence breast cancer risk. The results of the association between IL-1B, IL1R1 polymorphisms and breast cancer risk have significant. We found that the variant TT genotype of rs10490571 was associated with a significantly increased breast cancer risk (TT vs. CC: OR = 2.82, 95% CI = 1.12-7.08, P = 0.047 for the codominant model). For rs16944 (AG vs. GG: OR = 0.60, 95% CI = 0.41-0.90, P = 0.034 for the codominant model) and rs1143623 (CG vs. CC: OR = 0.65, 95% CI = 0.45-0.94, P = 0.023 for the codominant model) have significant associations were found in genetic models. In conclusion, the present analysis suggests a correlation of polymorphic markers within the IL-1 gene locus with the risk in developing breast cancer. Taken together with our finding that IL1B, IL1R1 gene three SNP are also associated with the risk for the disease, we suggest that inflammation via innate and adaptive immunity contributes to multifactorial hereditary predisposition to pathogenesis of the breast cancer.

  14. Interleukin gene polymorphisms in Chinese Han population with breast cancer, a case-control study

    PubMed Central

    Yang, Ya; Liang, Tiansong; Yang, Hongyao; Zhao, Xinhan; Yang, Daoke

    2018-01-01

    Cytokines are known as important regulators of the cancer involved in inflammatory and immunological responses. This fact and plethora of gene polymorphism data prompted us to investigate IL1 gene polymorphisms in breast cancer (BC) patients. Totally, 530 patients with BC and 628 healthy control women were studied. The genetic polymorphisms for IL1 were analyzed by Massarray Sequencing method. Three single nucleotide polymorphisms (SNPs) identified in IL1B, IL1R1 gene are thought to influence breast cancer risk. The results of the association between IL-1B, IL1R1 polymorphisms and breast cancer risk have significant. We found that the variant TT genotype of rs10490571 was associated with a significantly increased breast cancer risk (TT vs. CC: OR = 2.82, 95% CI = 1.12–7.08, P = 0.047 for the codominant model). For rs16944 (AG vs. GG: OR = 0.60, 95% CI = 0.41–0.90, P = 0.034 for the codominant model) and rs1143623 (CG vs. CC: OR = 0.65, 95% CI = 0.45–0.94, P = 0.023 for the codominant model) have significant associations were found in genetic models. In conclusion, the present analysis suggests a correlation of polymorphic markers within the IL-1 gene locus with the risk in developing breast cancer. Taken together with our finding that IL1B, IL1R1 gene three SNP are also associated with the risk for the disease, we suggest that inflammation via innate and adaptive immunity contributes to multifactorial hereditary predisposition to pathogenesis of the breast cancer. PMID:29719585

  15. Microarray study of single nucleotide polymorphisms and expression of ATP-binding cassette genes in breast tumors

    NASA Astrophysics Data System (ADS)

    Tsyganov, M. M.; Ibragimova, M. K.; Karabut, I. V.; Freydin, M. B.; Choinzonov, E. L.; Litvyakov, N. V.

    2015-11-01

    Our previous research establishes that changes of expression of the ATP-binding cassette genes family is connected with the neoadjuvant chemotherapy effect. However, the mechanism of regulation of resistance gene expression remains unclear. As many researchers believe, single nucleotide polymorphisms can be involved in this process. Thereupon, microarray analysis is used to study polymorphisms in ATP-binding cassette genes. It is thus found that MDR gene expression is connected with 5 polymorphisms, i.e. rs241432, rs241429, rs241430, rs3784867, rs59409230, which participate in the regulation of expression of own genes.

  16. Tetra primer ARMS-PCR relates folate/homocysteine pathway genes and ACE gene polymorphism with coronary artery disease.

    PubMed

    Masud, Rizwan; Qureshi, Irfan Zia

    2011-09-01

    Cardiovascular disorders and coronary artery disease (CAD) are significant contributors to morbidity and mortality in heart patients. As genes of the folate/homocysteine pathway have been linked with the vascular disease, we investigated association of these gene polymorphisms with CAD/myocardial infarction (MI) using the novel approach of tetraprimer ARMS-PCR. A total of 230 participants (129 MI cases, 101 normal subjects) were recruited. We genotyped rs1801133 and rs1801131 SNPs in 5'10' methylenetetrahydrofolate reductase (MTHFR), rs1805087 SNP in 5' methyltetrahydrofolate homocysteine methyltransferase (MTR), rs662 SNP in paroxanse1 (PON1), and rs5742905 polymorphism in cystathionine beta synthase (CBS). Angiotensin converting enzyme (ACE) insertion/deletion polymorphism was detected through conventional PCR. Covariates included blood pressure, fasting blood sugar, serum cholesterol, and creatinine concentrations. Our results showed allele frequencies at rs1801133, rs1801131, rs1805087 and the ACE insertion/deletion (I/D) polymorphism varied between cases and controls. Logistic regression, after adjusting for covariates, demonstrated significant associations of rs1801133 and rs1805087 with CAD in the additive, dominant, and genotype model. In contrast, ACE I/D polymorphism was significantly related with CAD where recessive model was applied. Gene-gene interaction against the disease status revealed two polymorphism groups: rs1801133, rs662, and rs1805087; and rs1801131, rs662, and ACE I/D. Only the latter interaction maintained significance after adjusted for covariates. Our study concludes that folate pathway variants exert contributory influence on susceptibility to CAD. We further suggest that tetraprimer ARMS-PCR successfully resolves the genotypes in selected samples and might prove to be a superior technique compared to the conventional approach.

  17. Polymorphisms of the IL-1beta and IL-1beta-inducible genes in ulcerative colitis.

    PubMed

    Nohara, Hiroaki; Saito, Yuki; Higaki, Singo; Okayama, Naoko; Hamanaka, Yuichiro; Okita, Kiwamu; Hinoda, Yuji

    2002-11-01

    Ulcerative colitis (UC) is a chronic disorder of undetermined etiology, but a genetic predisposition to UC is well recognized. Among cytokines induced in UC, interleukin 1 (IL-1) appears to have a central role because of its immunological upregulatory and proinflammatory activities. The aim of this study was to assess whether UC is associated with polymorphisms of the IL-1beta gene and three additional genes inducible with IL-1beta in Japanese subjects. A total of 96 patients with UC and 106 ethnically matched controls were genotyped at polymorphic sites in IL-1beta, matrix metalloproteinase 1 (MMP-1), matrix metalloproteinase 3 (MMP-3), and inducible nitric oxide synthase (iNOS) genes, using polymerase chain reaction (PCR)-based methods. There was no significant difference in genotype distributions of IL-1beta, MMP-1, MMP-3, and iNOS genes between controls and UC patients in a Japanese population. Also, no significant association of those polymorphisms with various clinical parameters of the patients was found. However, concerning association of age at onset with clinical factors in UC, the frequency of pancolitis was significantly higher in UC patients with age at onset being less than 30 years than in those more than 30 years of age (P = 0.049). No association of the IL-1beta and three IL-1beta-inducible gene polymorphisms with UC was observed in a Japanese population.

  18. N-acetyltransferase gene polymorphisms & plasma isoniazid concentrations in patients with tuberculosis.

    PubMed

    Hemanth Kumar, A K; Ramesh, K; Kannan, T; Sudha, V; Haribabu, Hemalatha; Lavanya, J; Swaminathan, Soumya; Ramachandran, Geetha

    2017-01-01

    Variations in the N-acetyltransferase (NAT2) gene among different populations could affect the metabolism and disposition of isoniazid (INH). This study was performed to genotype NAT2 gene polymorphisms in tuberculosis (TB) patients from Chennai, India, and compare plasma INH concentrations among the different genotypes. Adult patients with TB treated in the Revised National TB Control Programme (RNTCP) in Chennai, Tamil Nadu, were genotyped for NAT2 gene polymorphism, and two-hour post-dosing INH concentrations were compared between the different genotypes. Plasma INH was determined by high-performance liquid chromatography. Genotyping of the NAT2 gene polymorphism was performed by real-time polymerase chain reaction method. Among the 326 patients genotyped, there were 189 (58%), 114 (35%) and 23 (7%) slow, intermediate and fast acetylators, respectively. The median two-hour INH concentrations in slow, intermediate and fast acetylators were 10.2, 8.1 and 4.1 μg/ml, respectively. The differences in INH concentrations among the three genotypes were significant (P<0.001). Genotyping of TB patients from south India for NAT2 gene polymorphism revealed that 58 per cent of the study population comprised slow acetylators. Two-hour INH concentrations differed significantly among the three genotypes.

  19. N-acetyltransferase gene polymorphisms & plasma isoniazid concentrations in patients with tuberculosis

    PubMed Central

    Hemanth Kumar, A. K.; Ramesh, K.; Kannan, T.; Sudha, V.; Haribabu, Hemalatha; Lavanya, J.; Swaminathan, Soumya; Ramachandran, Geetha

    2017-01-01

    Background & objectives: Variations in the N-acetyltransferase (NAT2) gene among different populations could affect the metabolism and disposition of isoniazid (INH). This study was performed to genotype NAT2 gene polymorphisms in tuberculosis (TB) patients from Chennai, India, and compare plasma INH concentrations among the different genotypes. Methods: Adult patients with TB treated in the Revised National TB Control Programme (RNTCP) in Chennai, Tamil Nadu, were genotyped for NAT2 gene polymorphism, and two-hour post-dosing INH concentrations were compared between the different genotypes. Plasma INH was determined by high-performance liquid chromatography. Genotyping of the NAT2 gene polymorphism was performed by real-time polymerase chain reaction method. Results: Among the 326 patients genotyped, there were 189 (58%), 114 (35%) and 23 (7%) slow, intermediate and fast acetylators, respectively. The median two-hour INH concentrations in slow, intermediate and fast acetylators were 10.2, 8.1 and 4.1 μg/ml, respectively. The differences in INH concentrations among the three genotypes were significant (P<0.001). Interpretation & conclusions: Genotyping of TB patients from south India for NAT2 gene polymorphism revealed that 58 per cent of the study population comprised slow acetylators. Two-hour INH concentrations differed significantly among the three genotypes. PMID:28574024

  20. [Correlation analysis of G870A CCND1 gene polymorphism with digestive system tumors].

    PubMed

    Yang, Shu-Min; Shi, Ya-Lin

    2016-11-20

    To study the correlation of G870A CCND1 gene polymorphism and digestive system tumors. From August 2010 to August 2014, 164 digestive system cancer patients (including 82 patients with gastric cancer and 82 with colorectal cancer) and 82 healthy subjects (control group) were examined with PCR-restriction fragment length polymorphism (PCR-RFLP). The distribution of CCND1 gene G870A frequency in the 3 groups and its association with tumor staging and grading were analyzed. The frequencies of the GG, GA and AA genotypes in G870A CCND1 gene loci in patients with gastric cancer and colorectal cancer differed significantly from those in the control group (P<0.05). G870A CCND1 gene polymorphism was closely associated with an increased risk of digestive system tumors (P<0.05). The GA and AA genotypes were associated with a significantly higher risk of digestive system cancer risk than the GG genotype (P<0.05), and their frequencies were significantly higher in patients with tumors of higher pathological grade and in those in advanced tumor stages (P<0.05). G870A CCND1 gene polymorphism is associated with the risk of digestive system tumors. The allele A is associated with an increased risk of digestive system tumors and correlated with the tumor differentiation and staging of the tumor.

  1. [Study on association of CTLA4 gene polymorphism with Grave's disease in Guangxi Zhuang nationality population].

    PubMed

    Liang, Xing-huan; Qin, Ying-fen; Ma, Yan; Xie, Xin-rong; Xie, Kai-qing; Luo, Zuo-jie

    2006-06-01

    To investigate the relationship between the polymorphic (AT)n repeats in 3ountranslated region of exon 4 of CTLA4 gene [CTLA4(AT)n] and Graveso disease (GD) in Zhuang nationality population of Guangxi province. The studied groups comprised 48 patients with GD and 44 normal controls. Amplification of target DNA was carried out by polymerase chain reaction (PCR). The amplified products were run by 8% polyacrylamide gel electrophoresis, and then followed by 0.1% silver staining. Some of amplified products were sequenced directly. Nineteen alleles of CTLA4 gene microsatellite polymorphism were found in Guangxi Zhuang nationality individuals. The 106 bp long allele was apparently increased in patients with GD of Zhuang nationality but not in healthy controls (P< 0.05). CTLA4 gene microsatellite polymorphism is strongly associated with Graveso disease in Zhuang nationality population of Guangxi province. CTLA4(AT)n 106 bp may be the susceptible gene in GD patients of Zhuang nationality in Guangxi; 19 alleles of CTLA4 gene microsatellite polymorphism were found in Guangxi Zhuang nationality individuals.

  2. Association of interleukin 8 -251 A/T gene polymorphism with periodontitis in Indonesia

    NASA Astrophysics Data System (ADS)

    Jessica, C.; Alwadris, T. T.; Prasetyo, S. R.; Puspitawati, R.; Auerkari, E. I.

    2018-05-01

    Periodontitis is a chronic multifactorial disease resulting from an interaction between periodontal pathogen bacteria, host, and environmental factors. Genetics has been identified to contribute to the pathogenesis and susceptibility of periodontitis, and interleukin 8 (IL-8) gene is expressing one of the chemokines involved in the inflammation process. This study aimed to evaluate the association of IL-8 -251 A/T gene polymorphism with periodontitis in Indonesian subjects. The study was conducted by genotyping 72 samples of patients with various severity of periodontitis and 41 samples of healthy controls group using PCR-RFLP method. Genotypes of the IL-8 gene polymorphism in periodontitis patients were not significantly different with those in healthy controls. Those with TT genotype were 3.40 times less likely to develop periodontitis compared to AA genotype (95% CI). There was a significant difference in allele frequencies (p < 0.05, OR = 1.828, 95% CI), suggesting that allele T is a risk factor to periodontitis. Statistical analyses with Chi-square testing showed no significant association of IL-8 -251 A/T gene polymorphism and the severity of periodontitis in Indonesia. However, IL-8 -251 A/T gene polymorphism might contribute to the susceptibility of periodontitis.

  3. IL-10 and IL-12B gene polymorphisms in a multiethnic Malaysian population.

    PubMed

    Sam, S S; Teoh, B T; AbuBakar, S

    2015-04-13

    Inheritance of polymorphisms in the interleukin (IL)-10 promoter and IL-12B genes, which influence cytokine production and activities, may define the balance in T helper response in infection and autoimmune diseases. In the present study, we investigated the distribution of the IL-10 promoter and IL-12B gene polymorphisms in a multiethnic Malaysian population. Overall, our findings suggest that the IL-12B and IL-10 -592 genotypes were distributed homogenously across all major ethnic groups, including Malays, Chinese, and Indians, except for polymorphisms at IL-10 -1082. At this gene locus, the ethnic Chinese showed a significantly lower allele frequency of -1082G (2.1%) compared to the Malay (12.2%) and Indian (15.3%) populations. Results for the IL-12B and IL-10 gene polymorphisms were consistent with those reported for the Asian population, but markedly different from those of the African and Caucasian populations. Our findings suggest that there are specific genetic variations between different ethnic groups, which should be examined in all gene population-based association studies.

  4. Association between polymorphisms of the insulin-degrading enzyme gene and late-onset Alzheimer disease.

    PubMed

    Wang, Shitao; He, Feiyan; Wang, Ying

    2015-06-01

    The insulin-degrading enzyme (IDE) gene is a strong positional and biological candidate for late-onset Alzheimer disease (LOAD) susceptibility, with recent studies independently demonstrating an association between IDE gene variants and LOAD. However, previous data have been controversial. To investigate the relationship between IDE gene polymorphisms and LOAD risk, a case-control association study of 406 Han Chinese participants in Xinjiang, China, was undertaken. The LOAD and control groups consisted of 202 and 204 participants, respectively. The single-nucleotide polymorphisms rs1887922 and rs1999764 of the IDE gene were linked to LOAD incidence. The presence of the CT+CC genotype of rs1999764 had a protective effect compared to the TT genotype (adjusted P=.0001; odds ratio [OR]=0.226; 95% confidence interval [CI]=0.116-0.441), while the CT+CC genotype of rs1887922 was associated with increased LOAD risk (adjusted P=.0001; OR=3.640; 95% CI=1.889-7.016). Moreover, the effects of rs1887922 and rs1999764 were associated with LOAD risk independent of the apolipoprotein E ∊4 polymorphism and were more significant in men and women, respectively. These results demonstrate that the polymorphisms rs1887922 and rs1999764 of the IDE gene are associated with LOAD susceptibility in the Xinjiang Han population. © The Author(s) 2014.

  5. Combinations of SERPINB5 gene polymorphisms and environmental factors are associated with oral cancer risks.

    PubMed

    Tsai, Hsiu-Ting; Hsieh, Ming-Ju; Lin, Chiao-Wen; Su, Shih-Chi; Miao, Nae-Fang; Yang, Shun-Fa; Huang, Hui-Chuan; Lai, Fu-Chih; Liu, Yu-Fan

    2017-01-01

    We identified rs17071138 T/C, rs3744941 C/T, and rs8089104 T/C gene polymorphisms of SERPINB5 (mammary serine protease inhibitor) that are specific to patients with oral cancer susceptibility and their clinicopathological status. In total, 1342 participants, including 601 healthy controls and 741 patients with oral cancer, were recruited for this study. Allelic discrimination of rs17071138 T/C, rs3744941 C/T, and rs8089104 T/C of the SERPINB5 gene was assessed by a real-time PCR with a TaqMan assay. We found that individuals carrying the polymorphic rs17071138 and rs8089104 are more susceptible to oral cancer (OR, 1.57; 95% CI, 1.07~2.31 and OR, 1.58; 95% CI, 1.04~2.39, respectively). Among oral cancer-related risk factor exposures, the individuals carrying the polymorphic rs17071138 had 4.26- (95% CI: 1.65~11.01; p = 0.002), 2.34- (95% CI: 1.19~4.61; p = 0.01), and 2.34-fold (95% CI: 1.38~3.96; p = 0.001) higher risks of developing oral cancer. Heterozygous TC of the SERPINB5 rs17071138 polymorphism may be a factor that increases susceptibility to oral cancer. Interactions of gene-to-gene and gene-to-oral cancer-related environmental risk factors have a synergetic effect that can further enhance oral cancer development.

  6. Genetic polymorphisms in the ESR1 gene and cerebral infarction risk: a meta-analysis.

    PubMed

    Gao, Hong-Hua; Gao, Lian-Bo; Wen, Jia-Mei

    2014-09-01

    A number of studies have documented that estrogen receptor α (ESR1) may play an important role in the development and progression of cerebral infarction, but many existing studies have yielded inconclusive results. This meta-analysis was performed to evaluate the relationships between ESR1 genetic polymorphisms and cerebral infarction risk. The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched for relevant articles published before October 1, 2013, without any language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Seven case-control studies were included with a total of 1471 patients with cerebral infarction and 4688 healthy control subjects. Two common single-nucleotide polymorphisms (SNPs) in the ESR1 gene (rs2234693 T>C and rs9340799 A>G) were assessed. Our meta-analysis results revealed that ESR1 genetic polymorphisms might increase the risk of cerebral infarction. Subgroup analysis by SNP type indicated that both rs2234693 and rs9340799 polymorphisms in the ESR1 gene were strongly associated with an increased risk of cerebral infarction. Further subgroup analysis by ethnicity showed significant associations between ESR1 genetic polymorphisms and increased risk of cerebral infarction among both Asians and Caucasians. In the stratified subgroup analysis by gender, the results suggested that ESR1 genetic polymorphisms were associated with an increased risk of cerebral infarction in the female population. However, there were no statistically significant associations between ESR1 genetic polymorphisms and cerebral infarction risk in the male population. Meta-regression analyses also confirmed that gender might be a main source of heterogeneity. Our findings indicate that ESR1 genetic polymorphisms may contribute to the development of cerebral infarction, especially in the female population.

  7. Clock gene polymorphism and scheduling of migration: a geolocator study of the barn swallow Hirundo rustica

    PubMed Central

    Bazzi, Gaia; Ambrosini, Roberto; Caprioli, Manuela; Costanzo, Alessandra; Liechti, Felix; Gatti, Emanuele; Gianfranceschi, Luca; Podofillini, Stefano; Romano, Andrea; Romano, Maria; Scandolara, Chiara; Saino, Nicola; Rubolini, Diego

    2015-01-01

    Circannual rhythms often rely on endogenous seasonal photoperiodic timers involving ‘clock’ genes, and Clock gene polymorphism has been associated to variation in phenology in some bird species. In the long-distance migratory barn swallow Hirundo rustica, individuals bearing the rare Clock allele with the largest number of C-terminal polyglutamine repeats found in this species (Q8) show a delayed reproduction and moult later. We explored the association between Clock polymorphism and migration scheduling, as gauged by light-level geolocators, in two barn swallow populations (Switzerland; Po Plain, Italy). Genetic polymorphism was low: 91% of the 64 individuals tracked year-round were Q7/Q7 homozygotes. We compared the phenology of the rare genotypes with the phenotypic distribution of Q7/Q7 homozygotes within each population. In Switzerland, compared to Q7/Q7, two Q6/Q7 males departed earlier from the wintering grounds and arrived earlier to their colony in spring, while a single Q7/Q8 female was delayed for both phenophases. On the other hand, in the Po Plain, three Q6/Q7 individuals had a similar phenology compared to Q7/Q7. The Swiss data are suggestive for a role of genetic polymorphism at a candidate phenological gene in shaping migration traits, and support the idea that Clock polymorphism underlies phenological variation in birds. PMID:26197782

  8. CREB1 gene polymorphisms combined with environmental risk factors increase susceptibility to major depressive disorder (MDD)

    PubMed Central

    Wang, Peng; Yang, Yanjie; Yang, Xiuxian; Qiu, Xiaohui; Qiao, Zhengxue; Wang, Lin; Zhu, Xiongzhao; Sui, Hong; Ma, Jingsong

    2015-01-01

    Major depressive disorder (MDD) is one of the most severe psychiatric disorders. The objective of this study was to explore the effects of CREB1 gene polymorphisms on risk of developing MDD and the joint effects of gene-environment interactions. Genotyping was performed by Taqman allelic discrimination assay among 586 patients and 586 healthy controls. A significant impact on rs6740584 genotype distribution was found for childhood trauma (P = 0.015). We did not find an association of CREB1 polymorphisms with MDD susceptibility. However, we found a significantly increased risk associated with the interactions of CREB1 polymorphisms and drinking (OR = 11.67, 95% CI = 2.52-54.18; OR = 11.52, 95% CI = 2.55-51.95 for rs11904814; OR = 4.18, 95% CI = 1.87-9.38; OR = 5.02, 95% CI = 2.27-11.14 for rs6740584; OR = 7.58, 95% CI = 2.05-27.98; OR = 7.59, 95% CI = 2.12-27.14 for rs2553206; OR = 8.37, 95% CI = 3.02-23.23; OR = 7.84, 95% CI = 2.93-20.98 for rs2551941). We also noted that CREB polymorphisms combined with family harmony and childhood trauma conferred increased susceptibility for MDD. In conclusion, polymorphisms in the CREB gene may not be independently associated with MDD risk, but they are likely to confer increased susceptibility by interacting with environmental risk factors in the Chinese population. PMID:25755794

  9. MYO9B gene polymorphisms are associated with the risk of inflammatory bowel diseases

    PubMed Central

    Yu, Qiang; Zhu, Chun-Fu; Kong, Zhi-Jun; Zhao, Hui; Tang, Li-Ming; Qin, Xi-Hu

    2016-01-01

    Myosin IXB (MYO9B) gene polymorphisms have been extensively investigated in terms of their associations with inflammatory bowel disease (IBD), with contradictory results. The aim of this meta-analysis was to evaluate associations between MY09B gene polymorphisms and the risk of IBD, Crohn's disease (CD) and ulcerative colitis (UC). Eligible studies from PubMed, Embase, and CNKI databases were identified. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Ten studies published in eight papers reporting 8,975 cases and 9,482 controls were included in this meta-analysis. Five MY09B gene polymorphisms were evaluated: rs1545620, rs962917, rs1457092, rs2305764, and rs2305767. Our data suggested that the rs1545620 polymorphism was associated with a decreased risk of IBD. A similar result was found for rs2305767 and UC. The rs962917 single nucleotide polymorphism (SNP) increased the risk of IBD, CD and UC. Moreover, rs1457092 increased the risk of IBD and UC. Rs2305764 was also associated with an increased risk of IBD. Furthermore, stratification analyses indicated that rs1545620 decreased the risk of IBD, while rs962917 increased the risk of IBD, CD and UC in Caucasian populations. To sum up, our data indicate that these five SNPs in MY09B are significantly associated with the risk of IBD. PMID:27556856

  10. Analysis of cytotoxic T lymphocyte associated antigen 4 gene polymorphisms in patients with ulcerative colitis.

    PubMed

    Lankarani, Kamran B; Karbasi, Ashraf; Kalantari, Tahereh; Yarmohammadi, Hooman; Saberi-Firoozi, Mehdi; Alizadeh-Naeeni, Mahvash; Taghavi, Ali R; Fattahi, Mahammad R; Ghaderi, Abbas

    2006-02-01

    Ulcerative colitis (UC) is a multifactorial disease associated with dysregulated immunity. Recently, cytotoxic T lymphocyte associated antigen 4 (CTLA-4) gene polymorphisms have been reported in association with several autoimmune diseases in several populations. In the present study, the possible implication of the CTLA-4 gene as a risk factor for UC in the Iranian population was investigated. One hundred UC patients and 100 healthy subjects were studied. CTLA-4 exon 1 position 49 (A/G: codon 17: Thr/Ala) polymorphisms were investigated by polymerase chain reaction single strand confirmation polymorphism method. Four of the patients and one of the healthy controls were excluded from the study because of incomplete DNA extraction. The allele frequencies of A and G in 96 patients (A: 66.1%; G: 33.9%) were not significantly different from the 99 control subjects (A: 63.1%; G: 36.9%, P > 0.05). No significant differences in the distribution of genotype frequencies were observed between A + 49G gene polymorphisms and UC in the Iranian population (P > 0.05). CTLA-4 polymorphism is not associated with UC in the Iranian population.

  11. [Association of estrogen receptor gene polymorphism with cerebral infarction, a case-control study].

    PubMed

    Zhang, Yan; Xie, Ruping; Wang, Yinhua; Chen, Dafang; Wang, Guoying; Xu, Xiping

    2002-11-10

    To explore the association between estrogen receptor (ER) gene PvuII and XbaI polymorphisms and cerebral infarction among Chinese Han people. Samples of peripheral blood white cell were extracted among 234 patients with cerebral infarction, aged 63.9 +/- 10.3, and 259 controls without cerebrovascular disease, aged 59.2 +/- 9.2, all of Chinese Han nationality. PCR-RFLP and genotyping of ER PvuII and XbaI polymorphisms were performed. Multiple Logistic regression analysis was made to explore the risk factors for cerebral infarction. After adjustment for major confounders including age, gender, smoking, alcohol drinking, education, history of hypertension, diabetes mellitus, coronary artery disease and hyperlipoidemia, multiple Logistic regression analysis showed that: (1) The Pp genotype of ER PvuII polymorphism increased the risk of cerebral infarction significantly (OR = 1.97, 95% CI: 1.21 - 3.21); (2) The ER XbaI polymorphism was not in association with cerebral infarction significantly; (3) The PPXx/Ppxx genotypes increased the risk of cerebral infarction significantly (OR = 1.67, 2.52 and 2.18 respectively, P < 0.05) before or after all subjects were stratified by the history of hypertension or hyperlipoidemia; and (4) The positive interaction between the ER PvuII polymorphism and the presence of hypertension or diabetes or hyperlipoidemia could increase the risk of cerebral infarction significantly. ER gene may be one of the genetic candidate genes for cerebral infarction among Chinese Han population.

  12. Evaluation of eNOS gene polymorphisms in relation to BMD in postmenopausal women.

    PubMed

    Firat, Sibel Cubukcu; Cetin, Zafer; Samanci, Nehir; Aydin, Funda; Balci, Nilufer; Gungor, Firat; Firat, Mehmet Ziya; Luleci, Guven; Karauzum, Sibel Berker

    2009-08-20

    The aim of the present study was to evaluate the relations between T(-786)C and Glu298Asp polymorphisms of the endothelial nitric oxide synthase (eNOS) gene and BMD in postmenopausal Turkish women. The T(-786)C and Glu298Asp polymorphisms were genotyped by PCR-RFLP method in 311 postmenopausal osteoporotic women (OP) and in 305 age-matched postmenopausal females (CG) with normal BMD. None of the SNPs of the eNOS gene was significantly associated with BMD at the lumbar spine, femoral neck, Ward's triangle and femoral trochanter in the combined group. Mean BMD values were therefore found to be similar across the genotypes in postmenopausal Turkish women. However, there was a significant association between the T(-786)C polymorphism and BMD values at the lumbar spine in the normal control group (P=0.005), and at the femoral trochanter in the osteoporotic patients (P=0.046). The mean value of the lumbar spine BMD in the normal controls was significantly higher in women with the TC genotype of the T(-786)C polymorphism than in women with the TT genotype (P=0.0012). Women with the CC genotype of the T(-786)C polymorphism in the osteoporotic patients had significantly higher BMD value at the femoral trochanter than those with the TC (P=0.018) and TT genotypes (P=0.024). Frequencies of the TC heterozygotes for T(-786)C polymorphism were significantly higher among osteoporotic subjects than normal controls. Also, the CC and TT genotype frequencies of control group were significantly higher than those of the osteoporotic group at the femoral neck. We conclude that, although the biological role of the nitric oxide synthases is well established, our study does not suggest that eNOS gene polymorphisms, T(-786)C and Glu298Asp, are major contributors to adult bone mineral density in the postmenopausal Turkish women.

  13. Polymorphism of the beta3-adrenergic receptor gene affects basal metabolic rate in obese Finns.

    PubMed

    Sipiläinen, R; Uusitupa, M; Heikkinen, S; Rissanen, A; Laakso, M

    1997-01-01

    Low basal metabolic rate (BMR) is a risk factor for weight gain and obesity. The polymorphism at codon 64 of the beta3-adrenergic receptor gene has been suggested to be associated with BMR. We investigated the frequency of the Trp64Arg of the beta3-adrenergic receptor gene and the effects of this polymorphism on BMR in obese Finns. Altogether, 170 obese subjects (29 men, 141 women, BMI 34.7 +/- 3.8 kg/m2, mean +/- SD) participated in the study. The frequency of the Trp64Arg polymorphism was 19%. None of the obese subjects were homozygous for the Arg-encoding allele. The frequency of the Trp64Arg polymorphism in obese Finns did not differ from nonobese and normoglycemic control subjects. BMR adjusted for lean body mass and age was lower in subjects with the Trp64Arg polymorphism (n = 20) than in normal homozygotes Trp64Trp (n = 99) (1,569 +/- 73 vs. 1,635 +/- 142 kcal/day, P = 0.004). For the female group (n = 98), the respective values were 1,501 +/- 66 kcal/day vs. 1,568 +/- 127 kcal/day (P = 0.004). There were no significant differences in weight, BMI, waist-to-hip ratio, lean body mass, percentage of fat, and respiratory quotient between the groups with or without the Trp64Arg polymorphism. Neither serum glucose nor insulin levels differed between the two groups. We conclude that the Trp64Arg polymorphism of the beta3-adrenergic receptor gene affects basal metabolic rate in obese Finns but does not have significant effect on glucose metabolism.

  14. Genetic polymorphisms in the formaldehyde dehydrogenase gene and their biological significance.

    PubMed

    Just, Walter; Zeller, Jasmin; Riegert, Clarissa; Speit, Günter

    2011-11-30

    The GSH-dependent formaldehyde dehydrogenase (FDH) is the most important enzyme for the metabolic inactivation of formaldehyde. We studied three polymorphisms of this gene with the intention to elucidate their relevance for inter-individual differences in the protection against the (geno-)toxicity of FA. The first polymorphism (rs11568816) was investigated using real-time PCR and restriction fragment analysis in 150 subjects. However, we did not find the polymorphic sequence in any of the subjects. We studied a second polymorphism (rs17028487), representing a base exchange (c.*114A>G) in exon 9 of the FDH gene. We analyzed 70 subjects with the SNaPshot Primer Extension method and subsequent analysis in a ABI PRISM 3100, but no variant allele was identified. A third polymorphism, rs13832 in exon 9 (c.*493G>T), was studied in a group of 105 subjects by the SNaPshot Primer Extension method. 43 of the subjects were heterozygous for the polymorphism (G/T), 46 homozygous for the T allele, and 16 were homozygous for the G-allele. Real-time RT-PCR measurements of FDH mRNA did not indicate a significant difference in transcript levels between the heterozygous and the homozygous groups. The in vitro comet assay after FA exposure of blood samples obtained from 5 homozygous GG and 3 homozygous TT subjects did not lead to a significant difference between these two groups. Altogether, our study did not identify biologically relevant polymorphisms in transcribed regions of the FDH gene, which may lead to inter-individual differences in the metabolic inactivation of FA. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  15. 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

  16. Association of monoamine oxidase A gene polymorphism with Alzheimer's disease and Lewy body variant.

    PubMed

    Takehashi, Masanori; Tanaka, Seigo; Masliah, Eliezer; Ueda, Kunihiro

    2002-07-19

    The association between (GT)n dinucleotide repeats in monoamine oxidase gene loci, monoamine oxidase A (MAOA) and B (MAOB), and Parkinson's disease (PD), Alzheimer's disease (AD), and Lewy body variant (LBV) of AD were determined. MAOA-GT polymorphisms were significantly associated with pure AD and LBV. MAOA-GT allele 113 was excessively represented in pure AD and LBV compared with controls. Furthermore, the frequency of females homozygous for MAOA-GT allele 113 was higher in pure AD and LBV than controls by 2.79- and 2.77-fold, respectively. In contrast, there was no association between MAOA-GT or MAOB-GT polymorphisms and PD. These results suggest that polymorphisms within the MAOA gene may have implication in AD pathology shared by pure AD and LBV.

  17. Distribution of the most common polymorphisms in TYMS gene in Slavic population of central Europe.

    PubMed

    Pastorakova, A; Chandogova, D; Chandoga, J; Luha, J; Bohmer, D; Malova, J; Braxatorisova, T; Juhosova, M; Reznakova, S; Petrovic, R

    2017-01-01

    Thymidylate synthetase (TS) plays a critical role in the de novo synthesis of dTMP inside the cell. Therefore, TS is a suitable target for cytotoxic drugs such as fluoropyrimidines. Drug efficacy and toxicity depend on the intracellular level of TS, which is significantly influenced by the polymorphisms in the 5'UTR (TSER - rs45445694, TSER*3G>C - rs2853542) and 3'UTR (1494del TTAAAG - rs151264360) of TYMS gene. Polymorphic variants of TYMS gene affect TS activity via gene expression and transcript stability. Patients who undergo fluoropyrimidine therapy may benefit from genetic testing prior to the administration of chemotherapy. At the 5' terminus of TYMS, there is a polymorphic region represented by a variable number of 28bp long tandem repeats (2-9 tandems) with the G or C nucleotide variant (SNP G>C). The 3'end of TYMS gene may decrease the stability of mRNA in the case of 6 base deletion (1494del6, D). In our study, we have focused on testing of TYMS gene polymorphisms, determination of TYMS variant frequencies in Western Slavic population and comparison of Slovak population with other populations.We performed identification of 5'UTR (rs45445694 - TSER*2 or TSER*3; rs2853542 - TSER*3G>C; TSER*3+ins6) and 3'UTR (rs151264360/1494del6/D) polymorphic regions of TYMS gene among 96 volunteers by PCR-RFLP and fragment analysis. Slovak frequencies of selected polymorphisms were established as follows: the frequency of TSER*2, TSER*3, TSER*3G>C, 1494del6/D and I to be 41%, 59%, 34%, 37.5% and 62.5% respectively. The high resolution of the capillary electrophoresis technique allowed among TSER*3 group identification of a subgroup of four individuals with rare 6bp insertion in 3R allele, id est 2.1% TSER*3+ins6 allele frequency. In our study, we have revealed individuals with rare G>C substitution in the first 28bp tandem repeat of TSER*2 promoter enhancer region (rs183205964) as well, the overall frequency of this polymorphic allele in Slovak population was 2.1%. Our

  18. Dopamine D{sub 3} receptor gene: Organization transcript variants, and polymorphism associated with schizophrenia

    SciTech Connect

    Griffon, N.; Pilon, C.; Martres, M.P.

    1996-02-16

    DNA fragments from a genomic library were used to establish the partial structure of the human dopamine D{sub 3} receptor gene (DRD3). Its coding sequence contains 6 exons and stretches over 40,000 base pairs. The complete DRD3 transcript and three shorter variants, in which the second and/or third exon are deleted, were detected in similar proportions in brains from four controls and three psychiatric patients. The Msp I polymorphism was localized in the fifth intron of the gene, 40,000 base pairs downstream the Bal I polymorphism and a PCR-based method was developed for genotyping this polymorphism. The distributions of themore » Msp I and Bal I genotypes were not independent in 297 individuals ({chi}{sup 2} = 10.5, df = 4, P = 0.03), but only a weak association was found between allele 1 of the Bal I polymorphism and allele 2 of the Msp I polymorphism ({chi}{sup 2} = 3.99, df = 1, P = 0.04). The previously reported association between homozygosity at both alleles of the Bal I polymorphism and schizophrenia was presently maintained in an extended sample, comprising 119 DSM-III-R chronic schizophrenics and 85 controls ({chi}{sup 2}= 5.3, df = 1, P = 0.02) and found more important in males than in females. The presence of the Bal I allele 2 is associated with an early age at onset, particularly in males (df = 35, t value = 2.6, P = 0.014). In the same sample, allelic frequencies, genotype counts, and proportion of homozygotes for the Msp I polymorphism did not differ between schizophrenics and controls ({chi}{sup 2}= 0.06, df = 1, P = 0.80, {chi}{sup 2} = 0.22, df = 1, P = 0.90 and {chi}{sup 2} = 0.16, df = 1, P = 0.69, respectively). The large distance of the Msp I polymorphism from the Bal I polymorphism and its localization in the 3{prime} part of the gene may explain the discrepant results obtained with the two polymorphisms. 36 refs., 2 figs., 4 tabs.« less

  19. Polymorphisms of the TRPV2 and TRPV3 genes associated with fibromyalgia in a Korean population.

    PubMed

    Park, Dong-Jin; Kim, Seong-Ho; Nah, Seong-Su; Lee, Ji Hyun; Kim, Seong-Kyu; Lee, Yeon-Ah; Hong, Seung-Jae; Kim, Hyun-Sook; Lee, Hye-Soon; Kim, Hyoun Ah; Joung, Chung-Il; Kim, Sang-Hyon; Lee, Shin-Seok

    2016-08-01

    Researchers continue to gather evidence that transient receptor potential vanilloid (TRPV) channels contribute towards pain signalling pathways. However, it is unknown whether polymorphisms of the TRPV gene are associated with FM. For the first time, we investigated the association between the polymorphisms of the TRPV2 and TRPV3 genes, FM susceptibility and the severity of the symptoms. A total of 409 patients with FM and 423 controls were enrolled from 10 medical centres that participated in the Korean nationwide FM survey. The alleles and genotypes at three positions [rs3813768(C > G), rs8121(C > T) and rs1129235(C > A)] in the TRPV2 gene and two positions [rs7216486 (G > A) and rs395357(C > T)] in the TRPV3 gene were genotyped. The frequencies of the alleles and genotypes of individual TRPV2 and TRPV3 genes were not significantly associated with FM susceptibility. However, the GTA haplotype of TRPV2 showed a defence against FM susceptibility (P = 0.035). In addition, polymorphisms of TRPV3 were associated with symptom severity in FM patients. The single nucleotide polymorphism rs395357 of TRPV3 was associated with the scores of the Brief Fatigue Inventory (P = 0.017) in FM patients. Furthermore, haplotypes of TRPV3 were associated with the Brief Fatigue Inventory and the 36-item Short-Form Health Survey mental health summary scores (P = 0.036). This study was the first to evaluate the associations of TRPV gene polymorphisms with FM. Our results suggest that certain TRPV2 haplotypes may have a protective role against FM and that some genotypes and haplotypes of TRPV3 contribute towards the symptoms of FM. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Mismatch repair gene MSH3 polymorphism is associated with the risk of sporadic prostate cancer

    PubMed Central

    Hirata, Hiroshi; Hinoda, Yuji; Kawamoto, Ken; Kikuno, Nobuyuki; Suehiro, Yutaka; Okayama, Naoko; Tanaka, Yuichiro; Dahiya, Rajvir

    2014-01-01

    Purpose The mismatch repair (MMR) system is a DNA repair mechanism that corrects mispaired bases during DNA replication errors. Cancer cells deficient in the MMR proteins have a 102 –103-fold increase in the mutation rate. Single nucleotide polymorphisms (SNPs) of MMR genes have been shown to cause a reduction in DNA repair activity. We hypothesized that mismatch repair gene polymorphism could be a risk factor for prostate cancer (PC) and that p53 Pro/Pro genotype carriers could influence MSH3 and MSH6 polymorphisms. Material and Methods DNA samples from 110 cases of prostate cancer and healthy controls (n=110) were analyzed by SSCP and PCR-RFLP to determine the genotypic frequency of five different polymorphic loci on two MMR genes (MSH3 and MSH6) and p53 codon72. The chi-square test was applied to compare the genotype frequency between patients and controls. Results A significant increase in the G/A+A/A genotype of MSH3 Pro222Pro was observed in patients compared to controls (OR, 1.87; 95% CI, 1.0–3.5). The frequency of A/G + G/G genotypes of MSH3 exon23 Thr1036Ala also tended to increase in patients (OR, 1.57; 95% CI, 0.92–2.72). Among p53 codon72 Arg/Pro + Pro/Pro carriers, the frequency of the AG + GG genotype of MSH3 exon23 was significantly increased in patients compared to controls (OR = 2.1, 95% CI; 1.05–4.34). Conclusion This is the first report on the association of MSH3 gene polymorphisms in prostate cancer. These results suggest that the MSH3 polymorphism may be a risk factor for prostate cancer. PMID:18355840

  1. Haemochromatosis HFE gene polymorphisms as potential modifiers of hereditary nonpolyposis colorectal cancer risk and onset age.

    PubMed

    Shi, Zumin; Johnstone, Daniel; Talseth-Palmer, Bente A; Evans, Tiffany-Jane; Spigelman, Allan D; Groombridge, Claire; Milward, Elizabeth A; Olynyk, John K; Suchy, Janina; Kurzawski, Grzegorz; Lubinski, Jan; Scott, Rodney J

    2009-07-01

    Hereditary nonpolyposis colorectal cancer (HNPCC) is characterized by germline mutations in DNA mismatch repair genes; however, variation in disease expression suggests that there are potential modifying factors. Polymorphisms of the HFE gene, which cause the iron overload disorder hereditary haemochromatosis, have been proposed as potential risk factors for the development of colorectal cancer (CRC). To understand the relationship between HNPCC disease phenotype and polymorphisms of the HFE gene, a total of 362 individuals from Australia and Poland with confirmed causative MMR gene mutations were genotyped for the HFE C282Y and H63D polymorphisms. A significantly increased risk of developing CRC was observed for H63D homozygotes when compared with combined wild-type homozygotes and heterozygotes (hazard ratio = 2.93, p = 0.007). Evidence for earlier CRC onset was also observed in H63D homozygotes with a median age of onset 6 years earlier than wild type or heterozygous participants (44 vs. 50 years of age). This effect was significant by all tests used (log-rank test p = 0.026, Wilcoxon p = 0.044, Tarone-Ware p = 0.035). No association was identified for heterozygosity of either polymorphism and limitations on power-prevented investigation of C282Y homozygosity or compound C282Y/H63D heterozygosity. In the Australian sample only, women had a significantly reduced risk of developing CRC when compared with men (hazard ratio = 0.58, p = 0.012) independent of HFE genotype for either single nucleotide polymorphisms. In conclusion, homozygosity for the HFE H63D polymorphism seems to be a genetic modifier of disease expression in HNPCC. Understanding the mechanisms by which HFE interrelates with colorectal malignancies could lead to reduction of disease risk in HNPCC.

  2. Tumor necrosis factor-alpha and interleukin-4 gene polymorphisms in Chinese patients with gout.

    PubMed

    Chen, M-L; Tsai, F-J; Tsai, C-H; Huang, C-M

    2007-01-01

    The purpose of this study was to examine whether polymorphisms of interleukin-4 (IL-4) (promoter-590 and intron 3) and tumor necrosis factor-alpha (TNF-alpha) promoter-308 genes are markers of susceptibility to or clinical manifestations of gout in Taiwanese patients. The study included 196 Taiwanese patients with gout and 103 unrelated healthy control subjects living in central Taiwan. Polymorphisms of the IL-4 (promoter-590 and intron 3) and TNF-alpha (promoter-308) genes were typed from genomic DNA. Allelic frequencies and carriage rates were then compared between gout patients and control subjects. The correlation between allelic frequencies, carriage rates and clinical manifestations of gout were evaluated. No significant differences were observed in the allelic frequencies and carriage rates of the IL-4 (promoter-590 and intron 3) and TNF-alpha gene polymorphisms between patients with gout and healthy control subjects. Furthermore, the IL-4 (promoter-590 and intron 3) and TNF-alpha genotypes were not found to be associated with the clinical and laboratory profiles in gout patients. However, there was a significant difference in the TNF-alphapolymorphism genotype between patients with and without hypertriglyceridemia (P=0.001, xi2=11.47, OR=10.3, 95%CI=3.57-29.7). The results of our study suggest that polymorphisms of the IL-4 (promoter-590 and intron 3) and TNF-alpha promoter-308 genes are not related to gout in Chinese patients in Taiwan.

  3. The SPO11-C631T gene polymorphism and male infertility risk: a meta-analysis.

    PubMed

    Ren, Zheng-Ju; Ren, Peng-Wei; Yang, Bo; Liao, Jian; Liu, Sheng-Zhuo; Fang, Kun; Ren, Shang-Qing; Liu, Liang-Ren; Dong, Qiang

    2017-11-01

    To evaluate the association between the SPO11 gene C631T polymorphism and the risk of male infertility. We conducted a search on PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), China biology medical literature database (CBM), VIP, and Chinese literature database (Wan Fang) on 31 March 2016. Odds ratio (OR) and 95% confidence interval (95%CI) were used to assess the strength of associations. A total of five studies including 542 cases and 510 controls were involved in this meta-analysis. The pooled results indicated that the SPO11 gene C631T polymorphism was significantly associated with increased risk of male infertility (TT + CT vs. CC: OR = 4.14, 95%CI = 2.48-6.89; CT vs. CC: OR = 4.34, 95%CI = 2.56-7.34; T vs. C: OR = 4.35, 95%CI = 2.58-7.34). Subgroup analysis of different countries proved the relationship between SPO11 gene C631T polymorphism and male infertility risk in Chinese, but not in Iranian peoples. In conclusion, this study suggested that SPO11 gene C631T polymorphism may contribute as a genetic factor susceptible to cause male infertility. Furthermore, more large sample and representative population-based cases and well-matched controls are needed to validate our results.

  4. BIALLELIC POLYMORPHISM IN THE INTRON REGION OF B-TUBULIN GENE OF CRYPTOSPORIDIUM PARASITES

    EPA Science Inventory

    Nucleotide sequencing of polymerase chain reaction-amplified intron region of the Cryptosporidium parvum B-tubulin gene in 26 human and 15 animal isolates revealed distinct genetic polymorphism between the human and bovine genotypes. The separation of 2 genotypes of C. parvum is...

  5. The effects of single nucleotide polymorphisms (SNPs) of calpastatin (CAST) gene on meat tenderness of yak.

    USDA-ARS?s Scientific Manuscript database

    The association of single nucleotide polymorphisms (SNPs) of calpastatin (CAST) gene with shear force of 2.54 cm steaks from M. longissimus dorsi from Gannan yaks (Bos grunniens, n=181) was studied. Yaks were harvested at 2, 3, and 4 yr of age (n=51, 59, and 71, respectively), and samples of each ya...

  6. Analysis of -1082 IL-10 gene polymorphism in Iranian patients with generalized aggressive periodontitis.

    PubMed

    Mellati, Ehsan; Arab, Hamid R; Tavakkol-Afshari, Jalil; Ebadian, Ahmad R; Radvar, Mehrdad

    2007-11-01

    Periodontitis is a multifactorial disease and its severe forms, such as aggressive periodontitis, are suggested to have a genetic basis. Among the genetic factors, polymorphisms in cytokine genes have recently been described in susceptibility to periodontitis. IL-10 is a multi-functional cytokine thought to play a role in the pathogenesis of periodontitis. A substitution G/A polymorphism in the promoter region of the IL-10 gene at position -1082 has been associated with different amounts of IL-10 production. The aim of the present study was to investigate the possible links between -1082(G/A) polymorphism of the IL-10 gene and the generalized form of aggressive periodontitis. This study included 52 Iranian Khorasanian (north-east province of Iran) subjects suffering from generalized aggressive periodontitis referred to the Periodontology Department of Mashhad Dental School. They were compared to 61 age and sex-matched healthy controls of the same race. DNA was isolated from peripheral blood cells and genotyping was performed by means of the amplification refractory mutation system polymerase chain reaction (ARMS-PCR) method. Data were analyzed using the chi-squared test. There was no marked difference in genotype frequencies between the controls and generalized aggressive periodontitis patients (p=0.585). Moreover, no association between patients and normal subjects was found in their allele frequency (p=0.329). We conclude that the polymorphic nucleotide A at position -1082 of the IL-10 gene is not associated with generalized aggressive periodontitis in the Iranian population.

  7. Polymorphisms in the hemagglutinin gene influenced the viral shedding of pandemic 2009 influenza virus in swine

    USDA-ARS?s Scientific Manuscript database

    The contribution of influenza virus quasi-species for transmission efficiency and replication is poorly understood. In the present study we show that naturally occurring polymorphisms present in the hemagglutinin (HA) gene of two 2009 pandemic H1N1 isolates, A/California/04/2009 (Ca/09) and A/Mexico...

  8. Landscape heterogeneity predicts gene flow in a widespread polymorphic bumble bee, Bombus bifarius (Hymentoptera: Apidae).

    USDA-ARS?s Scientific Manuscript database

    Bombus bifarius is a widespread bumble bee that occurs in montane regions of western North America. This species has several major color polymorphisms, and shows evidence of genetic structuring among regional populations. We test whether this structure is evidence for discrete gene flow barriers tha...

  9. The Association between Infants' Self-Regulatory Behavior and MAOA Gene Polymorphism

    ERIC Educational Resources Information Center

    Zhang, Minghao; Chen, Xinyin; Way, Niobe; Yoshikawa, Hirokazu; Deng, Huihua; Ke, Xiaoyan; Yu, Weiwei; Chen, Ping; He, Chuan; Chi, Xia; Lu, Zuhong

    2011-01-01

    Self-regulatory behavior in early childhood is an important characteristic that has considerable implications for the development of adaptive and maladaptive functioning. The present study investigated the relations between a functional polymorphism in the upstream region of monoamine oxidase A gene (MAOA) and self-regulatory behavior in a sample…

  10. Relationship of Serum Klotho Level With ACE Gene Polymorphism in Stable Kidney Allograft Recipients.

    PubMed

    Zaare Nahandi, Maryam; Ardalan, Mohamad Reza; Banagozar Mohamadi, Ali; Ghorbani Haghjo, Amir; Jabbarpor Bonyadi, Morteza; Mohamadian, Tahere

    2017-03-01

    The kidney is the main source of serum Klotho production. Immunosuppressive agents could affect the kidney in this regard. The effect of the ACE gene polymorphism on Klotho production is a less studied area. This study aimed to assess serum Klotho and ACE gene in a group of stable kidney transplant recipients. In a cross-sectional study, 30 kidney transplant recipients with stable allograft function and 27 healthy young individuals were assessed for their serum Klotho levels. The ACE gene polymorphisms were studied in both groups. Klotho level was higher in kidney transplant recipients than the controls, but the difference was not significant (2.76 ± 2.41 ng/mL versus 2.01 ± 1.41 ng/mL, respectively). In both groups, serum Klotho level was higher in those with the I>I polymorphism, the men, those with higher glomerular filtration rate, and younger individuals, but the differences did not reach a significant level. Higher body mass index was significantly associated with lower serum Klotho level in both groups. Klotho level after kidney transplantation meets the range in healthy individuals, and it is not affected by the ACE gene polymorphism.

  11. Assessment of the relationship between ACE I/D gene polymorphism and renal allograft survival.

    PubMed

    Yang, Chun-Hua; Lu, Yi; Chen, Xue-Xia; Xian, Wen-Feng; Tu, Wei-Feng; Li, Hong-Yan

    2015-12-01

    The relationship between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and renal allograft survival after renal transplantation from the published reports are still debatable. This study was performed to evaluate the relationship between the ACE I/D gene polymorphism and renal allograft survival after renal transplantation using meta-analysis. Eligible studies were identified from PubMed and Cochrane Library on 1 November 2014, and eligible studies were recruited and synthesized using a meta-analysis methodology. Twelve investigations were included in this meta-analysis for the assessment of the relationship between the ACE I/D gene polymorphism and renal allograft survival. In this meta-analysis, the ACE I/D gene polymorphism was not associated with renal allograft survival after renal transplantation for overall populations, Caucasians, Brazilians and Africans. Interestingly, the ACE D allele and DD genotype were associated with renal allograft survival after renal transplantation in the Asian population. ACE D allele and DD genotype were associated with renal allograft survival after renal transplantation in the Asian population. However, more studies should be performed to confirm this association. © The Author(s) 2015.

  12. High-density polymorphisms analysis of 23 candidate genes for association with bone mineral density.

    PubMed

    Giroux, Sylvie; Elfassihi, Latifa; Clément, Valérie; Bussières, Johanne; Bureau, Alexandre; Cole, David E C; Rousseau, François

    2010-11-01

    Osteoporosis is a bone disease characterized by low bone mineral density (BMD), a highly heritable and polygenic trait. Women are more prone than men to develop osteoporosis due to a lower peak bone mass and accelerated bone loss at menopause. Peak bone mass has been convincingly shown to be due to genetic factors with heritability up to 80%. Menopausal bone loss has been shown to have around 38% to 49% heritability depending on the site studied. To have more statistical power to detect small genetic effects we focused on premenopausal women. We studied 23 candidate genes, some involved in calcium and vitamin-D regulation and others because estrogens strongly induced their gene expression in mice where it was correlated with humerus trabecular bone density. High-density polymorphisms were selected to cover the entire gene variability and 231 polymorphisms were genotyped in a first sample of 709 premenopausal women. Positive associations were retested in a second, independent, sample of 673 premenopausal women. Ten polymorphisms remained associated with BMD in the combined samples and one was further associated in a large sample of postmenopausal women (1401 women). This associated polymorphism was located in the gene CSF3R (granulocyte colony stimulating factor receptor) that had never been associated with BMD before. The results reported in this study suggest a role for CSF3R in the determination of bone density in women. Copyright © 2010 Elsevier Inc. All rights reserved.

  13. An Angiopoietin-2 gene polymorphism in unexplained intrauterine fetal death: a multi-center study.

    PubMed

    Huber, Ambros; Grimm, Christoph; Pietrowski, Detlef; Zeillinger, Robert; Bettendorf, Hertha; Husslein, Peter; Hefler, Lukas

    2005-02-01

    Angiopoietin-2 (Ang-2) is a potent regulator of angiogenesis and vascular tone. As vascular processes have been proposed to be involved in the pathogenesis of pregnancy associated complications such as late unexplained intrauterine fetal death (IUFD), we determined whether a common G/A polymorphism of the Ang-2 gene (ANGPT2) is associated with this condition. In a multicenter case-control study, we evaluated the common G/A polymorphism within exon 4 of the ANGPT2 gene using PCR in 90 women with IUFD and 90 healthy women with at least one uncomplicated full term pregnancy and no history of IUFD. Genotype (p=0.2; OR=1.4 [0.8-2.6]) and allele frequencies (p=0.1; OR=1.4 [0.9-2.1]) of the ANGPT2 polymorphism did not differ between women with IUFD and healthy women. A multivariate regression analysis with smoking habits and preexisting diabetes as covariates did not change the results. We are the first to report on a common polymorphism of the ANGPT2 gene in patients with late IUFD. The investigated ANGPT2 poylmorphism does not seem to be a candidate gene for IUFD in Caucasian women.

  14. Genetic basis of interindividual susceptibility to cancer cachexia: selection of potential candidate gene polymorphisms for association studies.

    PubMed

    Johns, N; Tan, B H; MacMillan, M; Solheim, T S; Ross, J A; Baracos, V E; Damaraju, S; Fearon, K C H

    2014-12-01

    Cancer cachexia is a complex and multifactorial disease. Evolving definitions highlight the fact that a diverse range of biological processes contribute to cancer cachexia. Part of the variation in who will and who will not develop cancer cachexia may be genetically determined. As new definitions, classifications and biological targets continue to evolve, there is a need for reappraisal of the literature for future candidate association studies. This review summarizes genes identified or implicated as well as putative candidate genes contributing to cachexia, identified through diverse technology platforms and model systems to further guide association studies. A systematic search covering 1986-2012 was performed for potential candidate genes / genetic polymorphisms relating to cancer cachexia. All candidate genes were reviewed for functional polymorphisms or clinically significant polymorphisms associated with cachexia using the OMIM and GeneRIF databases. Pathway analysis software was used to reveal possible network associations between genes. Functionality of SNPs/genes was explored based on published literature, algorithms for detecting putative deleterious SNPs and interrogating the database for expression of quantitative trait loci (eQTLs). A total of 154 genes associated with cancer cachexia were identified and explored for functional polymorphisms. Of these 154 genes, 119 had a combined total of 281 polymorphisms with functional and/or clinical significance in terms of cachexia associated with them. Of these, 80 polymorphisms (in 51 genes) were replicated in more than one study with 24 polymorphisms found to influence two or more hallmarks of cachexia (i.e., inflammation, loss of fat mass and/or lean mass and reduced survival). Selection of candidate genes and polymorphisms is a key element of multigene study design. The present study provides a contemporary basis to select genes and/or polymorphisms for further association studies in cancer cachexia, and

  15. Correlation between facial morphology and gene polymorphisms in the Uygur youth population.

    PubMed

    He, Huiyu; Mi, Xue; Zhang, Jiayu; Zhang, Qin; Yao, Yuan; Zhang, Xu; Xiao, Feng; Zhao, Chunping; Zheng, Shutao

    2017-04-25

    Human facial morphology varies considerably among individuals and can be influenced by gene polymorphisms. We explored the effects of single nucleotide polymorphisms (SNPs) on facial features in the Uygur youth population of the Kashi area in Xinjiang, China. Saliva samples were collected from 578 volunteers, and 10 SNPs previously associated with variations in facial physiognomy were genotyped. In parallel, 3D images of the subjects' faces were obtained using grating facial scanning technology. After delimitation of 15 salient landmarks, the correlation between SNPs and the distances between facial landmark pairs was assessed. Analysis of variance revealed that ENPP1 rs7754561 polymorphism was significantly associated with RAla-RLipCn and RLipCn-Sbn linear distances (p = 0.044 and p = 0.012, respectively) as well as RLipCn-Stm curve distance (p = 0.042). The GHR rs6180 polymorphism correlated with RLipCn-Stm linear distance (p = 0.04), while the GHR rs6184 polymorphism correlated with RLipCn-ULipP curve distance (p = 0.047). The FGFR1 rs4647905 polymorphism was associated with LLipCn-Nsn linear distance (p = 0.042). These results reveal that ENPP1 and FGFR1 influence lower anterior face height, the distance from the upper lip to the nasal floor, and lip shape. FGFR1 also influences the lower anterior face height, while GHR is associated with the length and width of the lip.

  16. Porcine NAMPT gene: search for polymorphism, mapping and association studies

    USDA-ARS?s Scientific Manuscript database

    NAMPT encodes for an enzyme catalysing the rate-limiting step in NAD biosynthesis. The extracellular form of the enzyme is known as adipokine visfatin. We detected SNP AM999341:g.669T>C in intron 9 and SNP FN392209:g.358A>G in the promoter of the gene. RH mapping linked the gene to microsatellite SW...

  17. 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.

  18. Is the polymorphism at position -1082 of IL-10 gene associated with visceral leishmaniasis?

    PubMed

    Hajilooi, Mehrdad; Ahmadi, Alireza; Lotfi, Pegah; Matini, Mohammad; Jafari, Davood; Bazmani, Ahad; Momeni, Mohammad

    2014-08-01

    Immune responses play critical roles in the leishmaniasis eradication. IL-10 is a key regulator of immune responses, and the polymorphisms within its promoter region are associated with alteration in its expression. Therefore, this study was designed to examine the correlation between polymorphism at the -1082 position of the IL-10 gene and visceral leishmaniasis (VL). The IL-10 -1082 polymorphism and anti-Leishmania antibody titration were examined in 110 patients with clinical presentation of VL and seropositive for the Leishmania (group 1), 74 seropositive patients but without clinical presentation (group 2) and 113 healthy controls (group 3) using the PCR-RFLP and immunofluorescence techniques, respectively. The polymorphism at IL-10 -1082 (A/G) position was significantly associated with VL and A/G genotype was significantly higher in VL patients when compared to the groups 2 and 3 (P< 0.001). However, the results demonstrated that the A and G alleles were not associated with VL (P= 0.263). Previous investigations have shown that the polymorphism at the -1082 position of the IL-10 gene can influence its expression and also it has been proved that IL-10 level was increased during VL. Our results suggest that the A/G genotype may be considered as a risk factor for VL.

  19. Is the Polymorphism at Position -1082 of IL-10 Gene Associated with Visceral Leishmaniasis?

    PubMed Central

    HAJILOOI, Mehrdad; AHMADI, Alireza; LOTFI, Pegah; MATINI, Mohammad; JAFARI, Davood; BAZMANI, Ahad; MOMENI, Mohammad

    2014-01-01

    Abstract Background Immune responses play critical roles in the leishmaniasis eradication. IL-10 is a key regulator of immune responses, and the polymorphisms within its promoter region are associated with alteration in its expression. Therefore, this study was designed to examine the correlation between polymorphism at the -1082 position of the IL-10 gene and visceral leishmaniasis (VL). Methods The IL-10 -1082 polymorphism and anti-Leishmania antibody titration were examined in 110 patients with clinical presentation of VL and seropositive for the Leishmania (group 1), 74 seropositive patients but without clinical presentation (group 2) and 113 healthy controls (group 3) using the PCR-RFLP and immunofluorescence techniques, respectively. Results The polymorphism at IL-10 -1082 (A/G) position was significantly associated with VL and A/G genotype was significantly higher in VL patients when compared to the groups 2 and 3 (P< 0.001). However, the results demonstrated that the A and G alleles were not associated with VL (P= 0.263). Conclusions Previous investigations have shown that the polymorphism at the -1082 position of the IL-10 gene can influence its expression and also it has been proved that IL-10 level was increased during VL. Our results suggest that the A/G genotype may be considered as a risk factor for VL. PMID:25927040

  20. [Influence of leptin receptor gene K109R polymorphism on the risk of nonalcoholic fatty liver disease and its interaction with PNPLA3 I148M polymorphism].

    PubMed

    An, B Q; Jiang, M; Cheng, Y T; Yuan, C; Lu, L L; Xin, Y N; Xuan, S Y

    2016-05-20

    To investigate the influence of leptin receptor (LEPR) gene K109R polymorphism on the risk of nonalcoholic fatty liver disease (NAFLD) and its interaction with PNPLA3 I148M polymorphism in the Han Chinese population in Qingdao, China. Blood samples were collected from 296 NAFLD patients and 321 healthy controls, and the genotypes of these patients were determined by PCR and genotyping. Related statistical analyses were performed to compare genotypes, alleles, and clinical data between the two groups. Generalized multifactor dimensionality reduction (GMDR) was used to investigate the interaction between LEPR K109R and PNPLA3 I148M genes. The distribution of LEPR K109R genotypes and alleles showed no significant differences between the NAFLD group and the control group (P > 0.05). PNPLA3 I148M gene polymorphisms were closely associated with the risk of NAFLD, and the risk of NAFLD in G mutant gene carriers was 2.07 times that in patients who did not carry this gene (OR = 2.07, 95% CI 1.423-3.013, P < 0.001). The joint action of LEPR K109R and PNPLA3 I148M significantly increased the risk of NAFL (OR = 3.393, 95% CI 1.856-6.201, P < 0.001). In the Han Chinese population in Qingdao, LEPR K109R gene polymorphism is not associated with the risk of NAFLD, but its interaction with PNPLA3 I148M polymorphism can significantly increase the risk of NAFLD.

  1. C282Y polymorphism in the HFE gene is associated with risk of breast cancer.

    PubMed

    Liu, Xiaoyan; Lv, Chunlei; Luan, Xiaorong; Lv, Ming

    2013-10-01

    The C282Y and H63D polymorphisms in the HFE gene have been implicated in susceptibility of breast cancer, but a number of studies have reported inconclusive results. The aim of this study is to investigate the association between the C282Y and H63D polymorphisms in the HFE gene and breast cancer risk by meta-analysis. We searched PubMed and Embase databases, covering all related studies until March 2, 2013. Statistical analysis was performed using STATA 10.0. A total of 7 studies including 1,720 cases and 18,296 controls for HFE C282Y polymorphism and 5 studies including 942 cases and 1,571 controls for HFE H63D polymorphism were included in the meta-analysis. The results showed that HFE C282Y polymorphism was significantly associated with increased risk of breast cancer under homozygotes vs. wild-type model (OR = 2.06, 95%CI = 1.19-3.58) and recessive model (OR = 1.98, 95%CI = 1.14-3.44) but not under heterozygotes vs. wild-type model (OR = 0.97, 95%CI = 0.70-1.35), dominant model (OR = 1.00, 95%CI = 0.72-1.40) and multiplicative model (OR = 1.04, 95%CI = 0.76-1.42). However, we did not find any association between HFE H63D polymorphism and breast cancer risk under all genetic models. This current meta-analysis suggested that C282Y polymorphism rather than H63D might be associated with increased risk of breast cancer.

  2. Wheat CBF gene family: identification of polymorphisms in the CBF coding sequence.

    PubMed

    Mohseni, Sara; Che, Hua; Djillali, Zakia; Dumont, Estelle; Nankeu, Joseph; Danyluk, Jean

    2012-12-01

    Expression of cold-regulated genes needed for protection against freezing stress is mediated, in part, by the CBF transcription factor family. Previous studies with temperate cereals suggested that the CBF gene family in wheat was large, and that CBF genes were at the base of an important low temperature tolerance trait. Therefore, the goal of our study was to identify the CBF repertoire in the freezing-tolerant hexaploid wheat cultivar Norstar, and then to examine if the coding region of CBF genes in two spring cultivars contain polymorphisms that could affect the protein sequence and structure. Our analyses reveal that hexaploid wheat contains a complex CBF family consisting of at least 65 CBF genes of which 60 are known to be expressed in the cultivar Norstar. They represent 27 paralogous genes with 1-3 homeologous copies for the A, B, and D genomes. The cultivar Norstar contains two pseudogenes and at least 24 additional proteins having sequences and (or) structures that deviate from the consensus in the conserved AP2 DNA-binding and (or) C-terminal activation-domains. This suggests that in cultivars such as Norstar, low temperature tolerance may be increased through breeding of additional optimal alleles. The examination of the CBF repertoire present in the two spring cultivars, Chinese Spring and Manitou, reveals that they have additional polymorphisms affecting conserved positions in these domains. Understanding the effects of these polymorphisms will provide additional information for the selection of optimum CBF alleles in Triticeae breeding programs.

  3. Polymorphisms in DNA repair genes and MDR1 and the risk for non-Hodgkin lymphoma.

    PubMed

    Kim, Hee Nam; Kim, Nan Young; Yu, Li; Kim, Yeo-Kyeoung; Lee, Il-Kwon; Yang, Deok-Hwan; Lee, Je-Jung; Shin, Min-Ho; Park, Kyeong-Soo; Choi, Jin-Su; Kim, Hyeoung-Joon

    2014-04-21

    The damage caused by oxidative stress and exposure to cigarette smoke and alcohol necessitate DNA damage repair and transport by multidrug resistance-1 (MDR1). To explore the association between polymorphisms in these genes and non-Hodgkin lymphoma risk, we analyzed 15 polymorphisms of 12 genes in a population-based study in Korea (694 cases and 1700 controls). Four genotypes of DNA repair pathway genes (XRCC1 399 GA, OGG1 326 GG, BRCA1 871 TT, and WRN 787 TT) were associated with a decreased risk for NHL [odds ratio (OR)XRCC1 GA=0.80, p=0.02; OROGG1 GG=0.70, p=0.008; ORBRCA1 TT=0.71, p=0.048; ORWRN TT=0.68, p=0.01]. Conversely, the MGMT 115 CT genotype was associated with an increased risk for NHL (OR=1.25, p=0.04). In the MDR1 gene, the 1236 CC genotype was associated with a decreased risk for NHL (OR=0.74, p=0.04), and the 3435 CT and TT genotypes were associated with an increased risk (OR3435CT=1.50, p<0.0001; OR3435TT=1.43, p=0.02). These results suggest that polymorphisms in the DNA repair genes XRCC1, OGG1, BRCA1, WRN1, and MGMT and in the MDR1 gene may affect the risk for NHL in Korean patients.

  4. Leptin and leptin receptor gene polymorphisms are correlated with production performance in the Arctic fox.

    PubMed

    Zhang, M; Bai, X J

    2015-05-25

    The polymerase chain reaction-single-strand conformation polymorphism technique was employed to measure mononucleotide diversity in the coding region of the leptin and leptin receptor genes in the Arctic fox. The relationships between specific genetic mutations and reproductive performance in Arctic foxes were determined to im-prove breeding strategies. We found that a leptin gene polymorphism was significantly associated with body weight (P < 0.01), abdominal circumference (P < 0.01), and fur length (P < 0.01). Furthermore, a polymorphism in the leptin receptor gene was associated with carcass weight and guard hair length (P < 0.01). Leptin and leptin receptor gene combinatorial genotypes were significantly associated with abdominal circumference, fur length (P < 0.01), and body weight (P < 0.05). The leptin gene is thus a key gene affecting body weight, abdominal circumference, and fur length in Arctic foxes, whereas variations in the leptin receptor mainly affect carcass weight and guard hair. The marker loci identified in this study can be used to assist in the selection of Arctic foxes for breeding to raise the production performance of this species.

  5. 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.

  6. Folate and One-Carbon Metabolism Gene Polymorphisms and Their Associations With Oral Facial Clefts

    PubMed Central

    Boyles, Abee L.; Wilcox, Allen J.; Taylor, Jack A.; Meyer, Klaus; Fredriksen, Åse; Ueland, Per Magne; Drevon, Christian A.; Vollset, Stein Emil; Lie, Rolv Terje

    2008-01-01

    Folate metabolism plays a critical role in embryonic development. Prenatal folate supplementation reduces the risk of neural tube defects and probably oral facial clefts. Previous studies of related metabolic genes have associated polymorphisms in cystathionine-beta-synthase (CBS) and 5,10-methylenetetrahydrofolate reductase (MTHFR) with cleft risk. We explored associations between genes related to one-carbon metabolism and clefts in a Norwegian population-based study that included 362 families with cleft lip with or without cleft palate (CL/P) and 191 families with cleft palate only (CPO). We previously showed a 39% reduction in risk of CL/P with folic acid supplementation in this population. In the present study we genotyped 12 polymorphisms in nine genes related to one-carbon metabolism and looked for associations of clefting risk with fetal polymorphisms, maternal polymorphisms, as well as parent-of-origin effects, using combined likelihood-ratio tests (LRT). We also stratified by maternal periconceptional intake of folic acid (>400 μg) to explore gene-exposure interactions. We found a reduced risk of CL/P with mothers who carried the CBS C699T variant (rs234706); relative risk was 0.94 with one copy of the T allele (95% CI 0.63-1.4) and 0.50 (95% CI 0.26-0.96) with two copies (P = 0.008). We found no evidence of interaction of this variant with folate status. We saw no evidence of risk from the MTHFR C677T variant (rs1801133) either overall or after stratifying by maternal folate intake. No associations were found between any of the polymorphisms and CPO. Genetic variations in the nine metabolic genes examined here do not confer a substantial degree of risk for clefts. Published 2008 Wiley-Liss, Inc.† PMID:18203168

  7. Genetic Polymorphisms of Metastasis Suppressor Gene NME1 and Breast Cancer Survival

    PubMed Central

    Qu, Shimian; Long, Jirong; Cai, Qiuyin; Shu, Xiao-Ou; Cai, Hui; Gao, Yu-Tang; Zheng, Wei

    2009-01-01

    Purpose Ample evidence supports an important role of tumor metastasis suppressor genes in cancer metastatic processes. We evaluated the association of genetic polymorphisms of tumor metastasis suppressor gene NME1 with breast cancer prognosis in a follow-up study of patients with primary breast cancer and further investigated the functions of these polymorphisms. Experimental Design NME1 genotypes were analyzed in a cohort of 1134 breast cancer patients recruited as part of the Shanghai Breast Cancer Study who were followed for a median of 7.1 years. In vitro biochemical analyses were carried out to examine the function of NME1 gene polymorphisms. Results Single nucleotide polymorphisms (SNPs) in the promoter region of the NME1 gene were found to be associated with breast cancer prognosis. Patients carrying the C allele in rs16949649 were associated with higher breast cancer-specific mortality (HR =1.4, 95% CI =1.1–1.9) as compared to those carrying the wild-type allele, and the association was more evident in patients with an early stage cancer (HR=1.7, 95% CI =1.2–2.5). SNP rs2302254 was also associated with breast cancer prognosis, and the association was statistically significant for the risk of breast cancer relapse, metastasis, and death (HR=1.3, 95% CI, 1.0–1.6). In vitro biochemical analyses showed that minor alleles in rs2302254 and rs3760468, which is in strong linkage disequilibrium with rs16949646, altered nuclear proteins binding capacity and reduced NME1 promoter activity, supporting the results from an association study of these SNPs with breast cancer survival. Conclusion Promoter polymorphisms in the NME1 gene may alter its expression and influence breast cancer survival. PMID:18676749

  8. Tumor necrosis factor-alpha gene polymorphisms and susceptibility to ischemic heart disease

    PubMed Central

    Zhang, Peng; Wu, Xiaomei; Li, Guangxiao; He, Qiao; Dai, Huixu; Ai, Cong; Shi, Jingpu

    2017-01-01

    Abstract Background: A number of studies had reported the association between tumor necrosis factor-alpha (TNF-α) gene polymorphisms and ischemic heart disease (IHD) risk. However, the results remained controversial. Therefore, we performed a systematic review with multiple meta-analyses to provide the more precise estimations of the relationship. Methods: We systematically searched electronic databases (PubMed, the Web of Science, EMBASE, Medline, Chinese National Knowledge Infrastructure, WanFang and ChongQing VIP Database) for relevant studies published up to February 2017. The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for assessing the association. The present meta-analysis was performed using STATA 12.0 software. Results: In total, 45 articles with 17,375 cases and 15,375 controls involved were included. Pooled ORs revealed a significant association between TNF-α −308G/A gene polymorphism and IHD (A vs. G: OR = 1.22, 95% CI = 1.10–1.35; (AA + GA) vs. GG: OR = 1.18, 95% CI = 1.03–1.36; (AA vs. (GA+GG): OR = 1.37, 95% CI = 1.08–1.75)), indicating that the TNF-α −308A allele might be an important risk factor for IHD. No association between other TNF-α gene polymorphisms and susceptibility to IHD were observed. No publication bias were found. Sensitivity analyses indicated that our results were stable. Conclusion: The present study indicated a possible association between the TNF-α −308G/A gene polymorphism and IHD risk. However, evidence was limited to confirm the role of TNF-α −238G/A, −857C/T, −863C/A, −1031T/C and other TNF-α gene polymorphisms in the risk of IHD. PMID:28383437

  9. Study on the correlation between KCNJ11 gene polymorphism and metabolic syndrome in the elderly.

    PubMed

    Jiang, Fan; Liu, Ning; Chen, Xiao Zhuang; Han, Kun Yuan; Zhu, Cai Zhong

    2017-09-01

    The aim of the study was to examine the correlation between KCNJ11 gene polymorphism and metabolic syndrome in elderly patients. From January 2014 to January 2015, 54 elderly patients with metabolic syndrome were enrolled in this study as the observation group. During the same period, 46 healthy elderly individuals were enrolled in this study as the control group. KCNJ11 gene polymorphism (rs28502) was analyzed using polymerase chain reaction-restriction fragment length polymorphism. The expression levels of mRNA in different genotypes were detected using FQ-PCR. ELISA was used to evaluate the KCNJ11 protein expression in different genotypes. KCNJ11 gene polymorphism and metabolic syndrome was studied by measuring the blood pressure levels in patients with different genotypes. Three genotypes of KCNJ11 gene in rs28502 were CC, CT and TT. The CC, CT and TT genotype frequencies in healthy population were 8.5, 9.2 and 82.2%, respectively, while the genotype frequencies in patients with metabolic syndrome were 42.4, 49.8 and 7.8%, respectively. There were significant differences between groups (P≤0.05). However, the genotype frequencies of C/T in healthy individuals and metabolic syndrome patients were 35.3 and 38.3%, respectively. There were no significant differences between groups (P>0.05). FQ-PCR results showed that the KCNJ11 mRNA expression levels in the control and observation groups had no significant differences (P>0.05). However, the results obtained from ELISA analysis revealed that KCNJ11 protein expression level in the observation group was significantly higher than that in the control group (P<0.05). In conclusion, KCNJ11 gene polymorphism is associated with metabolic syndrome in the elderly. Elderly patients with the CC and TT genotypes are more likely to develop metabolic syndrome.

  10. The relation of serotonin-related gene and COMT gene polymorphisms with criminal behavior in schizophrenic disorder.

    PubMed

    Koh, Kyung Bong; Choi, Eun Hee; Lee, Young-joon; Han, Mooyoung; Choi, Sang-Sup; Kim, So Won; Lee, Min Goo

    2012-02-01

    It has been suggested that patients with schizophrenia might be involved in criminal behavior, such as homicidal and violent behavior. However, the relationship between criminal behavior and genes in patients with schizophrenia has not been clearly elucidated. The objective of this study was to examine the relation between criminal behavior and serotonin-related gene or catechol-O-methyltransferase (COMT) gene polymorphisms in patients with schizophrenia. Serotonin-related and COMT polymorphic markers were assessed by using single nucleotide polymorphism (SNP) genotyping. Ninety-nine crime-related inpatients with schizophrenia (57 homicidal and 42 nonhomicidal violent) and 133 healthy subjects were enrolled between October 2005 and May 2008. Diagnoses were made according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. The genotype frequencies of tryptophan hydroxylase-1 (TPH1) A218C and COMT V158M were compared between groups. The TPH1 CC genotype had 2.7-fold higher odds of crime-related schizophrenia compared with A-carrier genotype after the analysis was controlled for sex and age (OR, 2.69; 95% CI, 1.22 - 5.91; P = .01). In addition, the TPH1 CC genotype had 3.4-fold higher odds of homicidal schizophrenia compared with A-carrier genotype after the analysis was controlled for sex and age (OR, 3.38; 95% CI, 1.40 - 8.18; P = .007). However, no significant differences were found in the frequencies of genotype of COMT polymorphism between criminal schizophrenics and healthy subjects, nor were any significant differences found between nonhomicidal schizophrenics and healthy subjects. These results indicate that the TPH1 CC recessive genotype is likely to be a genetic risk factor for criminal behavior, especially homicidal behavior in patients with schizophrenia. However, COMT gene polymorphisms were not associated with criminal behavior in schizophrenic patients. © Copyright 2012 Physicians Postgraduate Press, Inc.

  11. MAOA and TNF-β gene polymorphisms are associated with photophobia but not osmophobia in patients with migraine.

    PubMed

    Ishii, Masakazu; Usami, Shino; Hara, Hajime; Imagawa, Atsuko; Masuda, Yutaka; Shimizu, Shuniichi

    2014-06-01

    Photophobia and osmophobia are typical symptoms associated with migraine, but the contributions of gene polymorphisms to these symptoms are not fully elucidated. We investigated whether the gene polymorphisms are involved in photophobia and osmophobia in patients with migraine. Ninety-one migraine patients and 119 non-headache healthy volunteers were enrolled. The 12 gene polymorphisms were determined by polymerase-chain-reaction (PCR) and PCR restriction-fragment-length polymorphism analysis. Photophobia and osmophobia were observed in 49 (54%) and 31 patients (34%), respectively. Distributions of monoamine oxidase A (MAOA) T941G and tumour necrosis factor-β (TNF-β) G252A polymorphisms were significantly different between patients with photophobia and controls. However, no gene polymorphism differences were observed between patients with osmophobia and controls. The MAOA T941G and TNF-β G252A gene polymorphisms appear to contribute to photophobia but not to osmophobia. We propose that different gene polymorphisms are responsible for photophobia and osmophobia symptoms during migraine.

  12. A pilot study assessing the association between paraoxonase 1 gene polymorphism and prostate cancer.

    PubMed

    Uluocak, Nihat; Atılgan, Doğan; Parlaktaş, Bekir Süha; Erdemir, Fikret; Ateş, Ömer

    2017-09-01

    We aimed to show the relationship between paraoxonase 1 (PON1) gene polymorphism and the development of prostate cancer (PCa). We investigated the association of single nuclotide polymorphisms of PON1 enzyme with the development of PCa risk. A total of 147 male patients were divided into PCa, and control groups. The control group was also divided into two subgroups according to serum prostate specific antigen (PSA) levels as non PCa-high PSA (>4 ng/mL) and non PCa-low PSA (≤4 ng/mL) groups. The mean ages of the patients were 64.81 years, 63.27 years and 64.22 years in PCa group, non PCa-low PSA and non PCa -high PSA groups, respectively. The mean PSA levels were 10.9 ng/mL, 1.16 ng/mL and 6.63 ng/mL for PCa group, non PCa -low PSA and non PCa -high PSA groups, respectively. In terms of PON1 polymorphisms and allele frequencies, there were no statistically significant differences between PCa and control groups. There was not a statistically significant difference between PCa and non PCa-high PSA groups as for genotypic and allelic frequencies. As a result of this small sample sized hypothetical study of polymorphism, a relationship could not be detected between PCa development and PON1 gene polymorphism. According to the results of this preliminary study, it is thought that more comprehensive future studies are necessary to clarify the possible role of PON1 gene polymorphism in the etiology of PCa.

  13. Analysis of vitamin D receptor gene polymorphisms in patients with chronic periodontitis.

    PubMed

    Gunes, Sezgin; Sumer, A Pinar; Keles, Gonca Cayir; Kara, Nurten; Koprulu, Hulya; Bagci, Hasan; Bek, Yuksel

    2008-01-01

    Genetic polymorphisms in the vitamin D receptor (VDR) gene are related to bone mineral density, bone turnover, and diseases with bone loss. Alveolar bone loss is a key feature in periodontitis. The aim of this study was to determine whether severe generalized chronic periodontitis (CP) in a Turkish population was associated with polymorphisms in the VDR gene. Samples of venous blood and DNA were obtained from 72 patients with severe generalized chronic periodontitis and 102 healthy controls. The polymorphic regions were amplified using PCR followed by digestion with restriction enzymes BsmI A/G(rs1544410), ApaI G/T(rs11168271), TaqI T/C(rs731236), and analyzed electrophoretically. Genotype and allele frequencies were calculated. There were no statistically significant differences in the frequencies of VDR BsmI, ApaI, TaqI genotypes between the CP patients and healthy controls. The GTT haplotype, constructed from the three adjacent restriction fragment length polymorphisms was found to be over-represented among CP cases. This corresponded an OR of 2.4 (95% confidence interval, 1.12-5.18) for heterozygous carriers and 2.27 (95% confidence interval, 0.95-5.4) for homozygous carrier of the risk haplotype. The present findings indicated that BsmI, ApaI, TaqI polymorphisms of the VDR gene were not associated with the severe generalized CP in the studied Turkish patients. Moreover, the VDR genotypes based on haplotype analysis may be associated with chronic periodontitis. In the future, diagnostic periodontal risk assessments like polymorphisms may be useful in detection of individuals susceptible for periodontitis.

  14. Polymorphisms in the phosducin (PDC) gene on chromosome 1q25-32

    SciTech Connect

    Humphries, P.; Mansergh, F.C.; Farrar, G.J.

    1994-09-01

    Phosducin (33 kDa protein or MEKA) is a principal water-soluble phosphoprotein in the rod and cone photoreceptor cells and pinealocytes. This protein modulates the phototransduction cascade by binding to the beta and gamma subunit complexes of transducin. The PDC gene has been mapped to 1q25-32, the region of linkage of two hereditary retinal degenerative disorders; autosomal dominant juvenile-onset open-angle glaucoma and one form of autosomal recessive RP. Using previously published sequence data, PCR primers were designed to amplify the coding and 5{prime} flanking regions of the PDC gene. Direct sequencing revealed three polymorphisms in the 5{prime} flanking region, two ofmore » which were in regions highly homologous between humans and mice. Analysis of the polymorphisms was then extended to larger population samples using SSCPE and denaturing gel analysis. The first polymorphism PDC1 resulted from an insertion of a G residue at position -653/4. Allele frequencies were determined to be 0.51 (insG) and 0.49 (normal) giving a PIC value of 0.50. A deletion of a T residue at position -488 was the basis of the PDC2 polymorphism with allele frequencies of 0.88 (normal) and 0.12 (delT) and a PIC value of 0.21. Interestingly, the allele with an inserted G residue in PDC1 always segregrated with the deleted T allele in PDC2. The third polymorphism PDC3 was caused by a T or G residue at position -1083. Allele frequencies of 0.26 (G residue) and 0.74 (T residue) were determined from an analysis of 80 individuals with an overall PIC value of 0.39. The identification of these three polymorphisms in the PDC gene will be useful for future genetic linkage studies of chromosome 1q in inherited retinopathies.« less

  15. Impact of CCL4 gene polymorphisms and environmental factors on oral cancer development and clinical characteristics.

    PubMed

    Lien, Ming-Yu; Lin, Chiao-Wen; Tsai, Hsiao-Chi; Chen, Yng-Tay; Tsai, Ming-Hsui; Hua, Chun-Hung; Yang, Shun-Fa; Tang, Chih-Hsin

    2017-05-09

    In Taiwan, oral cancer has causally been associated with environmental carcinogens. CCL4 (C-C chemokine ligand 4), a macrophage inflammatory protein with a key role in inflammation and immune-regulation, was implicated in carcinogenesis by facilitating instability in the tumor environment. The purpose of this study was to identify gene polymorphisms of CCL4 specific to patients with oral squamous cell carcinoma (OSCC) susceptibility and clinicopathological characteristics. A total of 2,053 participants, including 1192 healthy people and 861 patients with oral cancer, were recruited for this study. Three single-nucleotide polymorphisms (SNPs) of the CCL4 gene were analyzed by a real-time PCR. We found that the T/T homozygotes of CCL4 rs1634507 G/T polymorphism and the GG haplotype of 2 CCL4 SNPs (rs1634507 and rs10491121) combined were associated with oral-cancer susceptibility. In addition, TA haplotype significantly decreased the risks for oral cancer by 0.118 fold. Among 1420 smokers, CCL4 polymorphisms carriers with the betel-nut chewing habit had a 15.476-20.247-fold greater risk of having oral cancer compared to CCL4 wild-type (WT) carriers without the betel-nut chewing habit. Finally, patients with oral cancer who had A/G heterozygotes of CCL4 rs10491121 A/G polymorphism showed a lower risk for an advanced tumor size (> T2) (p=0.046), compared to those patients with AA homozygotes. Our results suggest that the CCL4 rs1634507 SNP have potential predictive significance in oral carcinogenesis. Gene-environment interactions of CCL4 polymorphisms might influence oral-cancer susceptibility. CCL4 rs10491121 may be a factor to predict the tumor size in OSCC patients.

  16. A pilot study assessing the association between paraoxonase 1 gene polymorphism and prostate cancer

    PubMed Central

    Uluocak, Nihat; Atılgan, Doğan; Parlaktaş, Bekir Süha; Erdemir, Fikret; Ateş, Ömer

    2017-01-01

    Objective We aimed to show the relationship between paraoxonase 1 (PON1) gene polymorphism and the development of prostate cancer (PCa). Material and methods We investigated the association of single nuclotide polymorphisms of PON1 enzyme with the development of PCa risk. A total of 147 male patients were divided into PCa, and control groups. The control group was also divided into two subgroups according to serum prostate specific antigen (PSA) levels as non PCa-high PSA (>4 ng/mL) and non PCa-low PSA (≤4 ng/mL) groups. Results The mean ages of the patients were 64.81 years, 63.27 years and 64.22 years in PCa group, non PCa-low PSA and non PCa –high PSA groups, respectively. The mean PSA levels were 10.9 ng/mL, 1.16 ng/mL and 6.63 ng/mL for PCa group, non PCa –low PSA and non PCa –high PSA groups, respectively. In terms of PON1 polymorphisms and allele frequencies, there were no statistically significant differences between PCa and control groups. There was not a statistically significant difference between PCa and non PCa-high PSA groups as for genotypic and allelic frequencies. As a result of this small sample sized hypothetical study of polymorphism, a relationship could not be detected between PCa development and PON1 gene polymorphism. Conclusion According to the results of this preliminary study, it is thought that more comprehensive future studies are necessary to clarify the possible role of PON1 gene polymorphism in the etiology of PCa. PMID:28861298

  17. Association study between GAS6 gene polymorphisms and risk of preeclampsia in Chinese population.

    PubMed

    Ye, Liyan; Guan, Linbo; Fan, Ping; Liu, Xinghui; Liu, Rui; Chen, Jinxin; Zhu, Yue; Wei, Xing; Liu, Yu; Bai, Huai

    2017-04-01

    Preeclampsia is a pregnancy-specific disorder associated with pro-inflammatory and pro-thrombotic events. The growth arrest-specific 6 (GAS6) has been implicated in systemic inflammation and coagulation. Common genetic polymorphisms of GAS6 gene have previously been reported. The aim of this study was to investigate the association of GAS6 gene polymorphisms with the risk of preeclampsia in Chinese subjects. The case-control population consists of 551 subjects. The genotyping of the single-nucleotide polymorphisms of GAS6 gene, GAS6 834 +7G/A(rs8191974) and +1332C/T (rs1803628), was carried out on genomic DNA using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) analysis. There were significant differences in the +1332C/T genotype and allele frequencies between the patients with preeclampsia and the controls (P=0.03 and 0.02, respectively). The +1332 TT genotype was found to be protective from the development of preeclampsia (odds ratios 0.271, 95% confidence interval 0.077-0.953; P=0.03). Further analysis showed that the TT genotype of the GAS6 +1332C/T conferred a risk of severe preeclampsia (OR=0.597, 95% confidence interval 0.416-0.855; P=0.01). However, there were no differences in the 834+7G/A genotype and allele frequencies between the patients with preeclampsia and the controls. Our data suggest that a TT genotype at +1332C/T polymorphism might be associated with decreased risk for preeclampsia, but the 834+7G/A polymorphism is not associated with the disorder, in the Chinese population. Copyright © 2017. Published by Elsevier B.V.

  18. MAOA, MTHFR, and TNF-β genes polymorphisms and personality traits in the pathogenesis of migraine.

    PubMed

    Ishii, Masakazu; Shimizu, Shunichi; Sakairi, Yuki; Nagamine, Ayumu; Naito, Yuika; Hosaka, Yukiko; Naito, Yuko; Kurihara, Tatsuya; Onaya, Tomomi; Oyamada, Hideto; Imagawa, Atsuko; Shida, Kenji; Takahashi, Johji; Oguchi, Katsuji; Masuda, Yutaka; Hara, Hajime; Usami, Shino; Kiuchi, Yuji

    2012-04-01

    Migraine is a multifactorial disease with various factors, such as genetic polymorphisms and personality traits, but the contribution of those factors is not clear. To clarify the pathogenesis of migraine, the contributions of genetic polymorphisms and personality traits were simultaneously investigated using multivariate analysis. Ninety-one migraine patients and 119 non-headache healthy volunteers were enrolled. The 12 gene polymorphisms analysis and NEO-FFI personality test were performed. At first, the univariate analysis was performed to extract the contributing factors to pathogenesis of migraine. We then extracted the factors that independently contributed to the pathogenesis of migraine using multivariate stepwise logistic regression analysis. Using the multivariate analysis, three gene polymorphisms including monoamine oxidase A (MAOA) T941G, methylenetetrahydrofolate reductase (MTHFR) C677T, and tumor necrosis factor beta (TNF-β) G252Α, and the neuroticism and conscientiousness scores in NEO-FFI were selected as significant factors that independently contributed to the pathogenesis of migraine. Their odds ratios were 1.099 (per point of neuroticism score), 1.080 (per point of conscientiousness score), 2.272 (T and T/T or T/G vs G and G/G genotype of MAOA), 1.939 (C/T or T/T vs C/C genotype of MTHFR), and 2.748 (G/A or A/A vs G/G genotype of TNF-β), respectively. We suggested that multiple factors, such as gene polymorphisms and personality traits, contribute to the pathogenesis of migraine. The contribution of polymorphisms, such as MAOA T941G, MTHFR C677T, and TNF-β G252A, were more important than personality traits in the pathogenesis of migraine, a multifactorial disorder.

  19. Q192R polymorphism in the PON1 gene and familial hypercholesterolemia in a Saudi population.

    PubMed

    Alharbi, Khalid Khalaf; Alnbaheen, May Salem; Alharbi, Fawiziah Khalaf; Hasanato, Rana M; Khan, Imran Ali

    2017-01-01

    Familial hypercholesterolemia (FH) is an autosomal dominant condition characterized by abnormal levels of low-density lipoprotein (LDL) in the blood. FH is a risk factor for atherosclerosis and cardiovascular disease. The relationship between the paraoxonase 1 (PON1) gene, atherosclerosis and coronary artery disease has not been studied in Saudi patients. To investigate the genetic associations of the Q192R polymorphism in the PON1 gene with FH in Saudi patients. Case-control study. Tertiary care center, Riyadh. Two hundred Saudi patients were enrolled in this study, including 100 patients with FH and 100 healthy controls, during the period from January 2012 to March 2013. Serum was separated from coagulated blood (3 mL) and used for analysis of lipid profiles. Genomic DNA was isolated from anticoagulant-treated blood (2 mL). Genotyping for the Q192R polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism analysis, followed by 3% agarose gel electrophoresis. The strength of association between the Q192R polymorphism and FH in the Saudi population. We confirmed that QR versus QQ (odds ratio [OR]: 1.55; 95% confidence interval [CI]: 1.05-3.43; P=.03), QR+RR versus QQ (OR: 1.98; 95% CI: 1.13-3.49; P=.01), and R versus Q (OR: 1.68; 95% CI: 1.09- 2.59; P=.01) in the Q192R polymorphism were associated with FH in the Saudi population. In conclusion, the Q192R polymorphism in the PON1 gene is associated with FH in the Saudi population. Our results confirmed that the R allele, QR, and dominant model genotypes were associated with FH. Only a single variant (Q192R) was analyzed, and the medical and family histories of the patients were not known.

  20. Impact of CCL4 gene polymorphisms and environmental factors on oral cancer development and clinical characteristics

    PubMed Central

    Lien, Ming-Yu; Lin, Chiao-Wen; Tsai, Hsiao-Chi; Chen, Yng-Tay; Tsai, Ming-Hsui; Hua, Chun-Hung; Yang, Shun-Fa; Tang, Chih-Hsin

    2017-01-01

    In Taiwan, oral cancer has causally been associated with environmental carcinogens. CCL4 (C-C chemokine ligand 4), a macrophage inflammatory protein with a key role in inflammation and immune-regulation, was implicated in carcinogenesis by facilitating instability in the tumor environment. The purpose of this study was to identify gene polymorphisms of CCL4 specific to patients with oral squamous cell carcinoma (OSCC) susceptibility and clinicopathological characteristics. A total of 2,053 participants, including 1192 healthy people and 861 patients with oral cancer, were recruited for this study. Three single-nucleotide polymorphisms (SNPs) of the CCL4 gene were analyzed by a real-time PCR. We found that the T/T homozygotes of CCL4 rs1634507 G/T polymorphism and the GG haplotype of 2 CCL4 SNPs (rs1634507 and rs10491121) combined were associated with oral-cancer susceptibility. In addition, TA haplotype significantly decreased the risks for oral cancer by 0.118 fold. Among 1420 smokers, CCL4 polymorphisms carriers with the betel-nut chewing habit had a 15.476–20.247-fold greater risk of having oral cancer compared to CCL4 wild-type (WT) carriers without the betel-nut chewing habit. Finally, patients with oral cancer who had A/G heterozygotes of CCL4 rs10491121 A/G polymorphism showed a lower risk for an advanced tumor size (> T2) (p=0.046), compared to those patients with AA homozygotes. Our results suggest that the CCL4 rs1634507 SNP have potential predictive significance in oral carcinogenesis. Gene-environment interactions of CCL4 polymorphisms might influence oral-cancer susceptibility. CCL4 rs10491121 may be a factor to predict the tumor size in OSCC patients. PMID:28404909

  1. Association of Adiponectin rs1501299 and rs266729 Gene Polymorphisms With Nonalcoholic Fatty Liver Disease

    PubMed Central

    Hashemi, Mohammad; Hanafi Bojd, Hamideh; Eskandari Nasab, Ebrahim; Bahari, Ali; Hashemzehi, Noor Allah; Shafieipour, Sara; Narouie, Behzad; Taheri, Mohsen; Ghavami, Saeid

    2013-01-01

    Background Genetic and environmental factors are important for the development of nonalcoholic fatty liver disease (NAFLD). Adiponectin is a white and brown adipose tissue hormone, and have been found to play essential roles in the regulation of energy homoeostasis. Recent reports have identified a possible role of adiponectin in NAFLD via PPARγ pathway. Objectives The present study was designed to find out the impact of adiponectin rs1501299 (276G/T) and rs266729 (-11377C/G) gene polymorphisms in NAFLD. Patients and Methods Eighty-three patients with diagnosis of NAFLD, and 93 healthy subjects were included in the study. Tetra ARMS-PCR was designed to detect single nucleotide polymorphisms. Results A significant difference was found between NAFLD and control group regarding the rs266729 polymorphism (χ2 = 7.35, P = 0.025). The rs266729 polymorphism increased the risk of NAFLD in codominant (CC vs. CG: OR = 2.18, 95% CI = 1.16 - 4.12, P = 0.016) and dominant (CC vs. CG/GG: OR = 2.31, 95% CI = 1.25 - 4.27; P = 0.008) inheritance tested models. The G allele increased the risk of NAFLD (OR = 1.63, 95% CI = 1.03 - 2.57, P = 0.037) in comparison with C allele. No significant difference was found between the groups concerning adiponectin rs1501299 gene polymorphism (χ2 = 0.70, P = 0.697). Conclusions adiponectin rs266729 polymorphism might be a candidate gene, which determines the susceptibility to NAFLD. Larger studies are necessary to confirm these findings in various populations. PMID:23922565

  2. Polymorphisms of the lipoprotein lipase gene as genetic markers for stroke in colombian population: a case control study.

    PubMed

    Velásquez Pereira, Leydi Carolina; Vargas Castellanos, Clara Inés; Silva Sieger, Federico Arturo

    2016-12-30

    To analyze if there is an association between the presence of polymorphisms in the LPL gene (rs320, rs285 and rs328) with development of acute ischemic stroke in Colombian population. In a case control design, 133 acute ischemic stroke patients (clinical diagnosis and x-ray CT) and 269 subjects without stroke as controls were studied. PCR -RFLP technique was used to detect rs320, rs285 and rs328 polymorphisms in the LPL gene. In the present research was not found any association between any of the LPL gene polymorphism and acute ischemic stroke in the population studied; the allele and genotypic frequencies of the studied polymorphisms were similar in cases and controls and followed the Hardy-Weinberg equilibrium. The study was approved by the IRB and each subject signed the informed consent. LPL gene polymorphisms are not genetic markers for the development of stroke in the Colombian sample used.

  3. Genetic analysis of interleukin 18 gene polymorphisms in alopecia areata.

    PubMed

    Celik, Sumeyya Deniz; Ates, Omer

    2018-06-01

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

  4. Associations between single nucleotide polymorphisms in multiple candidate genes and body weight in rabbits

    PubMed Central

    El-Sabrout, Karim; Aggag, Sarah A.

    2017-01-01

    Aim: In this study, we examined parts of six growth genes (growth hormone [GH], melanocortin 4 receptor [MC4R], growth hormone receptor [GHR], phosphorglycerate mutase [PGAM], myostatin [MSTN], and fibroblast growth factor [FGF]) as specific primers for two rabbit lines (V-line, Alexandria) using nucleotide sequence analysis, to investigate association between detecting single nucleotide polymorphism (SNP) of these genes and body weight (BW) at market. Materials and Methods: Each line kits were grouped into high and low weight rabbits to identify DNA markers useful for association studies with high BW. DNA from blood samples of each group was extracted to amplify the six growth genes. SNP technique was used to study the associate polymorphism in the six growth genes and marketing BW (at 63 days) in the two rabbit lines. The purified polymerase chain reaction products were sequenced in those had the highest and lowest BW in each line. Results: Alignment of sequence data from each group revealed the following SNPs: At nucleotide 23 (A-C) and nucleotide 35 (T-G) in MC4R gene (sense mutation) of Alexandria and V-line high BW. Furthermore, we detected the following SNPs variation between the two lines: A SNP (T-C) at nucleotide 27 was identified by MC4R gene (sense mutation) and another one (A-C) at nucleotide 14 was identified by GHR gene (nonsense mutation) of Alexandria line. The results of individual BW at market (63 days) indicated that Alexandria rabbits had significantly higher BW compared with V-line rabbits. MC4R polymorphism showed significant association with high BW in rabbits. Conclusion: The results of polymorphism demonstrate the possibility to detect an association between BW in rabbits and the efficiency of the used primers to predict through the genetic specificity using the SNP of MC4R. PMID:28246458

  5. [Relationship between interleukin-17A gene polymorphisms and the susceptibility to childhood asthma].

    PubMed

    Zhong, Fang-Fang; Zou, Yan; Liu, Chun-Yan; Liu, Wen-Jun

    2016-12-01

    To explore the relationship between polymorphisms of interleukin-17A (IL-17A) gene promoter (-197G/A and -692C/T) and the susceptibility to childhood asthma, to further identify the candidate genes for asthma, and to provide a basis for early prevention of asthma in high-risk children. Sixty-five outpatients or inpatients with childhood asthma between August 2013 and August 2015 were assigned to asthma group. Seventy healthy children within the same period were assigned to control group. Using peripheral venous blood from the two groups, PCR with sequence-specific primers was carried out to determine single nucleotide polymorphisms at positions -197G/A and -692C/T in IL-17A gene promoter. A statistical analysis was used to evaluate differences in genotype and allele frequencies between the two groups. Compared with the control group, the asthma group had significantly higher frequencies of TT genotype (29% vs 16%; P=0.012) and T allele (52% vs 42%; P=0.039) at position -692C/T of IL-17A gene. Children with T allele had 1.413-fold higher risk of childhood asthma than those with C allele (OR=1.413, 95%CI: 1.015-1.917). There were no significant differences in genotype and allele frequencies at position -197G/A in IL-17A gene between the two groups (p>0.05). Polymorphisms at position -692C/T in IL-17A gene promoter is associated with the susceptibility to childhood asthma. Children with -692T allele are more susceptible to childhood asthma. There is no significant relationship between polymorphisms at position -197G/A in IL-17A gene promoter and the susceptibility to childhood asthma.

  6. 5-HT2A receptor gene polymorphisms in Croatian subjects with autistic disorder.

    PubMed

    Hranilovic, Dubravka; Blazevic, Sofia; Babic, Marina; Smurinic, Maja; Bujas-Petkovic, Zorana; Jernej, Branimir

    2010-08-15

    Disturbances in the expression/function of the 5-HT2A receptor are implicated in autism. The association of the 5-HT2A receptor gene with autism was studied in the Croatian population. Distribution frequencies for alleles, genotypes and haplotypes of -1438 A/G and His452Tyr polymorphisms were compared in samples of 103 autistic and 214 control subjects. Significant overrepresentation of the G allele and the GG genotype of the -1438 A/G polymorphism was observed in group of autistic subjects, supporting the possible involvement of the 5-HT2A receptor in the development of autism. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  7. [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.

  8. A polymorphism in the bovine gamma-S-crystallin gene revealed by allele-specific amplification.

    PubMed

    Kemp, S J; Maillard, J C; Teale, A J

    1993-04-01

    A polymorphism was detected in the 3' untranslated region of the bovine gamma-S-crystallin gene by direct sequencing of polymerase chain reaction (PCR) products from genomic DNA of an N'Dama bull and a Boran cow. A set of three PCR primers was designed to detect this difference and thus give allele-specific amplification. The two allele-specific primers differ in length by 20 nucleotides so that the allelic products may be distinguished by simple agarose gel electrophoresis following a single PCR reaction. This provides a simple and rapid assay for this polymorphism.

  9. Association of BDNF gene polymorphisms with schizophrenia and clinical symptoms in a Chinese population.

    PubMed

    Li, Wenjun; Zhou, Na; Yu, Qiong; Li, Xiaokun; Yu, Yaqin; Sun, Shilong; Kou, Changgui; Chen, Da Chun; Xiu, Mei Hong; Kosten, Thomas R; Zhang, Xiang Yang

    2013-09-01

    The neurodevelopmental hypothesis is well established in schizophrenia. Accumulating evidence has shown that BDNF may be involved in the pathogenesis of schizophrenia. This study aimed to investigate the potential association of BDNF gene polymorphisms with susceptibility to schizophrenia and with the psychopathological symptoms in patients with schizophrenia in a Han Chinese population. Three polymorphisms (rs6265, rs12273539, and rs10835210) of the BDNF gene were analyzed in a case-control study of 709 Han Chinese individuals (375 patients and 334 controls). The patients' psychopathology was assessed using the positive and negative syndrome scale (PANSS). We found no significant differences in the genotype and allele distributions of all three polymorphisms between the patient and control groups; however, we found a trend toward to significant overall difference in the estimated haplotype frequencies, with more frequent haplotype ATC of rs6265-rs12273539-rs10835210 in the schizophrenic patients than in controls (P = 0.027). The quantitative trait analysis by the UNPHASED program showed significant associations between the rs6265 (A)-rs12273539 (C)-rs10835210 (A) haplotype and negative symptom scores from the PANSS (x(2)  = 5.79, P = 0.016). Our findings suggest that the BDNF gene polymorphisms may play a small effect on susceptibility to schizophrenia, but may contribute to the negative symptoms of the disease. Copyright © 2013 Wiley Periodicals, Inc.

  10. Spontaneous abortion and functional polymorphism (Val16Ala) in the manganese SOD gene.

    PubMed

    Eskafi Sabet, E; Salehi, Z; Khodayari, S; Sabouhi Zarafshan, S; Zahiri, Z

    2015-02-01

    Spontaneous abortion is the most common complication of early pregnancy. Genetic factors have been hypothesised to play a role in spontaneous abortion. Since it is possible that the balance of oxidants and antioxidants can be affected by different genetic variants, gene polymorphisms have been proposed as a susceptibility factor that increases the chance of miscarriage. Manganese superoxide dismutase is an important antioxidant enzyme encoded by manganese superoxide dismutase (MnSOD) gene. The aim of this experiment was to assess whether Val16Ala polymorphism of MnSOD gene is associated with miscarriage in northern Iran. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for genotyping. Statistical analyses were conducted using the χ(2)-test. The genetic distributions did not differ significantly between cases and controls, however slightly more Val/Val genotypes were found among the patients compared with control subjects (p = 0.059). No correlation was observed between susceptibility to abortion and MnSOD Val16Ala polymorphism. Larger population-based studies are needed for clarifying the relationship between abortion and MnSOD genotypes.

  11. Polymorphisms of the TLR4 gene and risk of gastric cancer.

    PubMed

    Huang, Lina; Yuan, Kexin; Liu, Jingjing; Ren, Xiyun; Dong, Xiaoqun; Tian, Wenjing; Jia, Yunhe

    2014-03-01

    Toll-like receptor 4 (TLR4) is an important lipo-polysaccharide (LPS) receptor in gastric epithelial cell signaling transduction and plays critical roles in the development and progression of gastric cancer (GC). We investigated the effects of TLR4 gene polymorphisms and gene-environmental interactions on the risk of GC in Northeastern China. We genotyped two single-nucleotide polymorphisms (SNPs) in TLR4 (rs10116253 and rs1927911) in 217 GC patients and 294 cancer-free controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Odds ratio (OR) and 95% confidence intervals (CIs) were estimated by unconditional logistic-regression models. Individuals carrying CC genotype of rs10116253 and TT genotype of rs1927911 had a significantly decreased risk of GC (adjusted OR=0.33, 95% CI 0.18-0.60, P<0.001 and adjusted OR=0.37, 95% CI 0.21-0.67, P=0.001 respectively), compared with TT genotype of rs10116253 and CC genotype of rs1927911. In addition, the SNP effects were additive to the effects of some known environmental factors without any interaction between them in the susceptibility to GC. Our data suggested that TLR4 gene polymorphisms may be associated with a decreased risk of GC in Chinese population. And these SNPs and their combined effects with environmental factors may be associated with the risk of GC. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. [K198N polymorphism in the EDN1 gene in patients with pulmonary arterial hypertension].

    PubMed

    Pousada, Guillermo; Baloira, Adolfo; Vilariño, Carlos; Valverde, Diana

    2015-04-20

    In pulmonary arterial hypertension (PAH) an association with a polymorphism in the endothelin gene (EDN1) has been described. The main objective of this study was to analyze the polymorphism K198N in the gene EDN1 in patients with PAH, correlating the results with clinical and hemodynamic parameters. We compared 41 patients diagnosed with idiopathic and associated PAH of group i with 50 healthy controls. Polymerase chain reaction and direct sequencing were used to analyze the polymorphism K198N. We compared the genotype distribution and searched for a correlation with clinical, hemodynamic and therapeutic response. Genotype GG was present in 42% of patients in this study and 65% of controls. The GT+TT genotypes appeared in 58% of patients and in 35% of controls. Statistically significant differences between patients and controls (P=.032) were detected, with a relative risk in carriers of having the T allele of 2.51 (95% CI 1.07 to 5.86). The analysis by PolyPhen software defined K198N change as pathogenic. No significant differences in the response to treatment at medium term were found. The genotype analysis of the EDN1 gene polymorphism shows statistically significant differences in patients with PAH compared to healthy individuals. Individuals carrying at least one T allele exhibit a higher relative significant risk to develop HAP. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  13. Lack of association of TNFalpha gene polymorphisms and recurrent pregnancy loss in Caucasian women.

    PubMed

    Pietrowski, Detlef; Bettendorf, Herta; Keck, Christoph; Bürkle, Bernd; Unfried, Gertrud; Riener, Eva-Katrin; Hefler, Lukas A; Tempfer, Clemens

    2004-02-01

    The tumor necrosis factor alpha (TNFalpha) gene plays an important role in immunology and inflammation. Variant alleles of TNFalpha are associated with altered RNA and serum protein levels in humans. Conflicting results have been obtained regarding the role of TNFalpha during pregnancy and recurrent pregnancy loss (RPL). This study investigated the relationship between RPL and two polymorphisms in the promoter of the TNFalpha gene (TNFalpha -308 and -863). Genotyping was performed in 168 RPL women and 212 ethnically matched healthy individuals. In addition, we performed analysis of TNFalpha serum protein levels. We demonstrate that neither the polymorphism -308 nor the polymorphism -863 of the TNFalpha gene is associated with RPL in Caucasian women. In addition, we did not find any association between TNFalpha serum levels and the occurrence of RPL in a subset of 36 RPL women and 36 healthy individuals. We conclude that TNFalpha polymorphisms and resting blood TNFalpha levels do not correlate with the propensity to recurrent pregnancy loss in Caucasian women.

  14. LPA gene: interaction between the apolipoprotein(a) size ('kringle IV' repeat) polymorphism and a pentanucleotide repeat polymorphism influences Lp(a) lipoprotein level.

    PubMed

    Røsby, O; Berg, K

    2000-01-01

    In order to search for factors influencing the Lp(a) lipoprotein level, we have examined the apolipoprotein(a) (apo(a)) size polymorphism as well as a pentanucleotide (TTTTA) repeat polymorphism in the 5' control region of the LPA gene. Lp(a) lipoprotein levels were compared between individuals with different genotypes as defined by pulsed field gel electrophoresis of DNA plugs, and PCR of DNA samples followed by polyacrylamide gel electrophoresis. DNA plugs and DNA were prepared from blood samples collected from blood donors. Twenty-seven different K IV repeat alleles were observed in the 71 women and 92 men from which apo(a) size polymorphism results were obtained. Alleles encoding 26-32 Kringle IV repeats were the most frequent. Alleles encoding seven to 11 TTTTA repeats were detected in the 84 women and 122 men included in the pentanucleotide polymorphism study, and homozygosity for eight TTTTA repeats was the most common genotype. The eight TTTTA repeat allele occurred with almost any apo(a) allele. An inverse relationship between number of K IV repeats and Lp(a) concentration was confirmed. The contributions of the apo(a) size polymorphism and the pentanucleotide repeat polymorphism to the interindividual variance of Lp(a) lipoprotein concentrations were 9.7 and 3.5%, respectively (type IV sum of squares). Nineteen per cent of the variance in Lp(a) lipoprotein level appeared to be the result of the multiplication product (interaction) between the apo(a) size polymorphism and the pentanucleotide repeat polymorphism. The contribution of the apo(a) size polymorphism alone to the variation in Lp(a) lipoprotein level was lower than previously reported. However, the multiplicative interaction effect between the K IV repeat polymorphism and the pentanucleotide repeat polymorphism may be an important factor explaining the variation in Lp(a) lipoprotein levels among the populations.

  15. Single-nucleotide polymorphism-gene intermixed networking reveals co-linkers connected to multiple gene expression phenotypes

    PubMed Central

    Gong, Bin-Sheng; Zhang, Qing-Pu; Zhang, Guang-Mei; Zhang, Shao-Jun; Zhang, Wei; Lv, Hong-Chao; Zhang, Fan; Lv, Sa-Li; Li, Chuan-Xing; Rao, Shao-Qi; Li, Xia

    2007-01-01

    Gene expression profiles and single-nucleotide polymorphism (SNP) profiles are modern data for genetic analysis. It is possible to use the two types of information to analyze the relationships among genes by some genetical genomics approaches. In this study, gene expression profiles were used as expression traits. And relationships among the genes, which were co-linked to a common SNP(s), were identified by integrating the two types of information. Further research on the co-expressions among the co-linked genes was carried out after the gene-SNP relationships were established using the Haseman-Elston sib-pair regression. The results showed that the co-expressions among the co-linked genes were significantly higher if the number of connections between the genes and a SNP(s) was more than six. Then, the genes were interconnected via one or more SNP co-linkers to construct a gene-SNP intermixed network. The genes sharing more SNPs tended to have a stronger correlation. Finally, a gene-gene network was constructed with their intensities of relationships (the number of SNP co-linkers shared) as the weights for the edges. PMID:18466544

  16. 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.

  17. CCR5 chemokine receptor gene polymorphisms in ocular toxoplasmosis.

    PubMed

    de Faria Junior, Geraldo M; Ayo, Christiane M; de Oliveira, Amanda P; Lopes, Alessandro G; Frederico, Fábio B; Silveira-Carvalho, Aparecida P; Previato, Mariana; Barbosa, Amanda P; Murata, Fernando H A; de Almeida Junior, Gildásio Castello; Siqueira, Rubens Camargo; de Mattos, Luiz C; Brandão de Mattos, Cinara C

    2018-02-01

    CC chemokine receptor type 5 (CCR5) is a chemokine receptor that influences the immune response to infectious and parasitic diseases. This study aimed to determine whether the CCR5Δ32 and CCR5 59029 A/G polymorphisms are associated with the development of ocular toxoplasmosis in humans. Patients with positive serology for Toxoplasma gondii were analyzed and grouped as 'with ocular toxoplasmosis' (G1: n=160) or 'without ocular toxoplasmosis' (G2: n=160). A control group (G3) consisted of 160 individuals with negative serology. The characterization of the CCR5Δ32 and CCR5 59029 A/G polymorphisms was by PCR and by PCR-RFLP, respectively. The difference between the groups with respect to the mean age (G1: mean age: 47.3, SD±19.3, median: 46 [range: 18-95]; G2: mean age: 61.3, SD±13.7, median: 61 [range: 21-87]; G3: mean age: 38.8, SD±17.9, median: 34 [range: 18-80]) was statistically significant (G1 vs.G2: p-value <0.0001; t=7.21; DF=318; G1 vs.G3: p-value <0.0001; t=4.32; DF=318; G2 vs. G3: p-value <0.0001; t=9.62; DF=318). The Nagelkerke r 2 value was 0.040. There were statistically significant differences for the CCR5/CCR5 (p-value=0.008; OR=0.261), AA (p-value=0.007; OR=2.974) and AG genotypes (p-value=0.018; OR=2.447) between G1 and G2. Individuals with the CCR5/CCR5 genotype and simultaneously the CCR5-59029 AA or AG genotypes have a greater risk of developing ocular toxoplasmosis (4% greater), which may be associated with a strong and persistent inflammatory response in ocular tissue. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. 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

  19. Polymorphism of the prion protein gene (PRNP) in two Chinese indigenous cattle breeds.

    PubMed

    Qin, L H; Zhao, Y M; Bao, Y H; Bai, W L; Chong, J; Zhang, G L; Zhang, J B; Zhao, Z H

    2011-08-01

    Prion protein (PRNP) gene has been located at position q17 of chromosome 13 in cattle. The polymorphisms of PRNP gene might be associated with BSE susceptibility. In the present work, we investigated the polymorphisms of PRNP gene, including SNP in exon 3, 23-bp indel in promoter region, 12-bp indel in intron 1 in 2 Chinese indigenous cattle breeds of northeast China. Eighty-six animals from Yanbian (34) and Chinese Red Steppes (52) were genotyped at PRNP locus by analyzing genomic DNA. A total of 4 single nucleotide polymorphism (SNP) sites were revealed in the PRNP gene exon 3 of the 2 cattle breeds investigated. Three of these SNPs were non-synonymous mutations that resulted in the amino acid exchanges (K119N, S154N, and M177V), and one is silent nucleotide substitutions (A234G). The two amino acid mutations of S154N and M177V were detected only in Yanbian with a very low frequency (0.0147), and they appears to be absent in Chinese Red Steppes. The average gene heterozygosity (He), effective allele numbers (Ne), Shannon's information index (I) and polymorphism information content (PIC) were 0.3088, 1.5013, 0.3814 and 0.2000 in Yanbian, respectively, being relatively higher than that of Chinese Red Steppes (0.2885, 1.4985, 0.3462 and 0.1873, respectively). In 23-bp indel and 12-bp indel loci, three different genotypes were identified in both Yanbian and Chinese Red Steppes breeds. Based 23- and 12-bp indels, four haplotypes was constructed in the 2 Chinese cattle breeds, of which the 23-bp (-)/12-bp (-) was main haplotypes accounting for more than 50% of the total in both Yanbian and Chinese Red Steppes breeds. These results might be useful in understanding the genetic characteristics of PRNP gene in Chinese indigenous cattle breeds.

  20. 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

  1. Promoter polymorphisms in genes involved in porcine myogenesis influence their transcriptional activity.

    PubMed

    Bongiorni, Silvia; Tilesi, Francesca; Bicorgna, Silvia; Iacoponi, Francesca; Willems, Daniela; Gargani, Maria; D'Andrea, MariaSilvia; Pilla, Fabio; Valentini, Alessio

    2014-11-07

    Success of meat production and selection for improvement of meat quality is among the primary aims in animal production. Meat quality traits are economically important in swine; however, the underlying genetic nature is very complex. Therefore, an improved pork production strongly depends on identifying and studying how genetic variations contribute to modulate gene expression. Promoters are key regions in gene modulation as they harbour several binding motifs to transcription regulatory factors. Therefore, polymorphisms in these regions are likely to deeply affect RNA levels and consequently protein synthesis. In this study, we report the identification of single nucleotide polymorphisms (SNPs) in promoter regions of candidate genes involved in development, cellular differentiation and muscle growth in Sus scrofa. We identified SNPs in the promoter regions of genes belonging to the Myogenic Regulatory Factors (MRF) gene family (the Myogenic Differentiation gene, MYOD1) and to Growth and Differentiation Factors (GDF) gene family (Myostatin gene, MSTN, GDF8), in Casertana and Large White breeds. The purpose of this study was to investigate if polymorphisms in the promoters could affect the transcriptional activity of these genes. With this aim, we evaluated in vitro the functional activity of the luciferase reporter gene luc2 activity, driven by two constructs carrying different promoter haplotypes. We tested the effects of the G302A (U12574) transition on the promoter efficiency in MYOD1 gene. We ascertained a difference in transcription efficiency for the two variants. A stronger activity of the A-carrying construct is more evident in C2C12. The luciferase expression driven by the MYOD1-A allelic variant displayed a 3.8-fold increased transcriptional activity. We investigated the activity of two haplotype variants (AY527152) in the promoter of GDF8 gene. The haploptype-1 (A435-A447-A879) up-regulated the expression of the reporter gene by a two-fold increase, and

  2. G-protein-coupled estrogen receptor-30 gene polymorphisms are associated with uterine leiomyoma risk.

    PubMed

    Kasap, Burcu; Öztürk Turhan, Nilgün; Edgünlü, Tuba; Duran, Müzeyyen; Akbaba, Eren; Öner, Gökalp

    2016-01-06

    The G-protein-coupled estrogen receptor (GPR30, GPER-1) is a member of the G-protein-coupled receptor 1 family and is expressed significantly in uterine leiomyomas. To understand the relationship between GPR30 single nucleotide polymorphisms and the risk of leiomyoma, we measured the follicle-stimulating hormone (FSH) and estradiol (E2) levels of 78 perimenopausal healthy women and 111 perimenopausal women with leiomyomas. The participants' leiomyoma number and volume were recorded. DNA was extracted from whole blood with a GeneJET Genomic DNA Purification Kit. An amplification-refractory mutation system polymerase chain reaction approach was used for genotyping of the GPR30 gene (rs3808350, rs3808351, and rs11544331). The differences in genotype and allele frequencies between the leiomyoma and control groups were calculated using the chi-square (χ2) and Fischer's exact test. The median FSH level was higher in controls (63 vs. 10 IU/L, p=0.000), whereas the median E2 level was higher in the leiomyoma group (84 vs. 9.1 pg/mL, p=0.000). The G allele of rs3808351 and the GG genotype of both the rs3808350 and rs3808351 polymorphisms and the GGC haplotype increased the risk of developing leiomyoma. There was no significant difference in genotype frequencies or leiomyoma volume. However, the GG genotype of the GPR30 rs3808351 polymorphism and G allele of the GPR30 rs3808351 polymorphism were associated with the risk of having a single leiomyoma. Our results suggest that the presence of the GG genotype of the GPR30 rs3808351 polymorphism and the G allele of the GPR30 rs3808351 polymorphism affect the characteristics and development of leiomyomas in the Turkish population.

  3. G-protein-coupled estrogen receptor-30 gene polymorphisms are associated with uterine leiomyoma risk

    PubMed Central

    Kasap, Burcu; Turhan, Nilgün Öztürk; Edgünlü, Tuba; Duran, Müzeyyen; Akbaba, Eren; Öner, Gökalp

    2016-01-01

    The G-protein-coupled estrogen receptor, GPER-1) is a member of the G-protein-coupled receptor 1 family and is expressed significantly in uterine leiomyomas. To understand the relationship between GPR30 single nucleotide polymorphisms and the risk of leiomyoma, we measured the follicle-stimulating hormone (FSH) and estradiol (E2) levels of 78 perimenopausal healthy women and 111 perimenopausal women with leiomyomas. The participants’ leiomyoma number and volume were recorded. DNA was extracted from whole blood with a GeneJET Genomic DNA Purification Kit. An amplification-refractory mutation system polymerase chain reaction approach was used for genotyping of the GPR30 gene (rs3808350, rs3808351, and rs11544331). The differences in genotype and allele frequencies between the leiomyoma and control groups were calculated using the chi-square (χ2) and Fischer’s exact test. The median FSH level was higher in controls (63 vs. 10 IU/L, p=0.000), whereas the median E2 level was higher in the leiomyoma group (84 vs. 9.1 pg/mL, p=0.000). The G allele of rs3808351 and the GG genotype of both the rs3808350 and rs3808351 polymorphisms and the GGC haplotype increased the risk of developing leiomyoma. There was no significant difference in genotype frequencies or leiomyoma volume. However, the GG genotype of the GPR30 rs3808351 polymorphism and G allele of the GPR30 rs3808351 polymorphism were associated with the risk of having a single leiomyoma. Our results suggest that the presence of the GG genotype of the GPR30 rs3808351 polymorphism and the G allele of the GPR30 rs3808351 polymorphism affect the characteristics and development of leiomyomas in the Turkish population. PMID:26773178

  4. Association of Genetic Polymorphisms in TNF and MIF Gene with the Risk of Primary Dysmenorrhea.

    PubMed

    Dogru, Hatice Yilmaz; Ozsoy, Asker Zeki; Karakus, Nevin; Delibas, Ilhan Bahri; Isguder, Cigdem Kunt; Yigit, Serbulent

    2016-08-01

    Primary dysmenorrhea, which affects 90 % of adolescent girls and more than 50 % of menstruating women worldwide, is characterized by recurrent pain during menses in the absence of a detectable organic disease. The aim of this study is to assess the association between MIF -173 and TNF -308 genetic polymorphisms and the clinical features of primary dysmenorrhea. The study population comprised 154 unrelated female patients with clinical diagnosis of dysmenorrhea, and a total of 144 control subjects were recruited consecutively. The MIF -173G > C promoter polymorphism (rs755622) and TNF gene -308G > A (rs1800629) polymorphism were analyzed by polymerase chain reaction-based restriction fragment length polymorphism assay. Two fragments (268 and 97 bp) were seen when the G allele was present at position -173, and three fragments (206, 97, and 62 bp) were observed when the C allele was present. Two fragments (87 and 20 bp) were seen when G allele was present at position -308. There were statistically significant associations between age at menarche and history of back pain among dysmenorrhea patients and MIF gene -173G > C polymorphism (p = 0.003 and p = 0.042, respectively). The genotype and allele frequencies of -308G > A polymorphism showed statistically significant differences between dysmenorrhea patients and controls (p = 0.023 and p = 0.009, respectively). A high association was also observed when the patients were compared with the controls according to the GG genotype versus GA+AA genotypes (p = 0.009). The present study showed that the TNF-α -308 GG genotype may be a useful tool to predict the susceptibility of dysmenorrhea.

  5. Association between thrombophilia gene polymorphisms and recurrent pregnancy loss risk in the Iranian population.

    PubMed

    Bigdeli, Razieh; Younesi, Mohammad Reza; Panahnejad, Erfan; Asgary, Vahid; Heidarzadeh, Samaneh; Mazaheri, Hoda; Aligoudarzi, Samira Louni

    2018-04-15

    Miscarriage is the most common complication in pregnancy. Considering the importance of the problem thrombophilia in pregnant women and its association with recurrent pregnancy loss (RPL), analysis of polymorphisms of genes involved in thrombophilia can be useful. We investigated the frequency and association between ten polymorphisms of seven thrombophilia genes and RPL in an Iranian population. This case-control study was conducted on 200 women with recurrent pregnancy loss and also on 200 women with at least one successful pregnancy as the control group. Using PCR-RFLP, DNA from samples were analyzed for carrying A5279G, A4070G, and FV Leiden of factor V; FXIII (Val34Leu); FII (A20210G); BF (-455 G⁄A); ITGB3 (1565T⁄C); 677C/T and 1298A/C of MTHFR; and PAI-1 (-675 I/D, 5G/4G) polymorphisms. The BF(-455 G⁄A), MTHFR (677 C⁄T, 1298A⁄ C), PAI-1 (-675 I/D,4G⁄ 5G), FV Leiden, FV (A5279G), FXIII (Val34Leu) polymorphisms, which had shown positive relation, and ITGB3 1565T⁄C were the polymorphisms with negative relation to RPL. But in this study it is indicated that there is no significant association between FII (A20210G) and FV (A4070G) polymorphism and RPL. All the data acquired from the RPL patients in this experiment illustrate the importance of screening thrombophilia. Nevertheless, more studies on large-scale populations may be needed to identify novel genetic variants. ASRM: American Society of Reproductive Medicine; HHCY: hyperhomocysteinemia; MTHFR: methylenetetrahydrofolate reductase; PCR: polymerase chain reaction; PAGE: poly-acrylamide gel electrophoresis; RPL: recurrent pregnancy loss.

  6. Polymorphisms in VDR gene in Tunisian postmenopausal women are associated with osteopenia phenotype.

    PubMed

    Sassi, R; Sahli, H; Souissi, C; Sellami, S; Ben Ammar El Gaaied, A

    2015-01-01

    Osteopenia is characterized by intermediate values of bone mineral density (BMD) as compared to normal and osteoporotic subjects. BMD, a surrogate phenotype for osteoporosis, is influenced in part by genetic factors. Among the genes associated with BMD, the vitamin D receptor (VDR) was the first gene studied as a potential candidate associated with BMD in adult and postmenopausal bone loss. However, results are controversial. To determine whether VDR polymorphisms ApaI and TaqI are associated with BMD, osteopenia, osteoporosis and low-impact fracture risk in North Africans, these genotypes were analyzed in 566 postmenopausal Tunisian women. In postmenopausal Tunisian women, the GT ApaI genotype seems to be protective against osteoporosis development (p = 0.02; odds ratio = 0.54). Moreover, the presence of the combined GT/TT genotype of ApaI and TaqI polymorphisms is more frequent in normal BMD women than in osteoporotic women (p = 0.00; odds ratio = 0.41). Interestingly, the GG ApaI genotype is associated with osteopenia development (p = 0.02; odds ratio = 1.86) and also the TT TaqI polymorphism (p = 0.02; odds ratio = 1.53). The GG ApaI genotype is associated with a three times risk of vertebral fracture. The ApaI polymorphism showed an association with osteopenia and low-impact vertebral fracture incidence but not with osteoporosis. The TaqI polymorphism is associated specifically with the osteopenia phenotype. The presence of the two polymorphisms increases the risk to develop osteopenia in postmenopausal Tunisian women. Osteopenia seems to be genetically determined. However, osteoporosis is the result of interaction between genetic and environmental factors.

  7. A Study of the Impact of Death Receptor 4 (DR4) Gene Polymorphisms in Alzheimer's Disease.

    PubMed

    Edgünlü, Tuba Gökdoğan; Ozge, Aynur; Yalın, Osman Özgür; Kul, Seval; Erdal, Mehmet Emin

    2013-09-01

    Excessive apoptosis is believed to play a role in many degenerative and non-degenerative neurological diseases including Alzheimer's disease (AD). Much recent data suggest that apoptotic mechanisms may represent the missing link between Aβ deposition and proteolysis of tau protein. However, there is emerging evidence that apoptotic mechanisms may play a role in Alzheimer's Disease pathogenesis in the absence of overt apoptosis. TNF-related apoptosis inducing ligand receptor 1 (Death Receptor 4, DR4) might impair the apoptotic signal transduction and lead to dysregulation of the homeostasis between cell survival and cell death. The aim of our study was to further investigate the relationship between genetic variants of DR4 and Alzheimer's Disease. Case control study. Sixty-eight patients with AD were included in the study. The control group comprised 72 subjects without signs of neurodegenerative diseases, as evidenced by the examination.DNA was extracted from whole blood using the salting-out procedure. Genotypes were identified by restriction fragment length polymorphism analysis of polymerase chain reaction (PCR-RFLP) products. We observed significant differences in the genotypic distribution of the rs6557634 polymorphism in AD patients compared with controls (p<0.05); our data suggest that the GA genotype in rs6557634 could be protective against AD (p<0.05). However, there were no significant differences between AD patients and control groups in terms of the DR4 rs20575 polymorphism (p>0.05) and the DR4 rs20576 polymorphism (p>0.05). According to haplotype analysis of the DR4 gene for rs6557634, rs20575 and rs20576 polymorphisms, GCA and GCC haplotypes might be a risk factor for AD. Also, we have shown that ACA, GGC and GGA haplotypes might be protective factors against AD. The present results indicate for the first time the possible contribution of the DR4 gene rs6557634, rs20575, rs20576 polymorphisms in Alzheimer's Disease, which may influence susceptibility

  8. Interleukin-10 gene polymorphisms and hepatocellular carcinoma susceptibility: A meta-analysis

    PubMed Central

    Wei, Yong-Gang; Liu, Fei; Li, Bo; Chen, Xi; Ma, Yu; Yan, Lv-Nan; Wen, Tian-Fu; Xu, Ming-Qing; Wang, Wen-Tao; Yang, Jia-Yin

    2011-01-01

    AIM: To assess the association between Interleukin-10 (IL-10) gene IL-10-1082 (G/A), IL-10-592(C/A), IL-10-819 (T/C) polymorphisms and hepatocellular carcinoma (HCC) susceptibility. METHODS: Two investigators independently searched the Medline, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine Database. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for IL-10 polymorphisms and HCC were calculated in a fixed-effects model (the Mantel-Haenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate. RESULTS: This meta-analysis included seven eligible studies, which included 1012 HCC cases and 2308 controls. Overall, IL-10-1082 G/A polymorphism was not associated with the risk of HCC (AA vs AG + GG, OR = 1.11, 95% CI = 0.90-1.37). When stratifying for ethnicity, the results were similar (Asian, OR = 1.12, 95% CI = 0.87-1.44; non-Asian, OR = 1.10, 95% CI = 0.75-1.60). In the overall analysis, the IL-10 polymorphism at position -592 (C/A) was identified as a genetic risk factor for HCC among Asians; patients carrying the IL-10-592*C allele had an increased risk of HCC (OR = 1.29, 95% CI = 1.12-1.49). No association was observed between the IL-10-819 T/C polymorphism and HCC susceptibility (TT vs TC + CC, OR = 1.02, 95% CI = 0.79-1.32). CONCLUSION: This meta-analysis suggests that IL-10-592 A/C polymorphism may be associated with HCC among Asians. IL-10-1082 G/A and IL-10-819 T/C polymorphisms were not detected to be related to the risk for HCC. PMID:22025883

  9. Structure and polymorphism of the mouse prion protein gene.

    PubMed Central

    Westaway, D; Cooper, C; Turner, S; Da Costa, M; Carlson, G A; Prusiner, S B

    1994-01-01

    Missense mutations in the prion protein (PrP) gene, overexpression of the cellular isoform of PrP (PrPC), and infection with prions containing the scrapie isoform of PrP (PrPSc) all cause neurodegenerative disease. To understand better the physiology and expression of PrPC, we retrieved mouse PrP gene (Prn-p) yeast artificial chromosome (YAC), cosmid, phage, and cDNA clones. Physical mapping positions Prn-p approximately 300 kb from ecotropic virus integration site number 4 (Evi-4), compatible with failure to detect recombination between Prn-p and Evi-4 in genetic crosses. The Prn-pa allele encompasses three exons, with exons 1 and 2 encoding the mRNA 5' untranslated region. Exon 2 has no equivalent in the Syrian hamster and human PrP genes. The Prn-pb gene shares this intron/exon structure but harbors an approximately 6-kb deletion within intron 2. While the Prn-pb open reading frame encodes two amino acid substitutions linked to prolonged scrapie incubation periods, a deletion of intron 2 sequences also characterizes inbred strains such as RIII/S and MOLF/Ei with shorter incubation periods, making a relationship between intron 2 size and scrapie pathogenesis unlikely. The promoter regions of a and b Prn-p alleles include consensus Sp1 and AP-1 sites, as well as other conserved motifs which may represent binding sites for as yet unidentified transcription factors. Images PMID:7912827

  10. The BTNL2 G16071A gene polymorphism increases granulomatous disease susceptibility

    PubMed Central

    Tong, Xiang; Ma, Yao; Niu, Xundong; Yan, Zhipeng; Liu, Sitong; Peng, Bo; Peng, Shifeng; Fan, Hong

    2016-01-01

    Abstract Objective: The butyrophilin-like 2 (BTNL2) G16071A gene polymorphism has been implicated in the susceptibility to granulomatous diseases, but the results were inconclusive. The objective of the current study was to precisely explore the relationship between BTNL2 G16071A gene polymorphism and granulomatous disease susceptibility by the meta-analysis including false-positive report probability (FPRP) test. Methods: A systematic literature search in the PubMed, Embase, and Wanfang databases, China National Knowledge Internet, and commercial Internet search engines was conducted to identify studies published up to April 1, 2016. The odds ratio (OR) with 95% confidence interval (CI) was used to assess the effect size. Statistical analysis was conducted using the STATA 12.0 software and FPRP test sheet. Results: In total, all 4324 cases and 4386 controls from 14 eligible studies were included in the current meta-analysis. By the overall meta-analysis, we found a significant association between BTNL2 G16071A gene polymorphism and granulomatous disease susceptibility (A vs G: OR = 1.25, 95% CI = 1.07–1.45, P = 0.005). The meta-regression analyses showed that a large proportion of the between-study heterogeneity was significantly attributed to the ethnicity (A vs G, P = 0.013) and the types of granulomatous diseases (A vs G, P = 0.002). By the subgroup meta-analysis, the BTNL2 G16071A gene polymorphism was associated with granulomatous disease susceptibility in Caucasians (A vs G: OR = 1.37, 95% CI = 1.18–1.58, P < 0.001). Moreover, a significant relationship between the BTNL2 G16071A gene polymorphism and sarcoidosis susceptibility (A vs G: OR = 1.52, 95% CI = 1.39–1.66, P < 0.001) was found. However, to avoid the “false-positive report,” we further investigated the significant associations observed in the present meta-analysis by the FPRP test. Interestingly, the results of FPRP test indicated that the BTNL2

  11. Localization, structure and polymorphism of two paralogous Xenopus laevis mitochondrial malate dehydrogenase genes.

    PubMed

    Tlapakova, Tereza; Krylov, Vladimir; Macha, Jaroslav

    2005-01-01

    Two paralogous mitochondrial malate dehydrogenase 2 (Mdh2) genes of Xenopus laevis have been cloned and sequenced, revealing 95% identity. Fluorescence in-situ hybridization (FISH) combined with tyramide amplification discriminates both genes; Mdh2a was localized into chromosome q3 and Mdh2b into chromosome q8. One kb cDNA probes detect both genes with 85% accuracy. The remaining signals were on the paralogous counterpart. Introns interrupt coding sequences at the same nucleotide as defined for mouse. Restriction polymorphism has been detected in the first intron of Mdh2a, while the individual variability in intron 6 of Mdh2b gene is represented by an insertion of incomplete retrotransposon L1Xl. Rates of nucleotide substitutions indicate that both genes are under similar evolutionary constraints. X. laevis Mdh2 genes can be used as markers for physical mapping and linkage analysis.

  12. C677T (RS1801133 ) MTHFR gene polymorphism frequency in a colombian population

    PubMed Central

    Gómez-Gutierrez, Alberto; Gómez, Piedad Elena; Casas-Gomez, Maria Consuelo; Briceño, Ignacio

    2015-01-01

    Introduction: Abnormal levels of the enzyme methylenetetrahydrofolate reductase (MTHFR) are associated with an increased risk of both cardiovascular and cerebrovascular disease and higher concentrations of homocysteine. Abnormal levels are also related to birth defects, pregnancy complications, cancer and toxicity to methotrexate (MTX). Polymorphisms of MTHFR affect the activity of the enzyme. Genetic associations have been related to treatment efficacy. Objective: To establish the frequency of the C> T polymorphism at nucleotide 677 of the MTHFR gene in a group of Colombian individuals. Methods: Data from pharmacogenetic microarrays that include MTX sensibility-associated polymorphisms were retrospectively collected (Pathway Genomics®). The frequency of the C> T MTHFR rs1801133 marker polymorphism was analyzed. Results: Microarray data from 68 men and 84 women were analyzed. Comparisons of genotype C/C vs. C/T and T/T were statistically significantly different (p= 0.00, p= 0.026, respectively), as were C/T and T / T (p= 0.0001). Conclusions: Results for the C/C and C/T genotypes in a Colombian population are similar to other previously studied groups of healthy subjects. Subjects from our population might be at risk of developing diseases associated with MTHFR polymorphisms and might present toxicity and adverse effects if treated with MTX, which suggests the need to evaluate therapeutic alternatives based on individual pharmacogenetic studies. PMID:26309343

  13. Interferon Regulatory Factor 5 Gene Polymorphisms in Iranian Women with Unexplained Recurrent Pregnancy Loss.

    PubMed

    Amiri Jahromi, Rakhshan; Nasiri, Mahboobeh; Jahromi, Athar Rasekh

    2017-01-01

    This study aimed to examine the association of three functional IRF5 rs10954213, rs3757385, and rs41298401 polymorphisms with susceptibility to unexplained recurrent pregnancy loss (RPL) among Iranian women from south of Iran. 176 women with unexplained RPL and 173 healthy postmenopausal controls were enrolled in this case-control study. Genotyping of the polymorphisms rs10954213 and rs3757385 was carried out using touchdown tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS PCR), and polymorphism rs41298401 was typed using PCR-restriction fragment length polymorphism (PCR-RFLP). Genotype frequencies were significantly different between RPL cases and controls regarding AG heterozygote genotype of rs10954213, GT genotype of rs3757385, and GG genotype of rs41298401. In addition, allele variants (G for rs10954213, T for rs3757385, and G for rs41298401) showed protective role against RPL, while GG haplotype of two first variants was shown to be a susceptibility factor for the disease. These data provide the first evidence, to our knowledge, of the protective role of the studied IRF5 gene polymorphisms against unexplained RPL among Iranian women from south of Iran.

  14. Lack of association between ESR1 gene polymorphisms and premature ovarian failure in Serbian women.

    PubMed

    Li, J; Vujovic, S; Dalgleish, R; Thompson, J; Dragojevic-Dikic, S; Al-Azzawi, F

    2014-06-01

    It has previously been reported that estrogen receptor-alpha (ERα) gene (ESR1: estrogen receptor 1) polymorphisms are associated with premature ovarian failure (POF). The aim of this study was to investigate whether these genetic polymorphisms of ESR1 are associated with POF in Serbian women. A series of 197 POF cases matched with 547 fertile controls was recruited by the Institute for Endocrinology, Diabetes and Metabolic Disorders of Serbia between 2007 and 2010. Genomic DNA was extracted from saliva using Oragene® DNA sample collection kits. Two single-nucleotide polymorphisms (SNPs), PvuII and XbaI, in ESR1 were genotyped by dynamic allele-specific hybridization. Haplotype analyses were performed with the restriction fragment length polymorphism method. SNP and haplotype effects were analyzed by logistic regression models. No significant difference was found in the distribution of ESR1 PvuII and XbaI polymorphisms or haplotypes between the POF and control groups. The two ESR1 SNPs, PvuII and XbaI, are not commonly associated with POF in Serbian women and may not contribute to the genetic basis of the condition.

  15. A Delta-Sarcoglycan Gene Polymorphism as a Risk Factor for Hypertrophic Cardiomyopathy

    PubMed Central

    Garrido-Garduño, Martín H.; Pérez-Martínez, Ramón A.; Ruiz, Victor M.; Herrera-Tepatlán, Esteban; Rodríguez-Cruz, Maricela; Jiménez-Vaca, Ana L.; Minauro-Sanmiguel, Fernando; Salamanca-Gómez, Fabio A.

    2012-01-01

    Background: The C allele of c.−94C>G polymorphism of the delta-sarcoglycan gene was associated as a risk factor for coronary spasm in Japanese patients with hypertrophic cardiomyopathy (HCM). Aim: We evaluated whether the c.−94C>G polymorphism can be a risk factor for HCM in Mexican patients. Methods: The polymorphism was genotyped and the risk was estimated in 35 HCM patients and 145 healthy unrelated individuals. Data of this polymorphism reported in Mexican Amerindian populations were included. Results: The C allele frequency in HCM patients was higher with an odds ratio (OR) of 2.37, and the risk for the CC genotype increased to 5.0. The analysis with Mexican Amerindian populations showed that the C allele frequency was significantly higher in HCM patients with an OR of 2.96 and for CC genotype the risk increased to 7.60. Conclusions: The C allele of the c.−94C>G polymorphism is a risk factor for HCM, which is increased by the Amerindian component and can play an important role in the etiology and progression of disease in Mexican patients. PMID:22524166

  16. Paraoxonase-1 gene Q192R polymorphism and reactive oxygen metabolites.

    PubMed

    Kotani, K; Tsuzaki, K; Sakane, N

    2012-01-01

    Paraoxonase-1 (PON1) is a high-density lipoprotein-associated antioxidant enzyme. The Q192R polymorphism of the PON1 gene can protect against oxidative conditions, but the relationship between Q192R polymorphism and oxidative stress-related markers remains controversial. In this study, the diacron reactive oxygen metabolites (d-ROMs) test was used to investigate the relationship between Q192R polymorphism and oxidative stress-related markers in Japanese subjects. Patients without a history of overt cardiovascular disease who were not receiving antioxidant medication were enrolled in a cross-sectional clinic-based study. An allele-specific polymerase chain reaction method was used to assess the PON1 Q192R polymorphism and compare the level of d-ROMs between genotypes. A total of 103 subjects were analysed. The RR genotype was associated with a significantly lower level of d-ROMs than the RQ and QQ genotypes. After multivariate analysis the relationship between the genotypes and level of d-ROMs remained independently significant. The RR genotype may be protective against oxidative stress in cardiovascular diseasefree Japanese subjects. In addition, the d-ROMs test can be useful for examining the role of the PON1 Q192R polymorphism under oxidative conditions.

  17. C677T (RS1801133 ) MTHFR gene polymorphism frequency in a colombian population.

    PubMed

    Romero-Sánchez, Consuelo; Gómez-Gutierrez, Alberto; Gómez, Piedad Elena; Casas-Gomez, Maria Consuelo; Briceño, Ignacio

    2015-01-01

    Abnormal levels of the enzyme methylenetetrahydrofolate reductase (MTHFR) are associated with an increased risk of both cardiovascular and cerebrovascular disease and higher concentrations of homocysteine. Abnormal levels are also related to birth defects, pregnancy complications, cancer and toxicity to methotrexate (MTX). Polymorphisms of MTHFR affect the activity of the enzyme. Genetic associations have been related to treatment efficacy. To establish the frequency of the C> T polymorphism at nucleotide 677 of the MTHFR gene in a group of Colombian individuals. Data from pharmacogenetic microarrays that include MTX sensibility-associated polymorphisms were retrospectively collected (Pathway Genomics(®)). The frequency of the C> T MTHFR rs1801133 marker polymorphism was analyzed. Microarray data from 68 men and 84 women were analyzed. Comparisons of genotype C/C vs. C/T and T/T were statistically significantly different (p= 0.00, p= 0.026, respectively), as were C/T and T / T (p= 0.0001). Results for the C/C and C/T genotypes in a Colombian population are similar to other previously studied groups of healthy subjects. Subjects from our population might be at risk of developing diseases associated with MTHFR polymorphisms and might present toxicity and adverse effects if treated with MTX, which suggests the need to evaluate therapeutic alternatives based on individual pharmacogenetic studies.

  18. Associations between a polymorphism in the hydroxysteroid (11-beta) dehydrogenase 1 gene, neuroticism and postpartum depression.

    PubMed

    Iliadis, S I; Comasco, E; Hellgren, C; Kollia, N; Sundström Poromaa, I; Skalkidou, A

    2017-01-01

    This study examined the association between a single nucleotide polymorphism in the hydroxysteroid (11-beta) dehydrogenase 1 gene and neuroticism, as well as the possible mediatory role of neuroticism in the association between the polymorphism and postpartum depressive symptoms. 769 women received questionnaires containing the Edinburgh Postnatal Depression Scale (EPDS) at six weeks postpartum and demographic data at pregnancy week 17 and 32 and at six weeks postpartum, as well as the Swedish universities Scales of Personality at pregnancy week 32. Linear regression models showed an association between the GG genotype and depressive symptoms. When neuroticism was introduced in the model, it was associated with EPDS score, whereas the association between the GG genotype and EPDS became borderline significant. A path analysis showed that neuroticism had a mediatory role in the association between the polymorphism and EPDS score. The use of the EPDS, which is a self-reporting instrument. Neuroticism was associated with the polymorphism and had a mediatory role in the association between the polymorphism and postpartum depression. This finding elucidates the genetic background of neuroticism and postpartum depression. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. 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.

  20. A meta-analysis of eNOS and ACE gene polymorphisms and risk of pre-eclampsia in women.

    PubMed

    Shaik, A P; Sultana, A; Bammidi, V K; Sampathirao, K; Jamil, K

    2011-10-01

    A meta-analyses of endothelial nitric oxide synthase (eNOS) and angiotensin-converting enzyme (ACE) gene polymorphisms in pre-eclampsia was performed. We shortlisted 33 studies (17 for ACE; 16 for eNOS gene polymorphisms), of which 29 articles (16 for ACE and 15 for eNOS) were analysed. Overall, 1,620 cases with pre-eclampsia and 2,158 controls were analysed for intron 16 insertion-deletion polymorphism in ACE gene. A total of 1,610 subjects with pre-eclampsia and 2,875 controls were analysed for the Glu298Asp in eNOS gene. Overall, the random-effects odds ratio (OR) with Glu298Asp in eNOS gene was 0.958 (95% confidence intervals, CI 0.747-1.228, p > 0.05), and for the insertion-deletion/ACE polymorphism was 0.987 (95% CI 0.698-1.395, p > 0.05). Significant heterogeneity was observed in the studies that evaluated polymorphisms in ACE (Q value = 55.6; I(2) = 73; p value = 0.000); and eNOS (Q value = 37.2; I(2) = 62.4; p value = 0.001) polymorphisms. No significant risk of pre-eclampsia was observed in both eNOS and ACE genes with these polymorphisms.

  1. Polymorphisms in the ghrelin gene and their associations with milk yield and quality in water buffaloes.

    PubMed

    Gil, F M M; de Camargo, G M F; Pablos de Souza, F R; Cardoso, D F; Fonseca, P D S; Zetouni, L; Braz, C U; Aspilcueta-Borquis, R R; Tonhati, H

    2013-05-01

    Ghrelin is a gastrointestinal hormone that acts in releasing growth hormone and influences the body general metabolism. It has been proposed as a candidate gene for traits such as growth, carcass quality, and milk production of livestock because it influences feed intake. In this context, the aim of this study was to verify the existence of polymorphisms in the ghrelin gene and their associations with milk, fat and protein yield, and percentage in water buffaloes (Bubalus bubalis). A group of 240 animals was studied. Five primer pairs were used and 11 single nucleotide polymorphisms (SNP) were found in the ghrelin gene by sequencing. The animals were genotyped for 8 SNP by PCR-RFLP. The SNP g.960G>A and g.778C>T were associated with fat yield and the SNP g.905T>C was associated with fat yield and percentage and protein percentage. These SNP are located in intronic regions of DNA and may be in noncoding RNA sites or affect transcriptional efciency. The ghrelin gene in buffaloes influences milk fat and protein synthesis. The polymorphisms observed can be used as molecular markers to assist selection. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  2. Interleukin-8 gene polymorphism -251T>A contributes to Alzheimer's disease susceptibility.

    PubMed

    Qin, Biyong; Li, Li; Wang, Shanshan; Wu, Jun; Huang, Yulan; Zhou, Ping; Bai, Jiao; Zheng, Yan

    2016-09-01

    Published association studies have investigated the correlation between interleukin-8 (IL-8) gene polymorphism -251T>A and susceptibility to Alzheimer's disease (AD); however, the results are conflicting. Thus, we conducted the meta-analysis to reassess the effect of IL-8 gene -251T>A variant on the risk of AD. Relevant studies regarding this association were electronically searched and identified from the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and the Chinese Biomedicine Database. The odds ratios (ORs) with the corresponding 95% confidence intervals (95% CIs) were pooled to calculate the strength of this association. Nine studies with a total of 1406 cases and 2152 controls were included in the meta-analysis. Overall, a significant association of IL-8 gene -251T>A polymorphism with increased risk of AD was observed in several genetic models (allele, A vs T: OR=1.32, 95%CI=1.16-1.50; homozygous, AA vs TT: OR=1.70, 95%CI=1.21-2.21; heterozygous, TA vs TT: OR=1.37, 95%CI=1.12-1.69; recessive, AA vs TA+TT: OR=1.40, 95%CI=1.12-1.75). Similarly, such association was also revealed both in Asian and European populations in the subgroup analysis by ethnicity. The current study suggested that IL-8 gene polymorphism -251T>A may contribute to the susceptibility to AD.

  3. Polymorphisms in miRNA genes and their involvement in autoimmune diseases susceptibility.

    PubMed

    Latini, Andrea; Ciccacci, Cinzia; Novelli, Giuseppe; Borgiani, Paola

    2017-08-01

    MicroRNAs (miRNAs) are small non-coding RNA molecules that negatively regulate the expression of multiple protein-encoding genes at the post-transcriptional level. MicroRNAs are involved in different pathways, such as cellular proliferation and differentiation, signal transduction and inflammation, and play crucial roles in the development of several diseases, such as cancer, diabetes, and cardiovascular diseases. They have recently been recognized to play a role also in the pathogenesis of autoimmune diseases. Although the majority of studies are focused on miRNA expression profiles investigation, a growing number of studies have been investigating the role of polymorphisms in miRNA genes in the autoimmune diseases development. Indeed, polymorphisms affecting the miRNA genes can modify the set of targets they regulate or the maturation efficiency. This review is aimed to give an overview about the available studies that have investigated the association of miRNA gene polymorphisms with the susceptibility to various autoimmune diseases and to their clinical phenotypes.

  4. Associations between polymorphisms in the antiviral TRIM genes and measles vaccine immunity.

    PubMed

    Ovsyannikova, Inna G; Haralambieva, Iana H; Vierkant, Robert A; O'Byrne, Megan M; Poland, Gregory A

    2013-06-01

    The role of polymorphisms within the antiviral tripartite motif (TRIM) genes in measles vaccine adaptive immune responses was examined. A limited association was found between TRIM5 (rs7122620) and TRIM25 (rs205499) gene polymorphisms and measles-specific antibody levels. However, many associations were found between TRIM gene SNPs and variations in cellular responses (IFN-γ Elispot and secreted cytokines IL-2, IL-6, IL-10, IFN-γ, and TNF-α). TRIM22 rs2291841 was significantly associated with an increased IFN-γ Elispot response (35 vs. 102 SFC per 2×10(5)PBMC, p=0.009, q=0.71) in Caucasians. A non-synonymous TRIM25 rs205498 (in LD with other SNPs, r(2)≥0.56), as well as the TRIM25 AAAGGAAAGGAGT haplotype, was associated with a decreased IFN-γ Elispot response (t-statistic -2.32, p=0.02) in African-Americans. We also identified polymorphisms in the TRIM5, TRIM22, and TRIM25 genes that were associated with significant differences in cytokine responses. Additional studies are necessary to replicate our findings and to examine the functional consequences of these associations. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  5. 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

  6. [Influence of interleukin-1 beta gene polymorphism and childhood maltreatment on antidepressant treatment].

    PubMed

    Chen, Ying; Zhang, Zhijun; Xu, Zhi; Pu, Mengjia; Geng, Leiyu

    2015-12-01

    To explore the influence of interleukin-1 beta (IL1B) gene polymorphism and childhood maltreatment on antidepressant treatment. Two hundred and four patients with major depressive disorder (MDD) have received treatment with single antidepressant drugs and were followed up for 8 weeks. Hamilton depression scale-17 (HAMD-17) was used to evaluate the severity of depressive symptoms and therapeutic effect. Childhood maltreatment was assessed using Childhood Trauma Questionnaire, a 28-item Short Form (CTQ-SF). Single nucleotide polymorphism (SNP) of the IL1B gene was determined using a SNaPshot method. Correlation of rs16944 gene polymorphism with response to treatment was analyzed using Unphased 3.0.13 software. The main and interactive effects of SNP and childhood maltreatment on the antidepressant treatment were analyzed using Logistic regression analysis. No significant difference of gender, age, year of education, family history, episode time, and antidepressant agents was detected between the remitters and non-remitters. Association analysis has found that the SNP rs16944 in the IL1B AA genotype carriers antidepressant response was poorer (χ2=3.931, P=0.047). No significant difference was detected in the CTQ scores between the two groups. Genetic and environmental interaction analysis has demonstrated a significant correlation between rs16944 AA genotype and childhood maltreatment and poorer response to antidepressant treatment. The SNP rs16944 in the IL1B gene and its interaction with childhood maltreatment may influence the effect of antidepressant treatment for patients with MDD.

  7. Polymorphism and genetic mapping of the human oxytocin receptor gene on chromosome 3

    SciTech Connect

    Michelini, S.; Urbanek, M.; Goldman, D.

    1995-06-19

    Centrally administered oxytocin has been reported to facilitate affiliative and social behaviors, in functional harmony with its well-known peripheral effects on uterine contraction and milk ejection. The biological effects of oxytocin could be perturbed by mutations occurring in the sequence of the oxytocin receptor gene, and it would be of interest to establish the position of this gene on the human linkage map. Therefore we identified a polymorphism at the human oxytocin receptor gene. A portion of the 3{prime} untranslated region containing a 30 bp CA repeat was amplified by polymerase chain reaction (PCR), revealing a polymorphism with two allelesmore » occurring with frequencies of 0.77 and 0.23 in a sample of Caucasian CEPH parents (n = 70). The CA repeat polymorphism we detected was used to map the human oxytocin receptor to chromosome 3p25-3p26, in a region which contains several important genes, including loci for Von Hippel-Lindau disease (VHL) and renal cell carcinoma. 53 refs., 2 figs., 1 tab.« less

  8. Oxytocin receptor gene polymorphisms are associated with human directed social behavior in dogs (Canis familiaris).

    PubMed

    Kis, Anna; Bence, Melinda; Lakatos, Gabriella; Pergel, Enikő; Turcsán, Borbála; Pluijmakers, Jolanda; Vas, Judit; Elek, Zsuzsanna; Brúder, Ildikó; Földi, Levente; Sasvári-Székely, Mária; Miklósi, Adám; Rónai, Zsolt; Kubinyi, Enikő

    2014-01-01

    The oxytocin system has a crucial role in human sociality; several results prove that polymorphisms of the oxytocin receptor gene are related to complex social behaviors in humans. Dogs' parallel evolution with humans and their adaptation to the human environment has made them a useful species to model human social interactions. Previous research indicates that dogs are eligible models for behavioral genetic research, as well. Based on these previous findings, our research investigated associations between human directed social behaviors and two newly described (-212AG, 19131AG) and one known (rs8679684) single nucleotide polymorphisms (SNPs) in the regulatory regions (5' and 3' UTR) of the oxytocin receptor gene in German Shepherd (N = 104) and Border Collie (N = 103) dogs. Dogs' behavior traits have been estimated in a newly developed test series consisting of five episodes: Greeting by a stranger, Separation from the owner, Problem solving, Threatening approach, Hiding of the owner. Buccal samples were collected and DNA was isolated using standard protocols. SNPs in the 3' and 5' UTR regions were analyzed by polymerase chain reaction based techniques followed by subsequent electrophoresis analysis. The gene-behavior association analysis suggests that oxytocin receptor gene polymorphisms have an impact in both breeds on (i) proximity seeking towards an unfamiliar person, as well as their owner, and on (ii) how friendly dogs behave towards strangers, although the mediating molecular regulatory mechanisms are yet unknown. Based on these results, we conclude that similarly to humans, the social behavior of dogs towards humans is influenced by the oxytocin system.

  9. DNA repair gene polymorphisms and risk of cutaneous melanoma: a systematic review and meta-analysis.

    PubMed

    Mocellin, Simone; Verdi, Daunia; Nitti, Donato

    2009-10-01

    Polymorphisms of DNA repair-related genes might modulate cancer predisposition. We performed a systematic review and meta-analysis of the available evidence regarding the relationship between these polymorphisms and the risk of developing cutaneous melanoma. Relevant studies were searched using PubMed, Medline, Embase, Cancerlit, Cochrane and ISI Web of Knowledge databases. Data were gathered according to the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. The model-free approach was adopted to perform the meta-analysis of the retrieved data. We identified 20 original reports that describe the relationship between melanoma risk and the single-nucleotide polymorphisms (SNPs) of 16 genes (cases = 4195). For seven SNPs considered in at least two studies, the findings were heterogeneous. Data were suitable for meta-analysis only in the case of the XPD/ERCC2 SNP rs13181 (cases = 2308, controls = 3698) and demonstrated that the variant C allele is associated with increased melanoma risk (odds ratio = 1.12, 95% confidence interval = 1.03-1.21, P = 0.01; population attributable risk = 9.6%). This is the first meta-analysis suggesting that XPD/ERCC2 might represent a low-penetrance melanoma susceptibility gene. Much work is still to be done before definitive conclusions can be drawn on the role of DNA repair alterations in melanomagenesis since for the other genes involved in this highly complex process, the available information is scarce or null.

  10. Oxytocin and Vasopressin Receptor Gene Polymorphisms: Role in Social and Psychiatric Traits

    PubMed Central

    Aspé-Sánchez, Mauricio; Moreno, Macarena; Rivera, Maria Ignacia; Rossi, Alejandra; Ewer, John

    2016-01-01

    Oxytocin (OXT) and arginine-vasopressin (AVP) are two phylogenetically conserved neuropeptides that have been implicated in a wide range of social behaviors. Although a large body of research, ranging from rodents to humans, has reported on the effects of OXT and AVP administration on affiliative and trust behaviors, and has highlighted the genetic contributions of OXT and AVP receptor polymorphisms to both social behaviors and to diseases related to social deficits, the consequences of peptide administration on psychiatric symptoms, and the impact of receptor polymorphisms on receptor function, are still unclear. Despite the exciting advances that these reports have brought to social neuroscience, they remain preliminary and suffer from the problems that are inherent to monogenetic linkage and association studies. As an alternative, some studies are using polygenic approaches, and consider the contributions of other genes and pathways, including those involving DA, 5-HT, and reelin, in addition to OXT and AVP; a handful of report are also using genome-wide association studies. This review summarizes findings on the associations between OXT and AVP receptor polymorphism, social behavior, and psychiatric diseases. In addition, we discuss reports on the interactions of OXT and AVP receptor genes and genes involved in other pathways (such as those of dopamine, serotonin, and reelin), as well as research that has shed some light on the impact of gene polymorphisms on the volume, connectivity, and activation of specific neural structures, differential receptor expression, and plasma levels of the OXT and AVP peptides. We hope that this effort will be helpful for understanding the studies performed so far, and for encouraging the inclusion of other candidate genes not explored to date. PMID:26858594

  11. The effects of polymorphisms in 7 candidate genes on resistance to Salmonella Enteritidis in native chickens.

    PubMed

    Tohidi, R; Idris, I B; Malar Panandam, J; Hair Bejo, M

    2013-04-01

    Salmonella enterica serovar Enteritidis infection is a common concern in poultry production for its negative effects on growth as well as food safety for humans. Identification of molecular markers that are linked to resistance to Salmonella Enteritidis may lead to appropriate solutions to control Salmonella infection in chickens. This study investigated the association of candidate genes with resistance to Salmonella Enteritidis in young chickens. Two native breeds of Malaysian chickens, namely, Village Chickens and Red Junglefowl, were evaluated for bacterial colonization after Salmonella Enteritidis inoculation. Seven candidate genes were selected on the basis of their physiological role in immune response, as determined by prior studies in other genetic lines: natural resistance-associated protein 1 (NRAMP1), transforming growth factor β3 (TGFβ3), transforming growth factor β4 (TGFβ4), inhibitor of apoptosis protein 1 (IAP1), caspase 1 (CASP1), lipopolysaccharide-induced tumor necrosis factor (TNF) α factor (LITAF), and TNF-related apoptosis-inducing ligand (TRAIL). Polymerase chain reaction-RFLP was used to identify polymorphisms in the candidate genes; all genes exhibited polymorphisms in at least one breed. The NRAMP1-SacI polymorphism correlated with the differences in Salmonella Enteritidis load in the cecum (P = 0.002) and spleen (P = 0.01) of Village Chickens. Polymorphisms in the restriction sites of TGFβ3-BsrI, TGFβ4-MboII, and TRAIL-StyI were associated with Salmonella Enteritidis burden in the cecum, spleen, and liver of Village Chickens and Red Junglefowl (P < 0.05). These results indicate that the NRAMP1, TGFβ3, TGFβ4, and TRAIL genes are potential candidates for use in selection programs for increasing genetic resistance against Salmonella Enteritidis in native Malaysian chickens.

  12. Oxytocin and Vasopressin Receptor Gene Polymorphisms: Role in Social and Psychiatric Traits.

    PubMed

    Aspé-Sánchez, Mauricio; Moreno, Macarena; Rivera, Maria Ignacia; Rossi, Alejandra; Ewer, John

    2015-01-01

    Oxytocin (OXT) and arginine-vasopressin (AVP) are two phylogenetically conserved neuropeptides that have been implicated in a wide range of social behaviors. Although a large body of research, ranging from rodents to humans, has reported on the effects of OXT and AVP administration on affiliative and trust behaviors, and has highlighted the genetic contributions of OXT and AVP receptor polymorphisms to both social behaviors and to diseases related to social deficits, the consequences of peptide administration on psychiatric symptoms, and the impact of receptor polymorphisms on receptor function, are still unclear. Despite the exciting advances that these reports have brought to social neuroscience, they remain preliminary and suffer from the problems that are inherent to monogenetic linkage and association studies. As an alternative, some studies are using polygenic approaches, and consider the contributions of other genes and pathways, including those involving DA, 5-HT, and reelin, in addition to OXT and AVP; a handful of report are also using genome-wide association studies. This review summarizes findings on the associations between OXT and AVP receptor polymorphism, social behavior, and psychiatric diseases. In addition, we discuss reports on the interactions of OXT and AVP receptor genes and genes involved in other pathways (such as those of dopamine, serotonin, and reelin), as well as research that has shed some light on the impact of gene polymorphisms on the volume, connectivity, and activation of specific neural structures, differential receptor expression, and plasma levels of the OXT and AVP peptides. We hope that this effort will be helpful for understanding the studies performed so far, and for encouraging the inclusion of other candidate genes not explored to date.

  13. NOS3 gene polymorphisms and exercise hemodynamics in postmenopausal women.

    PubMed

    Hand, B D; McCole, S D; Brown, M D; Park, J J; Ferrell, R E; Huberty, A; Douglass, L W; Hagberg, J M

    2006-12-01

    We tested whether the G894T and T-786C NOS3 polymorphisms were associated with exercise cardiovascular (CV) hemodynamics in sedentary, physically active, and endurance-trained postmenopausal women. CV hemodynamic parameters including heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressures and cardiac output (Q), as determined by acetylene rebreathing, stroke volume (SV), arteriovenous oxygen difference (a-vO2 diff), and total peripheral resistance (TPR) were measured during submaximal (40, 60, 80 %) and maximal (approximately 100 % VO2max) exercise. NOS3 G894T genotype was not significantly associated, either independently or interactively with habitual physical activity (PA) level, with SBP, Q, TPR, or a-vO2 diff during submaximal or maximal exercise. However, NOS3 894T non-carriers had a higher submaximal exercise HR than NOS3 894T allele carriers (120 +/- 2 vs. 112 +/- 2 beats/min, p = 0.007). NOS3 894T allele carriers had a higher SV than 894T non-carriers (78 +/- 2 vs. 72 +/- 2 ml/beat, p = 0.03) during submaximal exercise. NOS3 894T non-carriers also had a higher maximal exercise HR averaged across habitual PA groups than T allele carrier women (165 +/- 2 vs. 158 +/- 2 beats/min, p = 0.04). NOS3 894T allele carriers also tended to have a higher SV during maximal exercise than 894T non-carriers (70 +/- 2 vs. 64 +/- 2 ml/beat, p = 0.08). NOS3 T-786C genotype was not significantly associated, either independently or interactively, with any of the CV hemodynamic measures during submaximal or maximal exercise. These results suggest an association of NOS3 G894T genotype with submaximal and maximal exercise CV hemodynamic responses, especially HR, in postmenopausal women.

  14. Evidence for polymorphism in the cytochrome P450 2D50 gene in horses.

    PubMed

    Corado, C R; McKemie, D S; Young, A; Knych, H K

    2016-06-01

    Metabolism is an essential factor in the clearance of many drugs and as such plays a major role in the establishment of dosage regimens and withdrawal times. CYP2D6, the human orthologue to equine CYP2D50, is a drug-metabolizing enzyme that is highly polymorphic in humans leading to widely differing levels of metabolic activity. As CYP2D6 is highly polymorphic, in this study it was hypothesized that the gene coding for the equine orthologue, CYP2D50, may also be prone to polymorphism. Blood samples were collected from 150 horses, the CYP2D50 gene was cloned and sequenced; and full-length sequences were analyzed for single nucleotide polymorphisms (SNPs), deletions, or insertions. Pharmacokinetic data were collected from a subset of horses following the administration of a single oral dose of tramadol and probit analysis used to calculate metabolic ratios. Prior to drug administration, the ability of recombinant CYP2D50 to metabolize tramadol to O-desmethyltramadol was confirmed. Sequencing of CYP2D50 identified 126 exonic SNPs, with 31 of those appearing in multiple horses. Oral administration of tramadol to a subset of these horses revealed variable metabolic ratios (tramadol: O-desmethyltramadol) in individual horses and separation into three metabolic groups. While a limited number of horses of primarily a single breed were studied, the variability in tramadol metabolism to O-desmethyltramadol between horses and preliminary evidence of what appears to be poor, extensive, and ultra-rapid metabolizers supports further study of the potential for genetic polymorphisms in the CYP2D50 gene in horses. © 2015 John Wiley & Sons Ltd.

  15. Heat shock protein 70 gene polymorphisms are associated with paranoid schizophrenia in the Polish population.

    PubMed

    Kowalczyk, Malgorzata; Owczarek, Aleksander; Suchanek, Renata; Paul-Samojedny, Monika; Fila-Danilow, Anna; Borkowska, Paulina; Kucia, Krzysztof; Kowalski, Jan

    2014-03-01

    HSP70 genes have been considered as promising schizophrenia candidate genes based on their protective role in the central nervous system under stress conditions. In this study, we analyzed the potential implication of HSPA1A +190G/C, HSPA1B +1267A/G, and HSPA1L +2437T/C polymorphisms in the susceptibility to paranoid schizophrenia in a homogenous Caucasian Polish population. In addition, we investigated the association of the polymorphisms with the clinical variables of the disease. Two hundred and three patients with paranoid schizophrenia and 243 healthy controls were enrolled in the study. Polymorphisms of HSPA1A, -1B, and -1L genes were genotyped using the PCR-RFLP technique. Analyses were conducted in entire groups and in subgroups that were stratified according to gender. There were significant differences in the genotype and allele frequencies of HSPA1A polymorphism between the patients and controls. The +190CC genotype and +190C allele were over-represented in the patients and significantly increased the risk for developing schizophrenia (OR = 3.45 and OR = 1.61, respectively). Interestingly, such a risk was higher for females with the +190CC genotype than for males with the +190CC genotype (OR = 5.78 vs. OR = 2.76). We also identified the CGT haplotype as a risk haplotype for schizophrenia and demonstrated the effects of HSPA1A and HSPA1B genotypes on the psychopathology and age of onset. Our study provided the first evidence that the HSPA1A polymorphism may potentially increase the risk of developing paranoid schizophrenia. Further independent analyses in different populations to evaluate the role of gender are needed to replicate these results.

  16. CCR5 gene polymorphism is a genetic risk factor for radiographic severity of rheumatoid arthritis.

    PubMed

    Han, S W; Sa, K H; Kim, S I; Lee, S I; Park, Y W; Lee, S S; Yoo, W H; Soe, J S; Nam, E J; Lee, J; Park, J Y; Kang, Y M

    2012-11-01

    The chemokine receptor [C-C chemokine receptor 5 (CCR5)] is expressed on diverse immune effecter cells and has been implicated in the pathogenesis of rheumatoid arthritis (RA). This study sought to determine whether single-nucleotide polymorphisms (SNPs) in the CCR5 gene and their haplotypes were associated with susceptibility to and severity of RA. Three hundred fifty-seven patients with RA and 383 healthy unrelated controls were recruited. Using a pyrosequencing assay, we examined four polymorphisms -1118 CTAT(ins) (/del) (rs10577983), 303 A>G (rs1799987), 927 C>T (rs1800024), and 4838 G>T (rs1800874) of the CCR5 gene, which were distributed over the promoter region as well as the 5' and 3' untranslated regions. No significant difference in the genotype, allele, and haplotype frequencies of the four selected SNPs was observed between RA patients and controls. CCR5 polymorphisms of -1118 CTAT(del) (P = 0.012; corrected P = 0.048) and 303 A>G (P = 0.012; corrected P = 0.048) showed a significant association with radiographic severity in a recessive model, and, as a result of multivariate logistic regression analysis, were found to be an independent predictor of radiographic severity. When we separated the erosion score from the total Sharp score, the statistical significance of CCR5 polymorphisms showed an increase; -1118 CTAT(ins) (/del) (P = 0.007; corrected P = 0.028) and 303 A>G (P = 0.007; corrected P = 0.028). Neither SNPs nor haplotypes of the CCR5 gene showed a significant association with joint space narrowing score. These results indicate that genetic polymorphisms of CCR5 are an independent risk factor for radiographic severity denoted by modified Sharp score, particularly joint erosion in RA. © 2012 John Wiley & Sons A/S.

  17. Functional polymorphisms in cell death pathway genes FAS and FASL contribute to risk of lung cancer.

    PubMed

    Zhang, X; Miao, X; Sun, T; Tan, W; Qu, S; Xiong, P; Zhou, Y; Lin, D

    2005-06-01

    The FAS and FASL system plays a key role in regulating apoptotic cell death and corruption of this signalling pathway has been shown to participate in immune escape and tumorigenesis. There is reduced expression of FAS but elevated expression of FASL in many types of human cancers including lung cancer. We recently reported an association between functional polymorphisms in FAS (-1377G-->A) and FASL (-844T-->C) and risk of oesophageal cancer. To examine the contribution of these polymorphisms to risk of developing lung cancer. Genotypes of 1000 lung cancer patients and 1270 controls were analysed by PCR based restriction fragment length polymorphism. Associations with risk of lung cancer were estimated by logistic regression. Compared with non-carriers, there was a 1.6 fold excess risk of developing lung cancer for carriers of the FAS -1377AA genotype (odds ratio (OR) 1.59, 95% confidence interval (CI) 1.21 to 2.10; p = 0.001), and 1.8 fold excess risk (OR 1.79, 95% CI 1.26 to 2.52; p = 0.001) for carriers of FASL -844CC. Gene-gene interaction of FAS and FASL polymorphisms increased risk of lung cancer in a multiplicative manner (OR for the carriers of both FAS -1377AA and FASL -844CC genotypes 4.18, 95% CI 2.83 to 6.18). Gene-environment interaction of FAS or FASL polymorphism and smoking associated with increased risk of lung cancer was also found. These results are consistent with our initial findings in oesophageal cancer and further support the hypothesis that the FAS and FASL triggered apoptosis pathway plays an important role in human carcinogenesis.

  18. The association between sex-related interleukin-6 gene polymorphisms and the risk for cerebral palsy.

    PubMed

    Bi, Dan; Chen, Mingjie; Zhang, Xiaoli; Wang, Honglian; Xia, Lei; Shang, Qing; Li, Tongchuan; Zhu, Dengna; Blomgren, Klas; He, Lin; Wang, Xiaoyang; Xing, Qinghe; Zhu, Changlian

    2014-06-06

    The relationship between genetic factors and the development of cerebral palsy (CP) has recently attracted much attention. Polymorphisms in the genes encoding proinflammatory cytokines have been shown to be associated with susceptibility to perinatal brain injury and development of CP. Interleukin-6 (IL-6) is a proinflammatory cytokine that plays a pivotal role in neonatal brain injury, but conflicting results have been reported regarding the association between IL-6 single nucleotide polymorphisms (SNPs) and CP. The purpose of this study was to analyze IL-6 gene polymorphisms and protein expression and to explore the role of IL-6 in the Chinese CP population. A total of 753 healthy controls and 713 CP patients were studied to detect the presence of five SNPs (rs1800796, rs2069837, rs2066992, rs2069840, and rs10242595) in the IL-6 locus. Of these, 77 healthy controls and 87 CP patients were selected for measurement of plasma IL-6 by Luminex assay. The SHEsis program was used to analyze the genotyping data. For all comparisons; multiple testing on each individual SNP was corrected by the SNPSpD program. There were no differences in allele or genotype frequencies between the overall CP patients and controls among the five genetic polymorphisms. However, subgroup analysis found significant sex-related differences in allele and genotype frequencies. Differences were found between spastic CP and controls in males for rs2069837; between CP with periventricular leukomalacia and controls in males for rs1800796 and rs2066992; and between term CP and controls in males for rs2069837. Plasma IL-6 levels were higher in CP patients than in the controls, and this difference was more robust in full-term male spastic CP patients. Furthermore, the genotype has an effect on IL-6 synthesis. The influence of IL-6 gene polymorphisms on IL-6 synthesis and the susceptibility to CP is related to sex and gestational age.

  19. The association between sex-related interleukin-6 gene polymorphisms and the risk for cerebral palsy

    PubMed Central

    2014-01-01

    Background The relationship between genetic factors and the development of cerebral palsy (CP) has recently attracted much attention. Polymorphisms in the genes encoding proinflammatory cytokines have been shown to be associated with susceptibility to perinatal brain injury and development of CP. Interleukin-6 (IL-6) is a proinflammatory cytokine that plays a pivotal role in neonatal brain injury, but conflicting results have been reported regarding the association between IL-6 single nucleotide polymorphisms (SNPs) and CP. The purpose of this study was to analyze IL-6 gene polymorphisms and protein expression and to explore the role of IL-6 in the Chinese CP population. Methods A total of 753 healthy controls and 713 CP patients were studied to detect the presence of five SNPs (rs1800796, rs2069837, rs2066992, rs2069840, and rs10242595) in the IL-6 locus. Of these, 77 healthy controls and 87 CP patients were selected for measurement of plasma IL-6 by Luminex assay. The SHEsis program was used to analyze the genotyping data. For all comparisons; multiple testing on each individual SNP was corrected by the SNPSpD program. Results There were no differences in allele or genotype frequencies between the overall CP patients and controls among the five genetic polymorphisms. However, subgroup analysis found significant sex-related differences in allele and genotype frequencies. Differences were found between spastic CP and controls in males for rs2069837; between CP with periventricular leukomalacia and controls in males for rs1800796 and rs2066992; and between term CP and controls in males for rs2069837. Plasma IL-6 levels were higher in CP patients than in the controls, and this difference was more robust in full-term male spastic CP patients. Furthermore, the genotype has an effect on IL-6 synthesis. Conclusions The influence of IL-6 gene polymorphisms on IL-6 synthesis and the susceptibility to CP is related to sex and gestational age. PMID:24903966

  20. Molecular cloning, polymorphisms, and expression analysis of the RERG gene in indigenous Chinese goats.

    PubMed

    Sui, M X; Wang, H H; Wang, Z W

    2015-11-24

    The current study aimed to investigate the coding sequence, polymorphisms, and expression of the RERG gene in indigenous Chinese goats. cDNA of RERG, obtained through reverse transcription PCR was analyzed using bioinformatic techniques. Polymorphisms in the exon regions of the RERG gene were identified and their associations with growth traits in three varieties of indigenous Chinese goats were investigated. Expression of the RERG gene in three goat breeds of the same age was detected using real-time quantitative PCR. The results revealed that the cDNA of RERG, which contained a complete open reading frame of 20-620 bp, was 629 bp in length. The associated accession numbers in GenBank are JN672576, JQ917222, and JN580309 for the QianBei Ma goat, the GuiZhou white goat, and the GuiZhou black goat, respectively. Four consistent SNP sites were found in the exon regions of the RERG gene for the three goat breeds. mRNA expression of the RERG gene differed between different tissues in adult goats of same age. The highest expression was observed in lung and spleen tissues, while the lowest expression was recorded in thymus gland tissue. In addition, the expression of the RERG gene in the muscle of Guizhou white goat, GuiZhou black goat, and QianBei Ma goat decreased sequentially. Our results lay the foundations for further investigation into the role of the RERG gene in goat growth traits.

  1. Polymorphisms in the AOX2 gene are associated with the rooting ability of olive cuttings.

    PubMed

    Hedayati, Vahideh; Mousavi, Amir; Razavi, Khadijeh; Cultrera, Nicolò; Alagna, Fiammetta; Mariotti, Roberto; Hosseini-Mazinani, Mehdi; Baldoni, Luciana

    2015-07-01

    Different rooting ability candidate genes were tested on an olive cross progeny. Our results demonstrated that only the AOX2 gene was strongly induced. OeAOX2 was fully characterised and correlated to phenotypical traits. The formation of adventitious roots is a key step in the vegetative propagation of trees crop species, and this ability is under strict genetic control. While numerous studies have been carried out to identify genes controlling adventitious root formation, only a few loci have been characterised. In this work, candidate genes that were putatively involved in rooting ability were identified in olive (Olea europaea L.) by similarity with orthologs identified in other plant species. The mRNA levels of these genes were analysed by real-time PCR during root induction in high- (HR) and low-rooting (LR) individuals. Interestingly, alternative oxidase 2 (AOX2), which was previously reported to be a functional marker for rooting in olive cuttings, showed a strong induction in HR individuals. From the OeAOX2 full-length gene, alleles and effective polymorphisms were distinguished and analysed in the cross progeny, which were segregated based on rooting. The results revealed a possible correlation between two single nucleotide polymorphisms of OeAOX2 gene and rooting ability.

  2. Polymorphisms of apolipoprotein E and angiotensin-converting enzyme genes and carotid atherosclerosis in heavy drinkers.

    PubMed

    Bednarska-Makaruk, Małgorzata; Rodo, Maria; Markuszewski, Cezary; Rozenfeld, Anna; Swiderska, Malgorzata; Habrat, Bogusław; Wehr, Hanna

    2005-01-01

    To investigate the influence of apolipoprotein E (APOE) and angiotensin-converting enzyme (ACE) gene polymorphisms on carotid artery atherosclerosis in alcoholism. Polymorphism of both genes was identified by DNA analysis in 130 male alcohol-dependent patients. Intima-media thickness (IMT) was measured ultrasonographically. Multivariate regression analysis showed that of all the known risk factors the greatest impact on carotid atherosclerosis in alcoholics was exerted by age, hypertension, LDL cholesterol and fasting plasma glucose levels. Subjects carrying the APO E epsilon4 allele were more liable to develop atherosclerotic changes in carotid arteries compared with subjects with the epsilon3/3 genotype, which showed statistical significance in patients under 50 years of age. No association was shown between ACE I/D polymorphism and carotid atherosclerosis. APO E polymorphism can increase the risk of carotid atherosclerosis development in an alcoholic subject. The association of the APO E epsilon4 allele with carotid atherosclerosis was significant in younger patients. Since the elevated carotid IMT is considered to be a good marker of increased risk of generalized atherosclerosis the consequences could involve both cardiac and cerebrovascular events.

  3. Plasma ghrelin levels and polymorphisms of ghrelin gene in Chinese obese children and adolescents.

    PubMed

    Zhu, J F; Liang, L; Zou, C C; Fu, J F

    2010-09-01

    To evaluate the role of fasting plasma ghrelin levels [ln(ghrelin)] and polymorphisms of ghrelin gene in Chinese obese children. Genotyping for ghrelin polymorphism was performed in 230 obese and 100 normal weight children. Among them, plasma ghrelin levels were measured in 91 obese and 23 health subjects. (1) Bivariate correlation analysis showed the ln(ghrelin) was inversely correlated with abnormality of glucose metabolism (r = -0.240, P = 0.023). Stepwise multiple regression analysis showed that abnormality of glucose metabolism was an independent determinant of plasma ghrelin levels (P = 0.023). (2) There was no difference in frequency of Leu72Met polymorphisms between obese and control groups (36.09 vs. 41.00%). Ghrelin is associated with obesity in childhood, especially associated with the glucose homeostasis. Lower ghrelin levels might be a result of obesity, but not a cause of obesity. The Leu72Met polymorphism of ghrelin gene is not associated with obesity and metabolic syndrome in Chinese children.

  4. Methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in chronic myeloid leukemia: an Egyptian study.

    PubMed

    Khorshied, Mervat Mamdooh; Shaheen, Iman Abdel Mohsen; Abu Khalil, Reham E; Sheir, Rania Elsayed

    2014-01-01

    Methylenetetrahydrofolate reductase (MTHFR) gene plays a pivotal role in folate metabolism. Several genetic variations in MTHFR gene as MTHFR-C677T and MTHFR-A1298C result in decreased MTHFR activity, which could influence efficient DNA methylation and explain susceptibility to different cancers. The etiology of chronic myeloid leukemia (CML) is obscure and little is known about individual's susceptibility to CML. In order to assess the influence of these genetic polymorphisms on the susceptibility to CML and its effect on the course of the disease among Egyptians, we performed an age-gender-ethnic matched case-control study. The study included 97 CML patients and 130 healthy controls. Genotyping of MTHFR-C677T and -A1298C was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The results showed no statistical difference in the distribution of MTHFR-C677T and -A1298C polymorphic genotypes between CML patients and controls. The frequency of MTHFR 677-TT homozygous variant was significantly higher in patients with accelerated/blastic transformation phase when compared to those in the chronic phase of the disease. In conclusion, our study revealed that MTHFR-C677T and -A1298C polymorphisms could not be considered as genetic risk factors for CML in Egyptians. However, MTHFR 677-TT homozygous variant might be considered as a molecular predictor for disease progression.

  5. Effect of Interleukin-18 Gene Polymorphisms on Sensitization to Wheat Flour in Bakery Workers

    PubMed Central

    Kim, Seung-Hyun; Hur, Gyu-Young; Jin, Hyun Jung; Choi, Hyunna

    2012-01-01

    Lower respiratory symptoms in bakery workers may be induced by wheat flour and endotoxins. We hypothesized that endotoxins from wheat flour may stimulate innate immunity and that interleukin-18 (IL-18) gene polymorphisms may affect their regulatory role in innate immune responses to endotoxins. To investigate the genetic contribution of IL-18 to sensitization to wheat flour, we performed a genetic association study of IL-18 in Korean bakery workers. A total of 373 bakery workers undertook a questionnaire regarding work-related symptoms. Skin prick tests with common and occupational allergens were performed and specific antibodies to wheat flour were measured by ELISA. Three polymorphisms of the IL-18 gene (-607A/C, -137G/C, 8674C/G) were genotyped, and the functional effects of the polymorphisms were analyzed using the luciferase reporter assay. Genotypes of -137G/C (GC or CC) and haplotype ht3 [ACC] showed a significant association with the rate of sensitization to wheat flour. Luciferase activity assay indicated ht3 [AC] as a low transcript haplotype. In conclusion, the regulatory role of IL-18 in lipopolysaccharide-induced responses in bakery workers may be affected by this polymorphism, thus contributing to the development of sensitization to wheat flour and work-related respiratory symptoms. PMID:22468101

  6. Association between DAOA gene polymorphisms and the risk of schizophrenia, bipolar disorder and depressive disorder.

    PubMed

    Tan, Jinjing; Lin, Yu; Su, Li; Yan, Yan; Chen, Qing; Jiang, Haiyun; Wei, Qiugui; Gu, Lian

    2014-06-03

    Schizophrenia (SCZ), bipolar disorder (BD) and depressive disorder (DD) are common psychiatric disorders, which show common genetic vulnerability. Previous gene-disease association studies have reported correlations between d-amino acid oxidase activator (DAOA) gene polymorphisms and the three psychiatric disorders. However, the findings were contradictory. A meta-analysis was therefore conducted to provide more robust investigations into DAOA polymorphisms and the risk of SCZ, BD and DD. This meta-analysis recruited 46 published studies up to July 2013, including 17,515 cases and 25,189 controls. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the association between three specific DAOA SNPs and SCZ, BD and DD. Publication bias was tested by Begg's test and funnel plot, and heterogeneity was assessed by the Cochran's chi-square-based Q statistic and the inconsistency index (I(2)). Moreover, the robustness of the findings was estimated by cumulative meta-analysis. DAOA genetic polymorphisms (M15, M18 and M23) were not found to confer a statistically significant increased risk of SCZ, BD or DD in the overall sample, or in Caucasians and Asians following subgroup analysis. The current study indicated that M15, M18 and M23 might not be the risk factor for SCZ, BD or DD. However, further studies are required to provide robust evidence to estimate the association between DAOA polymorphisms and psychiatric disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2015-12-01

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

  8. 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.

  9. Impacts of CA9 gene polymorphisms on urothelial cell carcinoma susceptibility and clinicopathologic characteristics in Taiwan.

    PubMed

    Wang, Shian-Shiang; Liu, Yu-Fan; Ou, Yen-Chuan; Chen, Chuan-Shu; Li, Jian-Ri; Yang, Shun-Fa

    2013-01-01

    Carbonic anhydrase 9 (CA9) is reportedly overexpressed in several types of carcinomas and is generally considered a marker of malignancy. The current study explored the effect of CA9 gene polymorphisms on the susceptibility of developing urothelial cell carcinoma (UCC) and the clinicopathological status. A total of 442 participants, including 221 healthy people and 221 patients with UCC, were recruited for this study. Four single-nucleotide polymorphisms (SNPs) of the CA9 gene were assessed by a real-time PCR with the TaqMan assay. After adjusting for other co-variants, the individuals carrying at least one A allele at CA9 rs1048638 had a 2.303-fold risk of developing UCC than did wild-type (CC) carriers. Furthermore, UCC patients who carried at least one A allele at rs1048638 had a higher invasive stage risk (p< 0.05) than did patients carrying the wild-type allele. Moreover, among the UCC patients with smoker, people with at least one A allele of CA9 polymorphisms (rs1048638) had a 4.75-fold (95% CI = 1.204-18.746) increased risk of invasive cancer. The rs1048638 polymorphic genotypes of CA9 might contribute to the prediction of susceptibility to and pathological development of UCC. This is the first study to provide insight into risk factors associated with CA9 variants in carcinogenesis of UCC in Taiwan.

  10. Polymorphism of Glucokinase Gene in Non-Insulin Dependent Diabetes Mellitus

    PubMed Central

    Kim, Deog-Yoon; Choi, Jung-Hee; Woo, Jeong-Taek; Paeng, Jeong-Ryung; Yang, In-Myung; Kim, Sung-Woon; Kim, Jin-Woo; Kim, Young-Seol; Kim, Kwang-Won; Choi, Young-Kil

    1994-01-01

    Several lines of evidence suggest a strong genetic component to NIDDM. To clarify the role of glucokinase gene in the development of NIDDM, restriction fragment length polymorphism (RFLP) of glucokinase gene and 3′ microsatellite polymorphism analyses by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) were performed in NIDDM and control subjects. Compared to NIDDM with 1.3 kb allele/Pvu I digestion of glucokinase, 10% of NIDDM did not demonstrate 1.3 kb allele and these patients were charcterized by increased insulin secretion. In 3′ microsatellite polymorphism analysis, autoradiography of PCR products revealed three different alleles, including Z, Z+2 and Z+4. Z was the most common allele in both NIDDM and nondiabetic controls. There was no significant allele associated with NIDDM. Frequency of the homozygote Z/Z genotype was significantly lower in NIDDM subjects (16.7%) compared to normal control (46.7%) (p<0.05). There was no difference in clinical findings according to 3′ microsatellite genotypes in NIDDM. These data suggest that there does not appear to be a significant glucokinase allele associated with NIDDM but Z/Z genotype may play a suppressive role in the pathogenesis of a certain type of NIDDM in Korea. Further studies may be required to identify the molecular basis of this association. PMID:7913622

  11. Cyclooxygenase 2 gene polymorphisms and chronic periodontitis in a North Indian population: a pilot study

    PubMed Central

    Daing, Anika; Singh, Sarvendra Vikram; Saimbi, Charanjeet Singh; Khan, Mohammad Akhlaq

    2012-01-01

    Purpose Cyclooxygenase (COX) enzyme catalyzes the production of prostaglandins, which are important mediators of tissue destruction in periodontitis. Single nucleotide polymorphisms of COX2 enzyme have been associated with increasing susceptibility to inflammatory diseases. The present study evaluates the association of two single nucleotide polymorphisms in COX2 gene (-1195G>A and 8473C>T) with chronic periodontitis in North Indians. Methods Both SNPs and their haplotypes were used to explore the associations between COX2 polymorphisms and chronic periodontitis in 56 patients and 60 controls. Genotyping was done by polymerase chain reaction followed by restriction fragment length polymorphism. Chi-square test and logistic regression analysis were performed for association analysis. Results By the individual genotype analysis, mutant genotypes (GA and AA) of COX2 -1195 showed more than a two fold risk (odds ratio [OR]>2) and COX2 8473 (TC and CC) showed a reduced risk for the disease, but the findings were not statistically significant. Haplotype analysis showed that the frequency of the haplotype AT was higher in the case group and a significant association was found for haplotype AT (OR, 1.79; 95% confidence interval, 1.03 to 3.11; P=0.0370) indicating an association between the AT haplotype of COX2 gene SNPs and chronic periodontitis. Conclusions Individual genotypes of both the SNPs were not associated while haplotype AT was found to be associated with chronic periodontitis in North Indians. PMID:23185695

  12. 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.

  13. Alcohol and aggressive behavior in men--moderating effects of oxytocin receptor gene (OXTR) polymorphisms.

    PubMed

    Johansson, A; Bergman, H; Corander, J; Waldman, I D; Karrani, N; Salo, B; Jern, P; Algars, M; Sandnabba, K; Santtila, P; Westberg, L

    2012-03-01

    We explored if the disposition to react with aggression while alcohol intoxicated was moderated by polymorphic variants of the oxytocin receptor gene (OXTR). Twelve OXTR polymorphisms were genotyped in 116 Finnish men [aged 18-30, M = 22.7, standard deviation (SD) = 2.4] who were randomly assigned to an alcohol condition in which they received an alcohol dose of 0.7 g pure ethanol/kg body weight or a placebo condition. Aggressive behavior was measured using a laboratory paradigm in which it was operationalized as the level of aversive noise administered to a fictive opponent. No main effects of the polymorphisms on aggressive behavior were found after controlling for multiple testing. The interactive effects between alcohol and two of the OXTR polymorphisms (rs4564970 and rs1488467) on aggressive behavior were nominally significant and remained significant for the rs4564970 when controlled for multiple tests. To the best of our knowledge, this is the first experimental study suggesting interactive effects of specific genetic variants and alcohol on aggressive behavior in humans. © 2011 The Authors. Genes, Brain and Behavior © 2011 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

  14. Interleukin-10 -1082 G/A gene polymorphisms in Egyptian children with CAP

    PubMed Central

    Azab, Seham F.; Abdalhady, Mohamed A.; Elsaadany, Hosam F.; Elkomi, Mohamed A.; Elhindawy, Eman M.; Sarhan, Dina T.; Salam, Mohamed M.A.; Allah, Mayy A.N.; Emam, Ahmed A.; Noah, Maha A.; Abdelsalam, Nasser I.; Abdellatif, Sawsan H.; Rass, Anwar A.; Ismail, Sanaa M.; Gheith, Tarek; Aziz, Khalid A.; Hamed, Mohammed E.; Abdelrahman, Hind M.; Ahmed, Ahmed R.; Nabil, Rehab M.; Abdulmaksoud, Rehab S.; Yousef, Hala Y.

    2016-01-01

    Abstract Community-acquired pneumonia (CAP) is one of the leading causes of death worldwide. Cytokines are involved in the pathogenesis of CAP. To date, only a few studies concerned the association of interleukin-10 (IL-10) gene polymorphisms with CAP. In this study, we aimed to investigate whether the -1082(G/A) polymorphism in the promoter region of the IL-10 gene is involved in susceptibility to and the outcome of CAP, and we also measured the serum level of IL-10 to assess its relation to such polymorphism. This was a case–control study included 100 patients with CAP, and matched with age, gender, and ethnicity of 100 healthy control children. IL-10 -1082(G/A) gene polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism, while the serum IL-10 levels were measured by ELISA method. Compared to the controls subjects, the frequencies of the IL-10 -1082 AA genotype and A allele were observed to be overrepresented in patients with CAP (51%; odds ratio [OR] = 2.8; 95% confidence interval [CI]: 1.5–5.3 for the AA genotype; P < 0.01) and (70%; OR: 1.95; 95% CI: 1.27–3.00 for the A allele; P < 0.01, respectively). We found that patients with the GG genotype had significantly higher serum IL-10 levels (46.7 ± 9.5 pg/mL) compared to those with AG genotype (21.8 ± 4.5 pg/mL) and AA genotype (11.5 ± 3.3 pg/mL); P < 0.01, respectively. Our data revealed a significant positive association between the -1082 GG genotype and susceptibility to severe sepsis, acute respiratory failure, and hospital mortality (OR: 3.8; 95% CI: 1.3–11.2; P < 0.01). We demonstrate for the first time, to the best of our knowledge, that IL-10 -1082 (G/A) gene polymorphism may contribute to susceptibility to CAP in Egyptian children. Moreover, we observed that the presence of a G allele or GG genotype at the -1082 position of the promoter region of the IL-10 gene constitute risk factors for developing severe sepsis

  15. Association between Apolipoprotein C-III Gene Polymorphisms and Coronary Heart Disease: A Meta-analysis.

    PubMed

    Zhang, Jing-Zhan; Xie, Xiang; Ma, Yi-Tong; Zheng, Ying-Ying; Yang, Yi-Ning; Li, Xiao-Mei; Fu, Zhen-Yan; Dai, Chuan-Fang; Zhang, Ming-Ming; Yin, Guo-Ting; Liu, Fen; Chen, Bang-Dang; Gai, Min-Tao

    2016-01-01

    Polymorphisms in the apolipoprotein C-III (APOC3) gene have been reported to be associated with coronary heart disease (CHD), but the data so far have been conflicting. To derive a more precise estimation of these associations, we performed a meta-analysis to investigate the three main polymorphisms (SstI, T-455C, C-482T) of APOC3 in all published studies. Databases including PubMed, Web of Science, Wanfang, SinoMed and CNKI were systematically searched. The association was assessed using odds ratios (ORs) with 95% confidence intervals (CIs). The statistical analysis was performed using Review Manager 5.3.3 and Stata 12.0. A total of 31 studies have been identified. The pooled odds ratio (OR) for the association between the APOC3 gene polymorphisms and CHD and its corresponding 95% confidence interval (95% CI) were evaluated by random or fixed effect models. A statistical association between APOC3 SstI polymorphism and CHD susceptibility was observed under an allelic contrast model (P= 0.003, OR = 1.14, 95% CI = 1.05-1.24), dominant genetic model (P= 0.01, OR = 1.14, 95% CI = 1.03-1.26), and recessive genetic model (P= 0.02, OR = 1.35, 95% CI = 1.06-1.71), respectively. A significant association between the APOC3 T-455C polymorphism and CHD was also detected under an allelic contrast (P < 0.0001, OR = 1.19, 95% CI = 1.10-1.29), dominant genetic model (P= 0.0003, OR = 1.24, 95% CI = 1.11-1.39) and recessive genetic model (P= 0.04, OR = 1.30, 95% CI = 1.01-1.67). No significant association between the APOC3 C-482T polymorphism and CHD was found under an allelic model (P= 0.94, OR = 1.00, 95% CI = 0.93-1.08), dominant genetic model (P= 0.20, OR = 1.07, 95% CI = 0.97-1.18) or recessive genetic model (P= 0.13, OR = 0.90, 95% CI = 0.79-1.03). This meta-analysis revealed that the APOC3 SstI and T-455C polymorphisms significantly increase CHD susceptibility. No significant association was observed between the APOC3 C-482T polymorphism and CHD susceptibility.

  16. Association between Apolipoprotein C-III Gene Polymorphisms and Coronary Heart Disease: A Meta-analysis

    PubMed Central

    Zhang, Jing-Zhan; Xie, Xiang; Ma, Yi-Tong; Zheng, Ying-Ying; Yang, Yi-Ning; Li, Xiao-Mei; Fu, Zhen-Yan; Dai, Chuan-Fang; Zhang, Ming-Ming; Yin, Guo-Ting; Liu, Fen; Chen, Bang-Dang; Gai, Min-Tao

    2016-01-01

    Polymorphisms in the apolipoprotein C-III (APOC3) gene have been reported to be associated with coronary heart disease (CHD), but the data so far have been conflicting. To derive a more precise estimation of these associations, we performed a meta-analysis to investigate the three main polymorphisms (SstI, T-455C, C-482T) of APOC3 in all published studies. Databases including PubMed, Web of Science, Wanfang, SinoMed and CNKI were systematically searched. The association was assessed using odds ratios (ORs) with 95% confidence intervals (CIs). The statistical analysis was performed using Review Manager 5.3.3 and Stata 12.0. A total of 31 studies have been identified. The pooled odds ratio (OR) for the association between the APOC3 gene polymorphisms and CHD and its corresponding 95% confidence interval (95% CI) were evaluated by random or fixed effect models. A statistical association between APOC3 SstI polymorphism and CHD susceptibility was observed under an allelic contrast model (P= 0.003, OR = 1.14, 95% CI = 1.05-1.24), dominant genetic model (P= 0.01, OR = 1.14, 95% CI = 1.03-1.26), and recessive genetic model (P= 0.02, OR = 1.35, 95% CI = 1.06-1.71), respectively. A significant association between the APOC3 T-455C polymorphism and CHD was also detected under an allelic contrast (P < 0.0001, OR = 1.19, 95% CI = 1.10-1.29), dominant genetic model (P= 0.0003, OR = 1.24, 95% CI = 1.11-1.39) and recessive genetic model (P= 0.04, OR = 1.30, 95% CI = 1.01-1.67). No significant association between the APOC3 C-482T polymorphism and CHD was found under an allelic model (P= 0.94, OR = 1.00, 95% CI = 0.93-1.08), dominant genetic model (P= 0.20, OR = 1.07, 95% CI = 0.97-1.18) or recessive genetic model (P= 0.13, OR = 0.90, 95% CI = 0.79-1.03). This meta-analysis revealed that the APOC3 SstI and T-455C polymorphisms significantly increase CHD susceptibility. No significant association was observed between the APOC3 C-482T polymorphism and CHD susceptibility. PMID:26816662

  17. Association of vitamin D receptor gene polymorphisms with susceptibility to childhood asthma: A meta-analysis.

    PubMed

    Zhao, Dong-Dong; Yu, Dan-Dan; Ren, Qiong-Qiong; Dong, Bao; Zhao, Feng; Sun, Ye-Huan

    2017-04-01

    As for the association of vitamin D receptor (VDR) gene polymorphisms with susceptibility to pediatric asthma, results of published studies yielded conflicts. A systematic review was conducted on the relationship between childhood asthma and VDR gene polymorphisms, including ApaI (rs7975232), BsmI (rs1544410), FokI (rs2228570), and TaqI (rs731236). PubMed, Web of Science, CBM (Chinese Biomedical Database), CNKI (China National Knowledge Infrastructure), and Wanfang (Chinese) database were searched for relevant studies. Pooled odds ratios (OR) with 95% confidence interval (CI) were calculated. Overall results suggested that there was a statistically significant association between ApaI polymorphism and childhood asthma in homozygote model (OR = 1.674, 95%CI = 1.269-2.208, P < 0.001) and allele model (OR = 1.221, 95%CI = 1.084-1.375, P = 0.001). Stratification by ethnicity revealed a statistical association in Asians (OR = 1.389, 95%CI = 1.178-1.638, P < 0.001). There was some evidence of an association between BsmI polymorphism and childhood asthma in the homozygote (OR = 1.462, 95%CI = 1.016-2.105, P = 0.041) and allele models (OR = 1.181, 95%CI = 1.006-1.386, P = 0.042). This association reached significance only in the Caucasian group (OR = 1.236, 95%CI = 1.029-1.485, P = 0.023). For FokI, a statistical association was detected in dominant model (OR = 1.281, 95%CI = 1.055-1.555, P = 0.012); this association was significant in allele model (OR = 1.591, 95%CI = 1.052-2.405, P = 0.028) in Caucasian. ApaI polymorphism plays a particular role in childhood asthma in Asians. FokI polymorphism may be connected with pediatric asthma in Caucasian population. And BsmI polymorphism marginally contributes to childhood asthma susceptibility, while there might be no association between TaqI polymorphism and childhood asthma risk. Pediatr Pulmonol. 2017;52:423-429. © 2016 Wiley

  18. Associations between CD24 gene polymorphisms and inflammatory bowel disease: A meta-analysis.

    PubMed

    Huang, Xiao-Li; Xu, Dong-Hua; Wang, Guo-Pin; Zhang, Shu; Yu, Cheng-Gong

    2015-05-21

    To evaluate the relationships between CD24 gene polymorphisms and the risk of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD). The PubMed, Web of Science and Cochrane Library databases were searched (up to May 30, 2014). The search terms "CD24", "inflammatory bowel disease", "Crohn's disease", "Ulcerative colitis", "IBD", "CD" or "UC"; and "polymorphism", "mutation" or "variant" were used. Association studies were limited to the English language, but no limitations in terms of race, ethnicity or geographic area were employed. Stata SE12 software was used to calculate the pooled odds ratios (ORs) with 95% confidence intervals (CIs). P < 0.05 was considered statistically significant. The information was independently extracted from each eligible study by two investigators. Two common polymorphisms, C170T (rs8734) and TG1527del (rs3838646), in the CD24 gene were assessed. A total of three case-control studies including 2342 IBD patients and 1965 healthy controls were involved in this meta-analysis. The patients and controls were from Caucasian cohorts. The three articles included in this meta-analysis all conformed to Hardy-Weinberg equilibrium. This meta-analysis revealed that there were no significant associations between the two CD24 polymorphisms and the risk for IBD (all P > 0.05). However, in a disease subgroup analysis, we found that the CD24 C170T polymorphism was associated with an increased risk of UC in a dominant model (OR = 1.79, 95%CI: 1.15-2.77, P = 0.009) and an additive model (OR = 1.87, 95%CI: 1.19-2.93, P = 0.007), but this relationship was not present for CD. The CD24 TG1570del polymorphism was significantly associated with CD in the additive model (OR = 1.24, 95%CI: 1.01-1.52, P = 0.037). Our findings provide evidence that the CD24 C170T polymorphism might contribute to the susceptibility to UC, and the CD24 TG1527del polymorphism might be associated with the risk of CD.

  19. Association between the KRAS Gene Polymorphisms and Papillary Thyroid Carcinoma in a Chinese Han Population.

    PubMed

    Ning, Lifeng; Rao, Wenwang; Yu, Yaqin; Liu, Xiaoli; Pan, Yuchen; Ma, Yuan; Liu, Rui; Zhang, Shangchao; Sun, Hui; Yu, Qiong

    2016-01-01

    Several studies have reported the association between MAPK signaling pathway gene polymorphisms and papillary thyroid carcinoma (PTC). KRAS gene, an oncogene from the mammalian RAS gene family plays an important role in the MAPK pathway. This study aimed to identify the potential association of KRAS gene polymorphisms with susceptibility to PTC in a Han Chinese population. A total of 861 patients with PTC, 562 disease controls with nodular goiter and 897 healthy controls were recruited. Four tagSNP polymorphisms (rs12427141, rs712, rs7315339 and rs7960917) of KRAS gene were genotyped by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) . Statistical analyses and haplotype estimations were conducted using Haploview and Unphased softwares. Only significant differences were observed in genotypic frequencies of the rs7315339 polymorphism (χ 2 =7.234, df=2, p=0.027) between PTC and disease controls. Statistically significant differences in both allelic and genotypic genotypes frequencies for rs712 (Genotype, χ 2 =8.258, p=0.016) and rs12427141 (Allele, χ 2 =3.992, p=0.046; Genotype, χ 2 =8.140, p=0.017) were observed between PTC patients and controls. Haplotype analyses revealed higher frequencies of GA and TA haplotypes (p=0.039 and p=0.003, respectively) from rs712- rs12427141 (two-SNP) or TGA and TTG haplotype containing the alleles from rs7960917, rs712 and rs12427141, as well as the GAT haplotype containing the alleles from rs712, rs12427141 and rs7315339 in PTC patients than in healthy controls (p=0.042, p=0.037, p=0.027, respectively). Inversely, the haplotype TTA from rs7960917, rs712 and rs12427141 or the haplotype TAC from rs712, rs12427141 and rs7315339 was significantly less frequent in the PTC patients than in normal control (p=0.003, p=0.003, respectively). These findings suggest the role of these KRAS gene variants in susceptibility to PTC. Moreover, significant differences of the KRAS gene polymorphisms may

  20. Association of ATG5 Gene Polymorphisms With Behçet's Disease and ATG10 Gene Polymorphisms With VKH Syndrome in a Chinese Han Population.

    PubMed

    Zheng, Minming; Yu, Hongsong; Zhang, Lijun; Li, Hua; Liu, Yunjia; Kijlstra, Aize; Yang, Peizeng

    2015-12-01

    This study was conducted to explore the association of autophagy-related genes (ATGs) single nucleotide polymorphisms (SNPs) with Behçet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Chinese Han population. A two-stage association study was carried out in 940 BD, 1061 VKH, and 2007 healthy controls. Genotyping for genetic variants of 10 autophagy family genes (ATG5, ATG7, ATG10, ATG16L1, IRGM, LKKR2, ATG2A, DAP, ULK1, and TSC1) was performed using PCR-restriction fragment length polymorphism (PCR-RFLP) or TaqMan SNP assays. Gene expression was quantified by real-time PCR. In the cohort of BD patients, we observed that the TT genotype of rs573775/ATG5 decreased susceptibility to BD (Pc = 8.35 × 10-6, OR = 0.490). In the case of VKH patients, the AC genotype of rs4703863/ATG10 increased susceptibility to VKH syndrome (Pc = 9.94 × 10-5, OR = 1.444), whereas the A allele and AA genotype of rs4703863 (Pc = 7.06 × 10-5, OR = 0.745; Pc = 6.34 × 10-6, OR = 0.669, respectively) acted as protective factors for VKH. Functional experiments showed an increased ATG5 expression by LPS stimulated PBMCs in TT cases of rs573775 compared with controls. The level of ATG5 mRNA in active BD patients not receiving immunosuppression was significantly higher than that in healthy controls. This study demonstrated an association of ATG5 rs573775 with BD and ATG10 rs4703863 with VKH syndrome in a Chinese Han population. Furthermore, a variant of the ATG5 gene was shown to be correlated with ATG5 expression.

  1. [Association between polymorphisms of XPD gene and susceptibility to chronic benzene poisoning].

    PubMed

    Huang, Hui-long; Xu, Jian-ning; Wang, Quan-kai; Wang, Ya-wen; Yang, Min; Chen, Yan; Li, Gui-lan

    2006-07-01

    To explore the relationship between genetic polymorphisms of XPD gene and susceptibility to chronic benzene poisoning. A case control study was conducted. Eighty patients diagnosed with chronic benzene poisoning and 62 workers occupationally exposed to benzene who were engaged in the same working time and job title as patients were investigated. PCR-RFLP was used for detecting the single nucleotide polymorphisms (SNPs) on codon156, codon312 and codon751 of XPD gene. There was a 2.903 times (95% CI: 1.054 - 7.959, P = 0.039 2) increased risk of chronic benzene poisoning in the subjects carrying XPD 751Gln variant allele compared with those carrying XPD 751Lys/Lys genotype, after adjusted for sex, length of service, smoking and drinking status. The subjects with XPD 751Gln variant allele are more susceptive to benzene.

  2. Androgen Receptor Gene Polymorphisms and Alterations in Prostate Cancer: Of Humanized Mice and Men

    PubMed Central

    Robins, Diane M.

    2011-01-01

    Germline polymorphisms and somatic mutations of the androgen receptor (AR) have been intensely investigated in prostate cancer but even with genomic approaches their impact remains controversial. To assess the functional significance of AR genetic variation, we converted the mouse gene to the human sequence by germline recombination and engineered alleles to query the role of a polymorphic glutamine (Q) tract implicated in cancer risk. In a prostate cancer model, AR Q tract length influences progression and castration response. Mutation profiling in mice provides direct evidence that somatic AR variants are selected by therapy, a finding validated in human metastases from distinct treatment groups. Mutant ARs exploit multiple mechanisms to resist hormone ablation, including alterations in ligand specificity, target gene selectivity, chaperone interaction and nuclear localization. Regardless of their frequency, these variants permute normal function to reveal novel means to target wild type AR and its key interacting partners. PMID:21689727

  3. No Association between Oxytocin Receptor (OXTR) Gene Polymorphisms and Experimentally Elicited Social Preferences

    PubMed Central

    Apicella, Coren L.; Cesarini, David; Johannesson, Magnus; Dawes, Christopher T.; Lichtenstein, Paul; Wallace, Björn; Beauchamp, Jonathan; Westberg, Lars

    2010-01-01

    Background Oxytocin (OXT) has been implicated in a suite of complex social behaviors including observed choices in economic laboratory experiments. However, actual studies of associations between oxytocin receptor (OXTR) gene variants and experimentally elicited social preferences are rare. Methodology/Principal Findings We test hypotheses of associations between social preferences, as measured by behavior in two economic games, and 9 single nucleotide polymorphisms (SNPs) of the OXTR gene in a sample of Swedish twins (n = 684). Two standard economic games, the dictator game and the trust game, both involving real monetary consequences, were used to elicit such preferences. After correction for multiple hypothesis testing, we found no significant associations between any of the 9 single nucleotide polymorphisms (SNPs) and behavior in either of the games. Conclusion We were unable to replicate the most significant association reported in previous research between the amount donated in a dictator game and an OXTR genetic variant. PMID:20585395

  4. RETRACTED: Association of the ACE I/D gene polymorphism with sepsis susceptibility and sepsis progression.

    PubMed

    Yang, Chun-Hua; Zhou, Tian-Biao

    2015-12-01

    This article has been included in a multiple retraction: Chun-Hua Yang and Tian-Biao Zhou Association of the ACE I/D gene polymorphism with sepsis susceptibility and sepsis progression Journal of Renin-Angiotensin-Aldosterone System 1470320314568521, first published on February 3, 2015 doi: 10.1177/1470320314568521 This article has been retracted at the request of the Editors and the Publisher. After conducting a thorough investigation, SAGE found that the submitting authors of a number of papers published in the Journal of the Renin-Angiotensin Aldosterone System ( JRAAS) (listed below) had supplied fabricated contact details for their nominated reviewers. The Editors accepted these papers based on the reports supplied by the individuals using these fake reviewer email accounts. After concluding that the peer review process was therefore seriously compromised, SAGE and the journal Editors have decided to retract all affected articles. Online First articles (these articles will not be published in an issue) Wenzhuang Tang, Tian-Biao Zhou, and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563426, first published on December 18, 2014 doi: 10.1177/1470320314563426 Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang, and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563424, first published on December 18, 2014 doi: 10.1177/1470320314563424 Weiqiang Zhong, Zongpei Jiang, and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population Journal of Renin-Angiotensin-Aldosterone System 1470320314566019, first published on January 26, 2015 doi: 10.1177/1470320314566019 Tian-Biao Zhou, Xue-Feng Guo, Zongpei

  5. No association between oxytocin receptor (OXTR) gene polymorphisms and experimentally elicited social preferences.

    PubMed

    Apicella, Coren L; Cesarini, David; Johannesson, Magnus; Dawes, Christopher T; Lichtenstein, Paul; Wallace, Björn; Beauchamp, Jonathan; Westberg, Lars

    2010-06-16

    Oxytocin (OXT) has been implicated in a suite of complex social behaviors including observed choices in economic laboratory experiments. However, actual studies of associations between oxytocin receptor (OXTR) gene variants and experimentally elicited social preferences are rare. We test hypotheses of associations between social preferences, as measured by behavior in two economic games, and 9 single nucleotide polymorphisms (SNPs) of the OXTR gene in a sample of Swedish twins (n = 684). Two standard economic games, the dictator game and the trust game, both involving real monetary consequences, were used to elicit such preferences. After correction for multiple hypothesis testing, we found no significant associations between any of the 9 single nucleotide polymorphisms (SNPs) and behavior in either of the games. We were unable to replicate the most significant association reported in previous research between the amount donated in a dictator game and an OXTR genetic variant.

  6. The evaluation of angiotensin-converting enzyme (ACE) gene I/D and IL-4 gene intron 3 VNTR polymorphisms in coronary artery disease.

    PubMed

    Basol, Nursah; Celik, Atac; Karakus, Nevin; Ozturk, Sibel Demir; Ozsoy, Sibel Demir; Yigit, Serbulent

    2014-01-01

    Genetic polymorphism is a strong risk factor for coronary artery disease (CAD). In the present study, our aim was to evaluate angiotensin-converting enzyme (ACE) gene I/D polymorphism and interleukin-4 (IL-4) gene Intron 3 variable number of tandem repeat (VNTR) polymorphism in CAD. One hundred and twenty-four CAD patients and one hundred and twenty-three controls were enrolled. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR) analyses. The risk associated with inheriting the combined genotypes for the two polymorphisms were evaluated and it was found that the individuals who were P2P2-homozygous at IL-4 gene intron 3 VNTR and DD-homozygous at ACE gene I/D have a higher risk of developing CAD. Although, there is no correlation between IL4 VNTR polymorphism and ACE gene polymorphism and CAD, there is a strong association between CAD and co-existence of IL-4 VNTR and ACE gene polymorphisms in the Turkish population. Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  7. Porcine NAMPT gene: search for polymorphism, mapping and association studies.

    PubMed

    Cepica, S; Bartenschlager, H; Ovilo, C; Zrůstová, J; Masopust, M; Fernández, A; López, A; Knoll, A; Rohrer, G A; Snelling, W M; Geldermann, H

    2010-12-01

    NAMPT encodes an enzyme catalysing the rate-limiting step in NAD biosynthesis. The extracellular form of the enzyme is known as adipokine visfatin. We detected SNP AM999341:g.669T>C (referred to as 669T>C) in intron 9 and SNP FN392209:g.358A>G (referred to as 358A>G) in the promoter of the gene. RH mapping linked the gene to microsatellite SW944. Linkage analysis placed the gene on the current USDA – USMARC linkage map at position 92 cM on SSC9. Association analyses were performed in a wild boar × Meishan F2 family (W × M), with 45 traits recorded (growth and fattening, fat deposition, muscling, meat quality, stress resistance and other traits), and in a commercial Landrace × Chinese-European (LCE) synthetic population with records for 15 traits (growth, fat deposition, muscling, intramuscular fat, meat colour and backfat fatty acid content). In the W × M, SNP 669T>C was associated with muscling, fat deposition, growth and fattening, meat quality and other traits and in the LCE with muscling, meat quality and backfat fatty acid composition. In the W × M, SNP 358A>G was associated with muscling, fat deposition, growth and other traits. After correction for multiple testing, the NAMPT haplotypes were associated in the W × M with, in descending order, muscling (q = 0.0056), growth (q = 0.0056), fat deposition (q = 0.0109), fat-to-meat ratio (q = 0.0135), cooling losses (q = 0.0568) and longissimus pHU (q = 0.0695). The SNPs are hypothesized to be in linkage disequilibrium with a causative mutation affecting energy metabolism as a whole rather than fat metabolism alone.

  8. Association of GABA(B)R1 receptor gene polymorphism with obstructive sleep apnea syndrome.

    PubMed

    Bayazit, Yildirim A; Yilmaz, Metin; Kokturk, Oguz; Erdal, M Emin; Ciftci, Tansu; Gokdogan, Tuba; Kemaloglu, Yusuf; Ileri, Fikret

    2007-01-01

    GABA(B)R (gamma-amino butyric acid B receptor)-mediated neurotransmission has been implicated in the pathophysiology of a variety of neuropsychiatric disorders. GABA(B)R1 gene variants were identified by single-strand conformation analysis. The nucleotide exchanges cause a substitution of alanine to valine in exon 1a1 (Ala20Val), a substitution of glycine to serine in exon 7 (Gly489Ser) and a silent C to G nucleotide exchange encoding the amino acid phenylalanine in exon 11 (Phe658Phe). The significance of GABA(B)R1a gene polymorphism in obstructive sleep apnea syndrome (OSAS) as well as the association of these polymorphisms with the polysomnography findings in OSAS patients are not known. In this study, we aimed to assess the significance of 3 different GABA(B)R1 gene polymorphisms (Ala20Val, Gly489Ser and Phe658Phe) in OSAS. Seventy-five patients (23 female and 52 male) with OSAS and 99 healthy volunteers (51 female, 48 male) were included in the study to assess Ala20Val, Gly489Ser and Phe658Phe polymorphisms of the GABA(B)R1 gene. For the Ala20Val variants, there was no significant difference between the genotypes and allele frequencies of the patients and controls, nor between both genders (p > 0.05). For Phe658Phe polymorphism, there was no significant difference between genotypes and allele frequencies of the patients and controls (p > 0.05). However, the C/C genotype was overrepresented and the T/C genotype was less frequent in male than female patients (p = 0.03). The C/C genotype was overrepresented and the T/C genotype was less frequent in male patients than male controls (p = 0.01). For GABA(B)R1-Gly489Ser polymorphism, all of the patients and controls had G/G genotype. The apnea arousal index scores of the male patients with C/C genotype were significantly higher than in the patients with C/T genotype (p = 0.01). The percent total sleep time in non-REM 1 scores of the male patients with T/T genotype were significantly higher than in the patients with T

  9. 1236 C/T and 3435 C/T polymorphisms of the ABCB1 gene in Mexican breast cancer patients.

    PubMed

    Gutierrez-Rubio, S A; Quintero-Ramos, A; Durán-Cárdenas, A; Franco-Topete, R A; Castro-Cervantes, J M; Oceguera-Villanueva, A; Jiménez-Pérez, L M; Balderas-Peña, L M A; Morgan-Villela, G; Del-Toro-Arreola, A; Daneri-Navarro, A

    2015-02-13

    MDR1, which is encoded by the ABCB1 gene, is involved in multidrug resistance (hydrophobic), as well as the elimination of xenotoxic agents. The association between ABCB1 gene polymorphisms and breast cancer risk in different populations has been described previously; however, the results have been inconclusive. In this study, we examined the association between polymorphisms 3435 C/T and 1236 C/T in the ABCB1 gene and breast cancer development in Mexican women according to their menopausal status and molecular classification. Molecular subtypes as well as allele and genotype frequencies were analyzed. A total of 248 women with initial breast cancer diagnosis and 180 ethnically matched, healthy, unrelated individuals were enrolled. Polymerase chain reaction-restriction fragment length polymorphism was performed to detect polymorphisms 3435 C/T and 1236 C/T in the ABCB1 gene. Premenopausal T allele carriers of the 3435 C/T polymorphism showed a 2-fold increased risk of breast cancer with respect to the reference and postmenopausal groups, as well as triple-negative expression regarding the luminal A/B molecular subrogated subtypes. In contrast, the CT genotype of the 1236 polymorphism was a protective factor against breast cancer. We conclude that the T allele carrier of the 3435 C/T polymorphism in the ABCB1 gene in combination with an estrogen receptor-negative status may be an important risk factor for breast cancer development in premenopausal women.

  10. Association between MASP-2 gene polymorphism and risk of infection diseases: A meta-analysis.

    PubMed

    Fu, Jie; Wang, Jingqiu; Luo, Yanping; Zhang, Lifeng; Zhang, Yuan; Dong, Xinfang; Yu, Hongjuan; Cao, Mingqiang; Ma, Xingming

    2016-11-01

    The role of MASP-2 is vital in the process of complement activation by the lectin pathway. It is generally considered that the functional activation of MASP-2 contribute to the infection disease development process. To analyze the association between MASP-2 functional gene (rs72550870) polymorphism and the infection disease risk by a meta-analysis. Relevant case-control studies were identified by searching Cochrane Library, PubMed, Emabase, DOAJ, CAB Abstracts, CSA, CINAHL, EBSCO, Scopus, Global Health, Index Copernicus, CA, China National Knowledge Infrastructure (CNKI) databases up to 10th January 2016. The data were extracted and the methodological quality of studies were evaluated. The STATA 12.0 software was used to perform statistical analysis. 9 studies were included. There was no significant association between masp-2 gene (p.D120G, rs72550870) polymorphism and the risk of infection disease under the allele model (G vs. A: OR = 0.89, 95%CI = 0.66-1.21)(P = 0.445>0.05) and the recessive model (AG + GG vs.AA: OR = 0.88, 95%CI = 0.65-1.20) (P = 0.428>0.05). This is the first comprehensive meta-analysis indicates that the MASP-2 functional gene (rs72550870) polymorphism is not associated with the infection diseases, and the key functional gene polymorphism of rs72550870 did not increase susceptibility to the infection diseases. Similarly, there were no obvious difference in subgroup analysis based on geographical areas and pathogenic microorganisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. DNA repair gene XRCC1 polymorphisms, smoking, and bladder cancer risk.

    PubMed

    Stern, M C; Umbach, D M; van Gils, C H; Lunn, R M; Taylor, J A

    2001-02-01

    Bladder cancer is the sixth most common cancer in the United States. The main identified risk factor is cigarette smoking, which is estimated to contribute to up to 50% of new cases in men and 20% in women. Besides containing other carcinogens, cigarette smoke is a rich source of reactive oxygen species (ROS) that can induce a variety of DNA damage, some of which is repaired by the base excision repair (BER) pathway. The XRCC1 gene protein plays an important role in BER by serving as a scaffold for other repair enzymes and by recognizing single-strand DNA breaks. Three polymorphisms that induce amino acid changes have been found in codon 194 (exon 6), codon 280 (exon 9), and codon 399 (exon 10) of this gene. We tested whether polymorphisms in XRCC1 were associated with bladder cancer risk and whether this association was modified by cigarette smoking. Therefore, we genotyped for the three polymorphisms in 235 bladder cancer cases and 213 controls who had been frequency matched to cases on age, sex, and ethnicity. We found no evidence of an association between the codon 280 variant and bladder cancer risk [odds ratio (OR), 1.2; 95% confidence interval (CI), 0.6-2.6]. We found some evidence of a protective effect for subjects that carried at least one copy of the codon 194 variant allele relative to those homozygous for the common allele (OR, 0.59; 95% CI, 0.3-1.0). The combined analysis with smoking history suggested a possible gene-exposure interaction; however, the results were not statistically significant. Similarly, for the codon 399 polymorphism, our data suggested a protective effect of the homozygous variant genotype relative to carriers of either one or two copies of the common allele (OR, 0.70; 95% CI, 0.4-1.3), and provided limited evidence, albeit not statistically significant, for a gene-smoking interaction.

  12. Polymorphic Imprinting of SLC38A4 Gene in Bovine Placenta.

    PubMed

    Xu, Da; Zhang, Cui; Li, Junliang; Wang, Guannan; Chen, Weina; Li, Dongjie; Li, Shijie

    2018-05-21

    Imprinted genes are characterized by monoallelic expression that is dependent on parental origin. Comparative analysis of imprinted genes between species is a powerful tool for understanding the biological significance of genomic imprinting. The slc38a4 gene encodes a neutral amino acid transporter and is identified as imprinted in mice. In this study, the imprinting status of SLC38A4 was assessed in bovine adult tissues and placenta using a polymorphism-based approach. Results indicate that SLC38A4 is not imprinted in eight adult bovine tissues including heart, liver, spleen, lung, kidney, muscle, fat, and brain. It was interesting to note that SLC38A4 showed polymorphic status in five heterogeneous placentas, with three exhibiting paternal monoallelic expression and two exhibiting biallelic expression. Monoallelic expression of imprinted genes is generally associated with allele-specific differentially methylation regions (DMRs) of CpG islands (CGIs)-encompassed promoter; therefore, the DNA methylation statuses of three CGIs in the SLC38A4 promoter and exon 1 region were tested in three placentas (two exhibiting paternal monoallelic and one showing biallelic expression of SLC38A4) and their corresponding paternal sperms. Unexpectedly, extreme hypomethylation (< 3%) of the DNA was observed in all the three detected placentas and their corresponding paternal sperms. The absence of DMR in bovine SLC38A4 promoter region implied that DNA methylation of these three CGIs does not directly or indirectly affect the polymorphic imprinting of SLC38A4 in bovine placenta. This suggested other epigenetic features other than DNA methylation are needed in regulating the imprinting of bovine SLC38A4, which is different from that of mouse with respect to a DMR existence at the mouse's slc38a4 promoter region. Although further work is needed, this first characterization of polymorphic imprinting status of SLC38A4 in cattle placenta provides valuable information on investigating

  13. Association study of serotonin transporter gene polymorphisms with obstructive sleep apnea syndrome in Chinese Han population.

    PubMed

    Yue, Weihua; Liu, Huiguo; Zhang, Jishui; Zhang, Xianghui; Wang, Xiaoping; Liu, Tieqiao; Liu, Pozi; Hao, Wei

    2008-11-01

    Since the serotonin (5-HT) is associated with circadian rhythm and breathing regulation, the serotonin transporter (5-HTT), which plays an important role in serotoninergic transmission, might be a strong candidate gene in the pathogenesis of obstructive sleep apnea syndrome (OSAS). To investigate the association of 5-HTT gene polymorphisms with OSAS and clinical characteristics. We genotyped the 5-HTT gene linked polymorphic region (5-HTTLPR) and a variable number of tandem repeats at intron 2 (STin2.VNTR) in 254 OSAS patients and 338 healthy controls in Chinese Han population. In total sample, the 10-repeat allele of STin2.VNTR was significantly associated with OSAS (P = 0.007, OR = 1.72, 95% CI = 1.15-2.58), but no association was found in 5-HTTLPR. In male subjects, both polymorphisms showed significant association with OSAS (Allele L: P = 0.005, OR = 1.44, 95% CI = 1.11 to 1.87; Allele 10: P = 0.002, OR= 1.94, 95% CI = 1.26 to 3.00). Two haplotypes, S-12 and L-10, constructed by the above polymorphisms also revealed significant associations with OSAS (global P-values were 0.020 for total sample and 0.0006 for male subjects, respectively). Male patients carrying the haplotype S-12 showed a significantly lower apnea / hypopnea index (AHI), depressive factor, plasma 5-HT level and 5-hydroxyindolacetic acid (5-HIAA) levels, but higher episodic memory, when compared with non-S-12 carriers (P < 0.05). However, no significant differences were found in excessive daytime sleepiness or other psychological function across haplotype carriers (P > 0.05). These findings support that 5-HTT gene may be involved in susceptibility to OSAS, especially with sex-dependent effect.

  14. Association Between ACE Gene Polymorphism and QT Dispersion in Patients with Acute Myocardial Infarction.

    PubMed

    Karahan, Zulkuf; Ugurlu, Murat; Ucaman, Berzal; Veysel Ulug, Ali; Kaya, Ilyas; Cevik, Kemal; Sahin Adiyaman, Mehmet; Oztürk, Onder; Iyem, Hikmet; Ozdemir, Ferit

    2016-01-01

    Angiotensin converting enzyme (ACE) gene polymorphism is associated with high renin-angiotensin system causing myocardial fibrosis and ventricular repolarization abnormality. Based on these findings, this study was designed to determine the association between ACE gene insertion/deletion (I/D) polymorphism and QT dispersion after acute myocardial infarction (MI). The study included 108 patients with acute MI. Blood samples were obtained from all the patients for genomic DNA analysis. ECGs were recorded at baseline and at the end of a 6-month follow up. The OT dispersion was manually calculated. The mean age of the patients was 57.5 ±9.9 years (ranging from 36 to 70). The patients with DD genotype showed longer QT dispersion than patients with II or DI genotype at the baseline, while at the end of the six-month follow up the patients with DI genotype showed longer QT dispersion than patients with DD or II genotypes. However, the magnitude of the QT dispersion prolongation was higher in patients carrying the ACE D allele than patients who were not carrying it, at baseline and at the end of six-month follow up (52.5 ±2.6 msn vs. 47.5±2.1 msn at baseline, 57±3.2 msn vs. 53±2.6 msn in months, P: 0.428 and P: 0.613, respectively). Carriers of the D allele of ACE gene I/D polymorphism may be associated with QT dispersion prolongation in patients with MI.An interaction of QT dispersion and ACE gene polymorphism may be associated with an elevation of serum type I-C terminal pro-collagen concentration, possibly leading to myocardial fibrosis, and increased action potential duration.

  15. Association of MAOA and COMT gene polymorphisms with palatable food intake in children.

    PubMed

    Galvão, Ananda C S; Krüger, Raquel C; Campagnolo, Paula D B; Mattevi, Vanessa S; Vitolo, Márcia R; Almeida, Silvana

    2012-03-01

    Several studies have implicated dopamine (DA) in appetite regulation. The enzymes catechol-o-methyltransferase (COMT) and monoamine oxidase A (MAOA) control DA availability and their genes have well-characterized functional variants. In this study, we examined three polymorphisms in these genes, T941G and MAOAu-VNTR in the MAOA gene and Val158Met in the COMT gene, to investigate how heritable variations in enzymes that determine DA levels might influence food intake and nutritional status. This investigation was a cross-sectional examination of 354 Brazilian children of three to four years old. Polymorphisms were analyzed by PCR-based methods. Means of dietary and anthropometric data were compared among genotypes by one-way analyses of variance or Kruskal Wallis tests. The MAOAu-VNTR and COMT Val158Met polymorphisms were associated with the amount of palatable food intake in boys. Presence of the MAOAu-VNTR*long allele was associated with higher intake of lipid-dense foods (LDF) when compared with the *short allele (P=.009); the amount of sugar-dense foods (SDF) intake was also higher in males carriers of the MAOAu-VNTR *long allele than in carriers of the *short allele (P=.034). In the girls' sample, MAOAu-VNTR polymorphism was not associated with food intake and nutritional status. Carriers of the COMT Val158Met*Val allele presented higher intake of LDF when compared with Met/Met homozygotes (P=.008). This study provides the first indication that genetic variants of enzymes that control DA availability might be involved in determination of the amount of palatable food intake in children. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Polymorphisms of iodothyronine deiodinases (DIO1, DIO3) genes are not associated with recurrent depressive disorder.

    PubMed

    Gałecka, Elżbieta; Talarowska, Monika; Maes, Michael; Su, Kuan-Pin; Górski, Paweł; Szemraj, Janusz

    2016-10-01

    Depressive disorder is characterized by disturbances in the hypothalamic-pituitary-thyroid (HPT) axis and in the metabolism of thyroid hormones (TH). The evidence for changes in TH levels is observed in human sera and cerebrospinal fluid as well as in animal model studies. Iodothyronine deiodinases (DIOs) type 1, 2 and 3 (DIO1, DIO2, DIO3) are important enzymes for the synthesis and determination of TH concentration. This study aims to examine the link between recurrent depressive disorders (rDD) and two functionally known polymorphisms DIO1a-C/T (rs11206244) and DIO1b-A/G (rs12095080) within the DIO1 gene encoding DIO1 and two polymorphisms DIO3-C/T (rs17716499), DIO3-A/C (rs7150269) within the DIO3 gene encoding DIO3. Both variants were genotyped in 254 rDD patients and 197 healthy subjects using polymerase chain reaction. Basic methods and statistical analyses were used to estimate genetic variants in the risk of the disease. No significant associations were found between the polymorphisms examined here and rDD. There were no significant associations between genotypes distribution and demographic/medical variables. Odds ratios (ORdis) and corresponding 95% confidence interval (95% CI) were calculated, for example: for CC genotype of DIO1a C/T (ORdis=0.86, 95% CI: 0.59, 1.25). Functional variants within the DIO1 gene, which affect TH levels and polymorphisms in DIO3, are not confirmed to be associated with rDD. Nevertheless, considering previous data which indicate that the DIO1 gene is related to the depression, further studies on a larger sample size are recommended. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  17. Polymorphisms of the thiopurine S-methyltransferase gene among the Libyan population

    PubMed Central

    Zeglam, Hamza Ben; Benhamer, Abdrazak; Aboud, Adel; Rtemi, Haitem; Mattardi, Meftah; Saleh, Saleh Suleiman; Bashein, Abdullah; Enattah, Nabil

    2015-01-01

    Background Thiopurine S-methyltransferase (TPMT) is a cytosolic enzyme that catalyses the S-methylation of 6-mercaptopurine and azathioprine. Low activity phenotypes are correlated with polymorphism in the TPMT gene. Patients with low or undetectable TMPT activity could develop severe myelosuppression when they are treated with standard doses of thiopurine drugs. Since ethnic differences in the TPMT gene polymorphism have been demonstrated worldwide, assessing it in the Libyan population is worthwhile. Methods We investigated TPMT gene polymorphism in a total of 246 Libyan healthy adult blood donors from three different Libyan regions (Tripoli, Yefren, and Tawargha) and 50 children with acute lymphoblastic leukaemia (ALL). We used polymerase chain reaction restriction length polymorphism (PCR-RFLP) and allele-specific PCR-based assays to analyse the TPMT gene for the variants *2 c.238 G>C, *3A (c.460 G>A and c.719 A>G), *3B (c.460 G>A), and *3C (c.719 A>G). Results Our results show that the TPMT variants associated with low enzymatic activity were detected in 3.25% (8 in 246) of adult Libyan individuals and the frequency of total mutant alleles was 1.63%. Heterozygous genotypes were TPMT*3A in three subjects (0.61%) and TPMT*3C in five subjects (1.02%). No TPMT*2 and TPMT*3B allelic variants and no homozygous or compound heterozygous mutant alleles were detected. The normal allele (wild-type) was found in 98.4% of the adult individuals studied. No mutant alleles were detected among the 50 children who had ALL. Conclusions We report on the presence of the TPMT*3C and *3A mutant alleles in the Libyan population. Therefore, monitoring the patients to be treated with doses of thiopurine drugs for TPMT variants is worthwhile to avoid the development of severe myelosuppression. PMID:25819542

  18. Polymorphisms of the MMP-9 gene and abdominal aortic aneurysm

    PubMed Central

    Smallwood, Linda; Allcock, Richard; van Bockxmeer, Frank; Warrington, Nicole; Palmer, Lyle J; Iacopetta, Barry; Golledge, Jonathan; Norman, Paul E

    2008-01-01

    Background Increased matrix metalloproteinase-9 (MMP-9) activity has been implicated in the formation of abdominal aortic aneurysms (AAAs). The aim of the present study was to explore the association between potentially functional variants of the MMP-9 gene and AAA. Method The −1562C>T and −1811A>T variants of the MMP-9 gene were genotyped in 678 men with AAAs (>30mm in diameter) and 659 controls (aortic diameter 19−22mm) recruited from a population-based trial of screening for AAAs. The levels of MMP-9 were measured in a random subset of 300 cases and 84 controls. The association between genetic variants (including haplotypes) and AAA was assessed using multivariate logistic regression. Results There was no association between the MMP-9 −1562C>T (OR 0.70 95%CI 0.27, 1.82) or −1811A>T (OR 0.71, 95%CI 0.28, 1.85) genotypes, or the most common haplotype (OR 0.81 95%CI 0.62, 1.05), and AAA. The serum MMP-9 concentration (ng/mL) was higher in cases than controls and in minor allele carriers in cases and controls although the differences were not statistically significant. Conclusion The results suggest that a genetic tendency to have higher levels of circulating MMP-9 is not associated with AAAs. PMID:18763261

  19. Epistasis between neurochemical gene polymorphisms and risk for ADHD

    PubMed Central

    Segurado, Ricardo; Bellgrove, Mark A; Manconi, Francesca; Gill, Michael; Hawi, Ziarah

    2011-01-01

    A number of genes with function related to synaptic neurochemistry have been genetically associated with attention deficit/hyperactivity disorder. However, susceptibility to the development of common psychiatric disorders by single variants acting alone, can so far only explain a small proportion of the heritability of the phenotype. It has been postulated that the unexplained ‘dark heritability' may at least in part be due to epistatic effects, which may account for the small observed marginal associations, and the difficulties with replication of positive findings. We undertook a comprehensive exploration of pair-wise interactions between genetic variants in 24 candidate genic regions involved in monoaminergic catabolism, anabolism, release, re-uptake and signal transmission in a sample of 177 parent-affected child trios using a case-only design and a case–pseudocontrol design using conditional logistic regression. Marker-pairs thresholded on interaction odds ratio (OR) and P-value are presented. We detected a number of interaction ORs >4.0, including an interesting correlation between markers in the ADRA1B and DBH genes in affected individuals, and several further interesting but smaller effects. These effects are no larger than you would expect by chance under the assumption of independence of all pair-wise relations; however, independence is unlikely. Furthermore, the size of these effects is of interest and attempts to replicate these results in other samples are anticipated. PMID:21368917

  20. Phospholipid biosynthesis genes and susceptibility to obesity: analysis of expression and polymorphisms.

    PubMed

    Sharma, Neeraj K; Langberg, Kurt A; Mondal, Ashis K; Das, Swapan K

    2013-01-01

    Recent studies have identified links between phospholipid composition and altered cellular functions in animal models of obesity, but the involvement of phospholipid biosynthesis genes in human obesity are not well understood. We analyzed the transcript of four phospholipid biosynthesis genes in adipose and muscle from 170 subjects. We examined publicly available genome-wide association data from the GIANT and MAGIC cohorts to investigate the association of SNPs in these genes with obesity and glucose homeostasis traits, respectively. Trait-associated SNPs were genotyped to evaluate their roles in regulating expression in adipose. In adipose tissue, expression of PEMT, PCYT1A, and PTDSS2 were positively correlated and PCYT2 was negatively correlated with percent fat mass and body mass index (BMI). Among the polymorphisms in these genes, SNP rs4646404 in PEMT showed the strongest association (p = 3.07E-06) with waist-to-hip ratio (WHR) adjusted for BMI. The WHR-associated intronic SNP rs4646343 in the PEMT gene showed the strongest association with its expression in adipose. Allele "C" of this SNP was associated with higher WHR (p = 2.47E-05) and with higher expression (p = 4.10E-04). Our study shows that the expression of PEMT gene is high in obese insulin-resistant subjects. Intronic cis-regulatory polymorphisms may increase the genetic risk of obesity by modulating PEMT expression.

  1. Association between plasminogen activator inhibitor-1 4G/5G gene polymorphism and immunoglobulin A nephropathy susceptibility.

    PubMed

    Zhou, Tian-Biao; Jiang, Zong-Pei

    2015-02-01

    The association between plasminogen activator inhibitor-1 (PAI-1) 4 G/5 G gene polymorphism and immunoglobulin A nephropathy (IgAN) risk is still controversial. A meta-analysis was performed to evaluate the association between PAI-1 4 G/5 G gene polymorphism and IgAN susceptibility. A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic database. Four articles were identified for the analysis of association between PAI-1 4 G/5 G gene polymorphism and IgAN risk. 4 G allele was not associated with IgAN susceptibility in overall populations and in Asians. Furthermore, 4 G/4 G and 5 G/5 G genotype were not associated with IgAN for overall populations, Asians. In conclusion, PAI-1 4 G/5 G gene polymorphism was not associated with IgAN risk in overall populations and in Asians. However, more studies should be performed in the future.

  2. Association of maternal KIR gene content polymorphisms with reduction in perinatal transmission of HIV-1

    PubMed Central

    Omosun, Yusuf O.; Blackstock, Anna J.; Williamson, John; van Eijk, Anne Maria; Ayisi, John; Otieno, Juliana; Lal, Renu B.; ter Kuile, Feiko O.; Slutsker, Laurence

    2018-01-01

    The role of killer cell immunoglobulin-like receptors (KIRs) in the transmission of HIV-1 has not been extensively studied. Here, we investigated the association of KIR gene content polymorphisms with perinatal HIV-1 transmission. The KIR gene family comprising 16 genes was genotyped in 313 HIV-1 positive Kenyan mothers paired with their infants. Gene content polymorphisms were presented as presence of individual KIR genes, haplotypes, genotypes and KIR gene concordance. The genetic data were analyzed for associations with perinatal transmission of HIV. There was no association of infant KIR genes with perinatal HIV-1 transmission. After adjustment for gravidity, viral load, and CD4 cell count, there was evidence of an association between reduction in perinatal HIV-1 transmission and the maternal individual KIR genes KIR2DL2 (adjusted OR = 0.50; 95% CI: 0.24–1.02, P = 0.06), KIR2DL5 (adjusted OR = 0.47; 95% CI: 0.23–0.95, P = 0.04) and KIR2DS5 (adjusted OR = 0.39; 95% CI: 0.18–0.80, P = 0.01). Furthermore, these maternal KIR genes were only significantly associated with reduction in perinatal HIV transmission in women with CD4 cell count ≥ 350 cells/ μl and viral load <10000 copies/ml. Concordance analysis showed that when both mother and child had KIR2DS2, there was less likelihood of perinatal HIV-1 transmission (adjusted OR = 0.44; 95% CI: 0.20–0.96, P = 0.039). In conclusion, the maternal KIR genes KIR2DL2, KIR2DL5, KIR2DS5, and KIR2DS2 were associated with reduction of HIV-1 transmission from mother to child. Furthermore, maternal immune status is an important factor in the association of KIR with perinatal HIV transmission. PMID:29360870

  3. The TP53 gene polymorphisms and survival of sporadic breast cancer patients.

    PubMed

    Bišof, V; Salihović, M Peričić; Narančić, N Smolej; Skarić-Jurić, T; Jakić-Razumović, J; Janićijević, B; Rudan, P

    2012-06-01

    The TP53 gene polymorphisms, Arg72Pro and PIN3 (+16 bp), can have prognostic and predictive value in different cancers including breast cancer. The aim of the present study is to investigate a potential association between different genotypes of these polymorphisms and clinicopathological variables with survival of breast cancer patients in Croatian population. Ninety-four women with sporadic breast cancer were retrospectively analyzed. Median follow-up period was 67.9 months. The effects of basic clinical and histopathological characteristics of tumor on survival were tested by Cox's proportional hazards regression analysis. The TNM stage was associated with overall survival by Kaplan-Meier analysis, univariate, and multivariate Cox's proportional hazards regression analysis, while grade was associated with survival by Kaplan-Meier analysis and univariate Cox's proportional hazards regression analysis. Different genotypes of the Arg72Pro and PIN3 (+16 bp) polymorphisms had no significant impact on survival in breast cancer patients. However, in subgroup of patients treated with chemotherapy without anthracycline, the A2A2 genotype of the PIN3 (+16 bp) polymorphism was associated with poorer overall survival than other genotypes by Kaplan-Meier analysis (P = 0.048). The TP53 polymorphisms, Arg72Pro and PIN3 (+16 bp), had no impact on survival in unselected sporadic breast cancer patients in Croatian population. However, the results support the role of the A2A2 genotype of the PIN3 (+16 bp) polymorphism as a marker for identification of patients that may benefit from anthracycline-containing chemotherapy.

  4. Frequencies of VNTR and RFLP polymorphisms associated with factor VIII gene in Singapore

    SciTech Connect

    Fong, I.; Lai, P.S.; Ouah, T.C.

    1994-09-01

    The allelic frequency of any polymorphism within a population determines its usefulness for genetic counselling. This is important in populations of non-Caucasian origin as RFLPs may significantly differ among ethnic groups. We report a study of five intragenic polymorphisms in factor VIII gene carried out in Singapore. The three PCR-based RFLP markers studied were Intron 18/Bcl I, Intron 19/Hind III and Intron 22/Xba I. In an analysis of 148 unrelated normal X chromosomes, the allele frequencies were found to be A1 = 0.18, A2 = 0.82 (Bcl I RFLP), A1 = 0.80, A2 = 0.20 (Hind III RFLP) and A1more » = 0.58, and A2 = 0.42 (Xba I RFLP). The heterozygosity rates of 74 females analyzed separately were 31%, 32% and 84.2%, respectively. Linkage disequilibrium was also observed to some degree between Bcl I and Hind III polymorphism in our population. We have also analyzed a sequence polymorphism in Intron 7 using hybridization with radioactive-labelled {sup 32}P allele-specific oligonucleotide probes. This polymorphism was not very polymorphic in our population with only 2% of 117 individuals analyzed being informative. However, the use of a hypervariable dinucleotide repeat sequence (VNTR) in Intron 13 showed that 25 of our of 27 (93%) females were heterozygous. Allele frequencies ranged from 1 to 55 %. We conclude that a viable strategy for molecular analysis of Hemophilia A families in our population should include the use of Intron 18/Bcl I and Intron 22/Xba I RFLP markers and the Intron 13 VNTR marker.« less

  5. [Relationship of Ghrelin gene polymorphism with congenital anorectal malformation and Hirschsprung disease].

    PubMed

    Gao, Hong; Wang, Dajia; Zhao, Xiangxuan; Mi, Jie; Bai, Yuzuo; Wang, Weilin

    2015-07-01

    To explore the relationship of Ghrelin gene polymorphism with the occurrence of human anorectal malformations (ARMs) and Hirschsprung disease(HSCR). PCR and DNA sequencing were used to detect the single nucleotide polymorphism (SNPs) of 3 loci (rs139684563, rs149447194, rs186599567) genotype of Ghrelin gene in 100 children with ARMs, 100 children with HSCR, and 100 healthy children (normal group). Genovariation and gene mutation were analyzed with case-control method. Three loci SNPs were in accordance with Hardy-Weinberg genetic equilibrium. No significant differences were found in rs139684563 allele and genotype frequencies between the cases and the normal groups (P>0.05). The allele and genotype frequencies of rs149447194 and rs186599567 were significantly different between cases and normal group (P<0.05). DNA sequencing results showed that wild-type homozygous deletion (176th and 191th base A deletion, respectively) were found in rs149447194 and rs186599567of ARMs and HSCR children, and single base substitution was detected in rs149447194 of ARMs children (194th codon nucleotide CCT to CTC). The rs149447194 and the rs186599567 polymorphism changes may be associated with the pathogenesis of ARMs and HSCR.

  6. Polymorphic genetic variation in immune system genes: a study of two populations of Espirito Santo, Brazil.

    PubMed

    Dettogni, Raquel Spinassé; Sá, Ricardo Tristão; Tovar, Thaís Tristão; Louro, Iúri Drumond

    2013-08-01

    Mapping single nucleotide polymorphisms (SNPs) in genes potentially involved in immune responses may help understand the pathophysiology of infectious diseases in specific geographical regions. In this context, we have aimed to analyze the frequency of immunogenetic markers, focusing on genes CD209 (SNP -336A/G), FCγRIIa (SNP -131H/R), TNF-α (SNP -308A/G) and VDR (SNP Taq I) in two populations of the Espirito Santo State (ES), Brazil: general and Pomeranian populations. Peripheral blood genomic DNA was extracted from one hundred healthy individuals of the general population and from 59 Pomeranians. Polymorphic variant identification was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). SNP genotype frequencies were in Hardy-Weinberg Equilibrium. There was no statistically significant difference in allelic and genotypic distributions between the two populations studied. Statistically significant differences were observed for SNP genotype distribution in genes CD209, TNF-α and VDR when comparing the ES populations with other Brazilian populations. This is the first report of CD209, FcγRIIa, TNF-α and VDR allelic frequencies for the general and Pomeranian populations of ES.

  7. The role of xenobotic metabolism MGST1 gene polymorphism in colorectal cancer patients.

    PubMed

    Akil, Fardah; Akil, H A M; Lutfie, A M; Wibowo, Wahyu S; Miskad, Upik; Yusuf, Irawan

    2012-10-01

    to asses the role of Microsomal Glutathione S-Transferase1 (MGST1) gene as one of enzym metabolism that plays in enviromental factor. using case-control study, subjects with age less than 50 years were collected from teaching hospital Makassar between 2008-2010. Frozen or routinely processed tumour samples biopsy and peripheral blood were obtained from 35 CRC patients undergoing surgery and endoscopic examination with 61 subject as control. CRC cases were diagnosis by clinical examination and confirm by histopathology without familial aggregation of CRC. DNA resequencing was conducted for the 3 kb genomic DNA region MGST1 using PCR-restriction fragment length polymorphism (PCR-RFLP). from 96 subject, two varian single nucleotide polymorphisms (SNPs) 16454T>G and 16416G>A MGST1 were identified. Significant CRC association (p= 0.047) was detected in GG genotipe SNP 16454T>G MGST1 with 3.5 fold risk (95% confidence interval (CI) 0.962-13.191). the results suggest that MGST1 gene polymorphisms as one of environment gene may contribute to CRC risk in younger age (<50 years old).

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

    PubMed

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

    2006-11-01

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

  9. Association between HLA-E gene polymorphism and unexplained recurrent spontaneous abortion (RSA) in Iranian women.

    PubMed

    Fotoohi, Maryam; Ghasemi, Nasrin; Mirghanizadeh, Seyed Ali; Vakili, Mahmood; Samadi, Morteza

    2016-07-01

    Human leukocyte antigen-E (HLA-E)is a non-classical major histocompatibility complex (MHC) class I antigens which expressed on extra villous cytotrophoblast, which interacts with NKG2A, is an inhibitory receptor on natural killer (NK) cells and leading to down regulation of immune response in the maternal-fetal interface and provides maternal immune tolerance of the fetus. This study was designated to investigate the gene frequencies of E0101 and E0103 in HLA-E gene in Iranian women with recurrent spontaneous abortion (RSA). Amplification Refractory Mutation System (ARMS-PCR) technique was carried out to detect polymorphism in exon 3 of the HLA-E gene in women with RSA and controls (n=200). Differences between groups were analyzed by SPSS19 software using (2) test. There was no significant difference in the allele frequencies of the HLA-E polymorphism between RSA and fertile controls but HLA-E 0101/0103 heterozygous genotype was found to be significantly higher in RSA group (p=0.006, OR=1.73), so this genotype might confer susceptibility to RSA. Our results suggest that HLA-E 0101/0103 heterozygous genotype leads to increase of RSA risk. It seems that by genotyping of HLA-E polymorphism, we can predict the risk of RSA in infertile women.

  10. 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

  11. Association and family studies of DRD2 gene polymorphisms in alcohol dependence syndrome.

    PubMed

    Małecka, Iwona; Jasiewicz, Andrzej; Suchanecka, Aleksandra; Samochowiec, Jerzy; Grzywacz, Anna

    2014-11-06

    The human dopamine receptor 2 gene DRD2 plays a central role in susceptibility to Alcohol Dependence Syndrome (ADS). The aim of this study was to evaluate 3 single nucleotide polymorphisms: D2 (rs1076560), Tag1D (rs1800498), Tag1B (rs1079597) located in dopamine receptor 2 DRD2 gene and its role in alcohol dependence. DNA was provided from alcohol dependent (AD) patients (n=171) and healthy control subjects (n=160) all of Polish descent. The history of alcoholism was obtained using the Polish version of the SSAGA (Semi-Structured Assessment for the Genetics of Alcoholism). We conducted case-control association study and transmission disequilibrium test (TDT). Samples were genotyped using real-time PCR method. We did not confirm the association between studied polymorphisms and alcohol dependence syndrome. TDT reveled an adequate transmission of both alleles in the group of alcohol families. The lack of association of studied polymorphisms and ADS does not preclude its participation in the pathogenesis. Further research is needed to determine the actual contribution of DRD2 gene in the pathogenesis of alcoholism.

  12. Serotonin transporter gene polymorphism and psychiatric disorders: Is there a link?

    PubMed Central

    Margoob, Mushtaq A.; Mushtaq, Dhuha

    2011-01-01

    Though still in infancy, the field of psychiatric genetics holds great potential to contribute to the development of new diagnostic and therapeutic options to treat these disorders. Among a large number of existing neurotransmitter systems, the serotonin system dysfunction has been implicated in many psychiatric disorders and therapeutic efficacy of many drugs is also thought to be based on modulation of serotonin. Serotonin transporter gene polymorphism is one of the most extensively studied polymorphisms in psychiatric behavioral genetics. In this article, we review the status of evidence for association between the serotonin gene polymorphism and some common mental disorders like affective disorders, post-traumatic stress disorder, obsessive-compulsive disorder, suicide, autism, and other anxiety and personality disorders. Going beyond traditional association studies, gene-environment interaction, currently gaining momentum, is also discussed in the review. While the existing information of psychiatric genetics is inadequate for putting into practice genetic testing in the diagnostic work-up of the psychiatric patient, if consistent in future research attempts, such results can be of great help to improve the clinical care of a vast majority of patients suffering from such disorders. PMID:22303036

  13. Population-based case-control study of DRD2 gene polymorphisms and alcoholism.

    PubMed

    Bhaskar, L V K S; Thangaraj, K; Non, A L; Singh, Lalji; Rao, V R

    2010-10-01

    Several independent lines of evidence for genetic contributions to vulnerability to alcoholism exist. Dopamine is thought to play a major role in the mechanism of reward and reinforcement in response to alcohol. D2 dopamine receptor (DRD2) gene has been among the stronger candidate genes implicated in alcoholism. In this study, alcohol use was assessed in 196 randomly selected Kota individuals of Nilgiri Hills, South India. Six DRD2 SNPs were assessed in 81 individuals with alcoholism and 151 controls to evaluate the association between single nucleotide polymorphisms (SNPs) and alcoholism. Of the three models (dominant, recessive, and additive) tested for association between alcoholism and DRD2 SNPs, only the additive model shows association for three loci (rs1116313, TaqID, and rs2734835). Of six studied polymorphisms, five are in strong linkage disequilibrium forming onesingle haplotype block. Though the global haplotype analysis with these five SNPs was not significant, haplotype analysis using all six SNPs yielded a global P value of .033, even after adjusting for age. These findings support the importance of dopamine receptor gene polymorphisms in alcoholism. Further studies to replicate these findings in different populations are needed to confirm these results.

  14. 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.

  15. Polymorphism and methylation of the MC4R gene in obese and non-obese dogs.

    PubMed

    Mankowska, Monika; Nowacka-Woszuk, Joanna; Graczyk, Aneta; Ciazynska, Paulina; Stachowiak, Monika; Switonski, Marek

    2017-08-01

    The dog is considered to be a useful biomedical model for human diseases and disorders, including obesity. One of the numerous genes associated with human polygenic obesity is MC4R, encoding the melanocortin 4 receptor. The aim of our study was to analyze polymorphisms and methylation of the canine MC4R in relation to adiposity. Altogether 270 dogs representing four breeds predisposed to obesity: Labrador Retriever (n = 187), Golden Retriever (n = 38), Beagle (n = 28) and Cocker Spaniel (n = 17), were studied. The dogs were classified into three groups: lean, overweight and obese, according to the 5-point Body Condition Score (BCS) scale. In the cohort of Labradors a complete phenotypic data (age, sex, neutering status, body weight and BCS) were collected for 127 dogs. The entire coding sequence as well as 5' and 3'-flanking regions of the studied gene were sequenced and six polymorphic sites were reported. Genotype frequencies differed considerably between breeds and Labrador Retrievers appeared to be the less polymorphic. Moreover, distribution of some polymorphic variants differed significantly (P < 0.05) between small cohorts with diverse BCS in Golden Retrievers (c.777T>C, c.868C>T and c.*33C>G) and Beagles (c.-435T>C and c.637G>T). On the contrary, in Labradors no association between the studied polymorphisms and BCS or body weight was observed. Methylation analysis, using bisulfite DNA conversion followed by Sanger sequencing, was carried out for 12 dogs with BCS = 3 and 12 dogs with BCS = 5. Two intragenic CpG islands, containing 19 cytosines, were analyzed and the methylation profile did not differ significantly between lean and obese animals. We conclude that an association of the MC4R gene polymorphism with dog obesity or body weight is unlikely, in spite of the fact that some associations were found in small cohorts of Beagles and Golden Retrievers. Also methylation level of this gene is not related with dog adiposity.

  16. 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.

  17. Association of APOE gene polymorphism with lipid profile and coronary artery disease in Afro-Caribbeans

    PubMed Central

    Armand, Christophe; Bangou, Jacqueline; Blanchet-Deverly, Anne; Numeric, Patrick; Fonteau, Christiane; Michel, Carl-Thony; Ferdinand, Séverine; Bourrhis, Véronique; Vélayoudom-Céphise, Fritz-Line

    2017-01-01

    Objectives Apolipoprotein E gene (APOE) polymorphism is associated with the lipid profile and cardio-vascular disease. However, these relationships vary between ethnic groups. We evaluated, for the first time in an Afro-Caribbean population, the distribution of APOE polymorphisms and their associations with coronary artery disease (CAD), the lipid profile and other cardio-metabolic risk factors. Methods We studied 712 Afro-Caribbean subjects including 220 with documented CAD and 492 healthy subjects. TaqMan assays were performed to genotype rs7412 and rs429358, the two variants that determine the APOE alleles ε2, ε3 and ε4. The association between APOE genotype and the lipid profile was analysed by comparing ε2 carriers, ε3 homozygotes and ε4 carriers. Results The frequencies of ε2, ε3 and ε4 in the overall sample were 8%, 70% and 22%, respectively. CAD was not associated with APOE polymorphism. The total cholesterol level was higher in ε4 carriers compared with ε2 carriers: 5.07 vs 4.59 mmol/L (P = 0.016). The LDL-cholesterol level was lower in APOE ε2 carriers compared with ε3 homozygotes and ε4 carriers: 2.65 vs 3.03 and 3.17 mmol/L, respectively (p = 0.002). The total cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol ratios were similar in the three allelic groups. APOE polymorphism was not associated with diabetes, hypertension, waist circumference or body mass index. Conclusions Our results indicate that APOE gene polymorphism is associated with the lipid profile but not with CAD in Afro-Caribbean people. This lack of association with CAD may be explained by the low atherogenic profile observed in ε4 carriers, which may warrant further investigation. PMID:28727855

  18. Interleukin-4 Gene Intron 3 VNTR Polymorphism in Type 2 Diabetes Patients with Peripheral Neuropathy.

    PubMed

    Buraczynska, Monika; Buraczynska, Kinga; Zukowski, Pawel; Ksiazek, Andrzej

    2018-02-01

    Diabetic peripheral neuropathy (DPN) is one of late complications of diabetes mellitus. The aim of this study was to evaluate the association between variable number tandem repeat (VNTR) polymorphism in intron 3 of interleukin-4 gene and risk of DPN. We examined 926 T2DM patients and 420 healthy controls. In the patient group, 44% had DPN. Genomic DNA was isolated from all subjects and genotyped for the IL-4 VNTR polymorphism by polymerase chain reaction (PCR). No significant difference was observed in the frequency of minor P1 allele between T2DM patients and controls (OR 1.00, 95% CI 0.81-1.23, p = 0.988). The distribution of IL-4 VNTR polymorphism was compared between patients with DPN and those without it. The polymorphism was not significantly associated with DPN in studied subjects. In comparison of 406 T2DM patients with DPN and 520 patients without it, the OR (95% CI) for P1 allele was 0.82 (0.65-1.04), p = 0.10 and for P1P1 genotype 1.00 (0.53-1.89), p = 0.991. When two subgroups of patients with DPN, those with cardiovascular disease (CVD) and without CVD, were compared, subgroup with coexisting CVD had significantly higher frequency of P1 allele than patients without CVD, with odds ratio for the P1 allele 3.27 (95% CI 1.83-5.83), p = 0.0001. Our results demonstrated that VNTR polymorphism in the IL-4 gene is associated with DPN in type 2 diabetes patients with coexisting CVD.

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

    PubMed Central

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

    2015-01-01

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

  20. Serum paraoxonase-1 gene polymorphism and enzyme activity in patients with urolithiasis.

    PubMed

    Atar, Arda; Gedikbasi, Asuman; Sonmezay, Erkan; Kiraz, Zeynep Kusku; Abbasoglu, Semra; Tasci, Ali Ihsan; Tugcu, Volkan

    2016-01-01

    Paraoxonase-1 (PON1) is a high-density lipoprotein-associated enzyme implicated in the pathogenesis of atherosclerosis by protecting lipoproteins against peroxidation. PON1 has two genetic polymorphisms both due to amino acid substitution, one involving glutamine and arginine at position 192 and the other leucine and methionine at position 55. Recent reports suggest that nephrolithiasis and atherosclerosis share a number of risk factors. Our study aimed to compare the effects of PON1 192, PON1 55 polymorphisms, and PON1 activity in patients with urolithiasis and controls. PON1's arylesterase/paraoxonase activities and phenotype were determined in 158 stone forming cases (Group 1) and 138 non-stone forming controls (Group 2). The PON1 192 and PON1 55 polymorphisms were studied by polymerase chain reaction/restriction fragment length polymorphism. Paraoxonase activity was significantly lower in Group 1 than Group 2 (112 ± 31.8 vs. 208 ± 53.1 IU/L) (p < 0.001). The PON1 L55M polymorphism was significantly higher in Group 1. The "M" allele coding for PON1 was higher in Group 1 (p < 0.001). PON1 192 RR homozygotes had significantly higher PON1 activity than QR and QQ genotypes among all the patients (p < 0.001). The results of our study demonstrate that the PON1 55 gene "M" allele is associated with renal stone disease. Individuals possessing the "M" allele have a higher incidence of urolithiasis. The results of this study provide genetic evidence that the PON1 gene may play a role in stone formation. PON1 genotype determination may provide a tool to identify individuals who are at risk of urolithiasis.

  1. Gene-gene interactions of CYP2A6 and MAOA polymorphisms on smoking behavior in Chinese male population.

    PubMed

    Tang, Xun; Guo, Song; Sun, Hongqiang; Song, Xuemei; Jiang, Zuonin; Sheng, Lixiang; Zhou, Dongfeng; Hu, Yonghua; Chen, Dafang

    2009-05-01

    Nicotine is the major psychoactive ingredient in tobacco, and is responsible for dependence through the nicotine-stimulated reward pathway mediated by the central dopaminergic system. Consequently, genetic polymorphisms in both nicotine metabolism and dopamine catabolism genes may influence smoking behavior, and interact with each other resulting in risk modulation. In this study, we investigated the association and multilocus gene-gene interactions of cytochrome P450 2A6 (CYP2A6), dopamine beta-hydroxylase (DBH), catechol O-methyl transferase (COMT), and monoamine oxidase A (MAOA) polymorphisms with smoking behavior in a community-based Chinese male population. The polymorphisms were genotyped in 203 current smokers, 66 former smokers, and 102 never smokers. Multivariate logistic regression models and the multifactor dimensionality reduction method were used to analyze the association and multilocus gene-gene interactions. Statistically significant trends were shown for increased risk of smoking initiation in participants with CYP2A6*1B/CYP2A6*1B genotypes compared with those with CYP2A6*1A/CYP2A6*1A genotypes [odds ratio (OR)=3.5, 95% confidence interval (CI)= 1.5-8.1], and participants with CYP2A6*1/CYP2A6*1 genotypes were at higher risk of smoking initiation (OR=2.4, 95% CI=1.2-4.5) and smoking persistence (OR=4.0, 95% CI=1.5-10.3) than those who have CYP2A6*4C genotypes. Moreover, the best model involved a gene-gene interaction between MAOA and CYP2A6 was characterized by the multifactor dimensionality reduction method (64.11% accuracy, P<0.001), and indicated that carriers of the combined 1460 T/O genotype for MAOA EcoRV and CYP2A6*1/CYP2A6*1 genotypes were at higher risk of smoking (OR=15.4, 95% CI=4.5-52.5). These findings suggested a substantial influence of CYP2A6 polymorphism as well as the interaction with MAOA resulting in risk modulation on smoking behavior in Chinese male population.

  2. Associations of polymorphisms in the Pit-1 gene with growth and carcass traits in Angus beef cattle.

    PubMed

    Zhao, Q; Davis, M E; Hines, H C

    2004-08-01

    The Pit-1 gene was studied as a candidate for genetic markers of growth and carcass traits. Angus beef cattle that were divergently selected for high- or low-blood serum IGF-I concentration were used in this study. The single-strand conformation polymorphism method was used to identify polymorphism in the Pit-1 gene including regions from intron 2 to exon 6. Two polymorphisms, Pit1I3H (HinfI) and Pit1I3NL (NlaIII), were detected in intron 3 of the Pit-1 gene. One polymorphism, Pit1I4N (BstNI), was found in intron 4, and a single nucleotide polymorphism, Pit1I5, was found in intron 5. The previously reported polymorphism in exon 6, Pit1E6H (HinfI), was also studied in 416 Angus beef cattle. Associations of the polymorphisms with growth traits, carcass traits, and IGF-I concentration were analyzed using a general linear model procedure. No significant associations were observed between these polymorphisms and growth and carcass traits.

  3. Bactericidal/permeability increasing protein gene polymorphism and inflammatory bowel diseases: meta-analysis of five case-control studies.

    PubMed

    Fan, Lijuan; Fu, Guoning; Ding, Yuanyuan; Lv, Peng; Li, Hongyun

    2017-03-01

    Bactericidal/permeability increasing protein (BPI) gene polymorphisms have been extensively investigated in terms of their associations with inflammatory bowel disease (IBD), with contradictory results. The aim of this meta-analysis was to evaluate associations between BPI gene polymorphisms and the risk of IBD, Crohn's disease (CD), and ulcerative colitis (UC). Eligible studies from PubMed, Embase, and Cochrane library databases were identified. Ten studies (five CD and five UC) published in five papers were included in this meta-analysis. G645A polymorphism was associated with a decreased risk of UC in allele model, dominant model, and homozygous model. Our data suggested that BPI G645A polymorphism was associated with a decreased risk of UC; the BPI G645A polymorphism was not associated with the risk of CD.

  4. A polymorphism (rs1042522) in TP53 gene is a risk factor for Down Syndrome in Sicilian mothers.

    PubMed

    Salemi, Michele; Barone, Concetta; Salluzzo, Maria Grazia; Giambirtone, Mariaconcetta; Scillato, Francesco; Galati Rando, Rosanna; Romano, Carmelo; Morale, Maria Concetta; Ridolfo, Federico; Romano, Corrado

    2017-11-01

    Trisomy 21 is the most frequent genetic cause of intellectual disability. Tumor Protein 53 (TP53) gene down-regulation triggers chromosomal instability. A TP53 gene polymorphism c.215G > C (rs1042522) is associated with accumulation of aneuploid cells. We analyzed the TP53 c.215G > C (rs1042522) polymorphism in Sicilian mothers of subjects with Down Syndrome (DS) within a case-control study. Nucleotide polymorphism was detected by pyrosequencing technology. The distribution of TP53 c.215G > C polymorphism showed significant difference between mothers of subjects with DS and controls. Our data show that TP53 c.215G > C polymorphism is a risk factor for DS in Sicilian mothers.

  5. TGF-Beta Gene Polymorphisms in Food Allergic versus Non-Food Allergic Eosinophilic Esophagitis

    DTIC Science & Technology

    2012-10-01

    successful EoE therapy in 60-98% of subjects. Indeed, th e majority of children with EoE have specific IgE to foods but they often continue to ingest...sensitized children with EoE and the TGFb1 genes. W e hypothesize that in EoE there is a gene polymorphism (TGFb1) environment (food) interaction that...esophageal stricture form ation is an im portant complication of remodeling in EoE (6-12% of children ; 33% of adults), identif ying genetic polym orphisms in

  6. 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

    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.

  7. Passive smoking, Cyp1A1 gene polymorphism and dysmenorrhea

    PubMed Central

    Liu, Hong; Yang, Fan; Li, Zhiping; Chen, Changzhong; Fang, Zhian; Wang, Lihua; Hu, Yonghua; Chen, Dafang

    2007-01-01

    Objective This study investigated whether the association between passive smoking exposure and dysmenorrhea is modified by two susceptibility genes, CYP1A1MspI and CYP1A1HincII. Methods This report includes 1645 (1124 no dysmenorrhea, 521 dysmenorrhea) nonsmoking and nondrinking newly wed female workers at Anqing, China between June 1997 and June 2000. Multiple logistic regression models were used to estimate the associations of passive smoking exposure and genetic susceptibility with dysmenorrhea, adjusting for perceived stress. Results When stratified by women genotype, the adjusted OR of dysmenorrhea was 1.6 (95%CI=1.3-2.1) for passive smoking group with Ile/Ile462 genotype, and 1.5 (95%CI=1.1-2.1) with C/C6235 genotype, compared to non passive smoking group, respectively. The data further showed that there was a significant combined effect between passive smoking and the CYP1A1 Msp1 C/C6235 and HincII Ile/Ile462 genotype (OR=2.6, 95%CI=1.3-5.2). Conclusion CYP1A1 MspI and HincII genotypes modified the association between passive smoking and dysmenorrhea. PMID:17566695

  8. Prediction of exercise-mediated changes in metabolic markers by gene polymorphism.

    PubMed

    Kahara, Toshio; Takamura, Toshinari; Hayakawa, Tetsuo; Nagai, Yukihiro; Yamaguchi, Hiromi; Katsuki, Tatsuo; Katsuki, Ken-ichi; Katsuki, Michio; Kobayashi, Ken-ichi

    2002-08-01

    The effects of regular physical exercise on obesity-associated metabolic abnormalities vary for each individual. In this study, we investigated whether genotypes of genes associated with obesity can predict the effects of exercise on changes in metabolic markers in healthy men. Healthy Japanese men (n=106) performed the exercise program at 50% of their maximal heart rate for 20-60 min a day, 2-3 days each week for 3 months. The levels of fasting plasma glucose (FPG) and serum leptin significantly decreased after the exercise program. Polymorphisms of the beta3-adrenergic receptor (beta3AR) and uncoupling protein-1 (UCP-1) genes were analyzed with RFLP methods. In the Trp/Trp genotype of the beta3AR gene, the levels of serum leptin, FPG and fructosamine (FrAm) decreased significantly after the exercise program, but not in the Arg/Arg genotype. In the AG heterozygote and the GG homozygote of the UCP-1 gene, FPG and FrAm levels were significantly reduced, respectively. In conclusion, gene polymorphism of the beta3AR and UCP-1 was found to be associated with the exercise-mediated improvement in glucose tolerance and leptin resistance in healthy Japanese men.

  9. Novel polymorphisms of the APOA2 gene and its promoter region affect body traits in cattle.

    PubMed

    Zhou, Yang; Li, Caixia; Cai, Hanfang; Xu, Yao; Lan, Xianyong; Lei, Chuzhao; Chen, Hong

    2013-12-01

    Apolipoprotein A-II (APOA2) is one of the major constituents of high-density lipoprotein and plays a critical role in lipid metabolism and obesity. However, similar research for the bovine APOA2 gene is lacking. In this study, polymorphisms of the bovine APOA2 gene and its promoter region were detected in 1021 cows from four breeds by sequencing and PCR-RFLP methods. Totally, we detected six novel mutations which included one mutation in the promoter region, two mutations in the exons and three mutations in the introns. There were four polymorphisms within APOA2 gene were analyzed. The allele A, T, T and G frequencies of the four loci were predominant in the four breeds when in separate or combinations analysis which suggested cows with those alleles to be more adapted to the steppe environment. The association analysis indicated three SVs in Nangyang cows, two SVs in Qinchun cows and the 9 haplotypes in Nangyang cows were significantly associated with body traits (P<0.05 or P<0.01). The results of this study suggested the bovine APOA2 gene may be a strong candidate gene for body traits in the cattle breeding program. © 2013.

  10. The sheep growth hormone gene polymorphism and its effects on milk traits.

    PubMed

    Dettori, Maria Luisa; Pazzola, Michele; Pira, Emanuela; Paschino, Pietro; Vacca, Giuseppe Massimo

    2015-05-01

    Growth hormone (GH) is encoded by the GH gene, which may be single copy or duplicate in sheep. The two copies of the sheep GH gene (GH1/GH2-N and GH2-Z) were entirely sequenced in one 106 ewes of Sarda breed, in order to highlight sequence polymorphisms and investigate possible association between genetic variants and milk traits. Milk traits included milk yield, fat, protein, casein and lactose percentage. We evidenced 75 nucleotide changes. Transcription factor binding site prediction revealed two sequences potentially recognised by the pituitary-specific transcription factor POU1FI at the GH1/GH2-N gene, which were lost at the promoter of GH2-Z, which might explain the different tissues of expression of GH1/GH2-N (pituitary) and GH2-Z (placenta). Significant differences in milk traits were observed among genotypes at polymorphic loci only for the GH2-Z gene. Sheep with homozygote genotype ss748770547 CC had higher fat percentage (P < 0.01) than TT. SNP ss748770547 was part of a potential transcription factor binding site for C/EBP alpha (CCAAT/Enhancer Binding Protein), which is involved in the regulation of adipogenesis and adipoblast differentiation. SNP ss748770547, located in the GH2-Z gene 5' flanking region, may be a causal mutation affecting milk fat content. These findings might contribute to the knowledge of the sheep GH locus and might be useful in selection processes in sheep.

  11. Characterization of Heterobasidion occidentale transcriptomes reveals candidate genes and DNA polymorphisms for virulence variations.

    PubMed

    Liu, Jun-Jun; Shamoun, Simon Francis; Leal, Isabel; Kowbel, Robert; Sumampong, Grace; Zamany, Arezoo

    2018-05-01

    Characterization of genes involved in differentiation of pathogen species and isolates with variations of virulence traits provides valuable information to control tree diseases for meeting the challenges of sustainable forest health and phytosanitary trade issues. Lack of genetic knowledge and genomic resources hinders novel gene discovery, molecular mechanism studies and development of diagnostic tools in the management of forest pathogens. Here, we report on transcriptome profiling of Heterobasidion occidentale isolates with contrasting virulence levels. Comparative transcriptomic analysis identified orthologous groups exclusive to H. occidentale and its isolates, revealing biological processes involved in the differentiation of isolates. Further bioinformatics analyses identified an H. occidentale secretome, CYPome and other candidate effectors, from which genes with species- and isolate-specific expression were characterized. A large proportion of differentially expressed genes were revealed to have putative activities as cell wall modification enzymes and transcription factors, suggesting their potential roles in virulence and fungal pathogenesis. Next, large numbers of simple sequence repeats (SSRs) and single nucleotide polymorphisms (SNPs) were detected, including more than 14 000 interisolate non-synonymous SNPs. These polymorphic loci and species/isolate-specific genes may contribute to virulence variations and provide ideal DNA markers for development of diagnostic tools and investigation of genetic diversity. © 2018 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  12. Human population-specific gene expression and transcriptional network modification with polymorphic transposable elements

    PubMed Central

    Wang, Lu; Mariño-Ramírez, Leonardo

    2017-01-01

    Abstract Transposable element (TE) derived sequences are known to contribute to the regulation of the human genome. The majority of known TE-derived regulatory sequences correspond to relatively ancient insertions, which are fixed across human populations. The extent to which human genetic variation caused by recent TE activity leads to regulatory polymorphisms among populations has yet to be thoroughly explored. In this study, we searched for associations between polymorphic TE (polyTE) loci and human gene expression levels using an expression quantitative trait loci (eQTL) approach. We compared locus-specific polyTE insertion genotypes to B cell gene expression levels among 445 individuals from 5 human populations. Numerous human polyTE loci correspond to both cis and trans eQTL, and their regulatory effects are directly related to cell type-specific function in the immune system. PolyTE loci are associated with differences in expression between European and African population groups, and a single polyTE loci is indirectly associated with the expression of numerous genes via the regulation of the B cell-specific transcription factor PAX5. The polyTE-gene expression associations we found indicate that human TE genetic variation can have important phenotypic consequences. Our results reveal that TE-eQTL are involved in population-specific gene regulation as well as transcriptional network modification. PMID:27998931

  13. Screening for polymorphisms in the PXR gene in a Dutch population.

    PubMed

    Bosch, Tessa M; Deenen, Maarten; Pruntel, Roelof; Smits, Paul H M; Schellens, Jan H M; Beijnen, Jos H; Meijerman, Irma

    2006-05-01

    Cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of over 50% of all drugs currently in use. However, CYP3A4 expression shows a large inter-individual variation that cannot only be explained by genetic polymorphisms identified in this gene. The pregnane X receptor (PXR) has been identified as a transcriptional regulator of CYP3A4. Single nucleotide polymorphisms (SNPs) in the PXR gene could influence PXR activity and thereby CYP3A4 expression. This study was therefore aimed at determining the frequencies of known SNPs and detecting yet unknown SNPs in the PXR gene in a Dutch population. Genomic DNA was isolated from blood samples obtained from 100 healthy volunteers and subjected to PCR amplification, followed by DNA sequencing. The population, of which the ethnicity was 93% Caucasian, consisted of 79 female individuals and 21 males. A total of 24 SNPs were found in the PXR gene, eight of which are previously unknown. The allelic frequencies found in this population varied from 0.5 to 73%. Most of the previously detected SNPs were located in introns. One new SNP, T8555G in exon 8, causes an amino acid change of C379G and is located in the Ligand Binding Domain of PXR. Several SNPs were detected in the PXR gene, one of which is located in the ligand binding domain (LBD). These SNPs may influence PXR-mediated CYP3A4 induction.

  14. Association of VNTR polymorphisms in DRD4, 5-HTT and DAT1 genes with obesity.

    PubMed

    Uzun, Mustafa; Saglar, Emel; Kucukyildirim, Sibel; Erdem, Beril; Unlu, Hande; Mergen, Hatice

    2015-05-01

    To investigate the association between VNTR polymorphisms of DRD4, DAT1 and 5-HTT genes and obesity. Peripheral blood samples of 234 obese (BMI ≥ 30) and 148 healthy individuals (BMI ≤ 25) were objected to PCR to detect the VNTR of the 2nd intron of 5-HTT, 3rd exon of DRD4 and 3'UTR of DAT1 genes. The association between obesity and genotype distributions of 5-HTT, DAT1 and DRD4 genes and between obesity and distributions of allele frequencies were tested by Chi Square (χ(2)) test and were not found statistically significant. BMI values for genotype of obese and morbidly obese (BMI > 40) individuals were analyzed by Kruskal-Wallis and not found statistically significant differences between BMI values for the most frequent genotypes of 5-HTT, DAT1 and DRD4 genes. As a conclusion, there was no association between 5-HTT, DAT1 and DRD4 genes VNTR polymorphisms and obesity.

  15. Association Study of Serotonin Transporter Gene Polymorphisms with Obstructive Sleep Apnea Syndrome in Chinese Han Population

    PubMed Central

    Yue, Weihua; Liu, Huiguo; Zhang, Jishui; Zhang, Xianghui; Wang, Xiaoping; Liu, Tieqiao; Liu, Pozi; Hao, Wei

    2008-01-01

    Background: Since the serotonin (5-HT) is associated with circadian rhythm and breathing regulation, the serotonin transporter (5-HTT), which plays an important role in serotoninergic transmission, might be a strong candidate gene in the pathogenesis of obstructive sleep apnea syndrome (OSAS). Objective: To investigate the association of 5-HTT gene polymorphisms with OSAS and clinical characteristics. Methods: We genotyped the 5-HTT gene linked polymorphic region (5-HTTLPR) and a variable number of tandem repeats at intron 2 (STin2.VNTR) in 254 OSAS patients and 338 healthy controls in Chinese Han population. Results: In total sample, the 10-repeat allele of STin2.VNTR was significantly associated with OSAS (P = 0.007, OR = 1.72, 95% CI = 1.15~2.58), but no association was found in 5-HTTLPR. In male subjects, both polymorphisms showed significant association with OSAS (Allele L: P = 0.005, OR = 1.44, 95% CI = 1.11 to 1.87; Allele 10: P = 0.002, OR = 1.94, 95% CI = 1.26 to 3.00). Two haplotypes, S-12 and L-10, constructed by the above polymorphisms also revealed significant associations with OSAS (global P-values were 0.020 for total sample and 0.0006 for male subjects, respectively). Male patients carrying the haplotype S-12 showed a significantly lower apnea / hypopnea index (AHI), depressive factor, plasma 5-HT level and 5-hydroxyindolacetic acid (5-HIAA) levels, but higher episodic memory, when compared with non-S-12 carriers (P < 0.05). However, no significant differences were found in excessive daytime sleepiness or other psychological function across haplotype carriers (P > 0.05). Conclusions: These findings support that 5-HTT gene may be involved in susceptibility to OSAS, especially with sex-dependent effect. Citation: Yue W; Liu H; Zhang J; Zhang X; Wang X; Liu T; Liu P; Hao W. Association study of serotonin transporter gene polymorphisms with obstructive sleep apnea syndrome in chinese han population. SLEEP 2008;31(11):1535–1541. PMID:19014073

  16. Impact of vitamin D receptor gene polymorphisms in pathogenesis of Type-1 diabetes mellitus

    PubMed Central

    Kamel, Mahmoud M; Fouad, Shawky A; Salaheldin, Omina; El-Razek, Abd El-Rahman A Abd; El-Fatah, Abeer I Abd

    2014-01-01

    Background: Type 1 diabetes mellitus (TIDM) results from an immune-mediated destruction of insulin-producing-cells in the pancreatic islets of Langerhans. There are clear differences in immunogenetic predisposition to type1 diabetes among countries. Studies have indicated that vitamin D supplementation in early childhood decreases the risk of TIDM. Vitamin D exerts its action via the nuclear vitamin D receptor (VDR), which shows an extensive polymorphism. VDR gene polymorphisms have been associated with altered gene expression or gene function. Four single nucleotide polymorphisms (SNPs) in the VDR gene produce variation in four recognition sites. These recognition sites variants include Fok I, Bsm I, Apa I and Taq I. Aim of the study: TO investigate the relationship between VDR gene polymorphisms (at positions Taq I and Apa I) and the incidence of TIDM in Egyptian peoples. Subjects and methods: This study included 74 patients with type 1 DM in addition to 28 healthy age and sex matched control subjects. All of them were subjected to full history taking and clinical examination. Three ml of venous blood were withdrawn from each patient at fasting and postprandial times and used for genomic DNA extraction, estimation of Hb A1C, as well as, fasting and postprandial C-peptide and blood glucose levels. Results: Apa I recognition site was found in low frequency in diabetic patients (14/74) 18.9% while, its frequency was high (16/28) 57.1% among normal subjects. Taq I has two recognition sites. The first was found at nucleotide number 293 that was found in a frequency of (2/28) 7.1% in normal non-diabetic individuals while it was detected in (14/74) 18.9% in diabetic patients. The second Taq I recognition site was found at nucleotide number 494 without any differences between diabetic and normal individuals. Conclusion: This study indicates that there is an association between VDR genetic polymorphism and incidence of TIDM in Egyptian patients. PMID:25664062

  17. Association between TNFA Gene Polymorphisms and Helicobacter pylori Infection: A Meta-Analysis

    PubMed Central

    Sun, Xudong; Xu, Yuanyuan; Wang, Li; Zhang, Fuhua; Zhang, Jinhua; Fu, Ximei; Jing, Tao; Han, Jian

    2016-01-01

    Background Several host genetic factors are thought to affect susceptibility to Helicobacter pylori infection-related diseases, including tumor necrosis factor (TNF)-α. Previous studies have evaluated the association between TNFA gene polymorphisms and H. pylori infection, but the results were inconclusive. We conducted this meta-analysis to clarify the association between TNFA polymorphisms and H. pylori infection. Methods Published literature within PubMed, Embase, and the Cochrane Library were used in our meta-analysis. Data were analyzed with the Stata13.1 software package using pooled odds ratios (ORs) with 95% confidence intervals (CI). Results A total of 24 studies were included in our study. The TNFA -308G>A polymorphism was associated with decreasing H. pylori infection (AA vs. AG+GG, OR = 0.64, 95% CI = 0.43–0.97; AA vs. GG, OR = 0.64, 95% CI = 0.43–0.97). A significantly decreased risk was also found for -1031T>C polymorphism (CC vs. CT+TT, OR = 0.61, 95% CI = 0.44–0.84). -863C>A polymorphism was associated with increasing risk of H. pylori infection (AA+AC vs. CC, OR = 1.47, 95% CI = 1.16–1.86; A allele vs. C allele, OR = 1.40, 95% CI = 1.14–1.72). There was no significant association between -857C>T polymorphism and H. pylori infection. When stratified analysis was conducted on H. pylori infection detection methods, -857C>T and -863C>A polymorphisms were associated with H. pylori infection for the non-ELISA subgroup. When stratified for ethnicity or study design, -863C>A significantly increased the risk and -1031T>C decreased the risk for the Asian subgroup and hospital-based subgroup. Conclusion Results of our meta-analysis demonstrate that TNFA -308G>A and -1031 T>C polymorphisms may be protective factors against H. pylori infection, and -863C>A may be a risk factor, especially in Asian populations. Further studies with larger sample sizes are required to validate these results. PMID:26815578

  18. A meta-analysis evaluating the relationship between IL-18 gene promoter polymorphisms and an individual's susceptibility to HCV infection.

    PubMed

    Chen, W; Jing, M; Zhang, Q; Yuan, R; Jing, S

    2018-01-01

    Several observational studies have investigated interleukin-18 (IL-18) gene polymorphisms with regard to susceptibility to hepatitis C virus (HCV) infection, but the results have been inconsistent. To evaluate the relationships between functional polymorphisms in the IL-18 gene and an individual's susceptibility to HCV infection, a meta-analysis was performed. Methods: A literature search was conducted using the PubMed, EMBASE, Web of Science and China BioMedicine databases to investigate the correlation between IL-18 gene polymorphisms and susceptibility to HCV infection. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. The polymorphisms IL-18-607 C>A and -137 G>C were correlated with susceptibility to HCV infection in Asian populations. However, there was no evidence indicating a correlation between either of these polymorphisms and susceptibility to HCV infection in Caucasian populations. Our current meta-analysis suggests that the -607 C>A and -137 G>C polymorphisms in the IL-18 gene promoter play important roles in determining the response to HCV in Asian populations. More studies with larger sample sizes are needed to evaluate the associations between IL-18 genetic polymorphisms and HCV infection risk. © Acta Gastro-Enterologica Belgica.

  19. No evidence of association between NOD2/CARD15 gene polymorphism and atherosclerotic events after renal transplantation

    PubMed Central

    Courivaud, Cécile; Ferrand, Christophe; Deschamps, Marina; Tiberghien, Pierre; Chalopin, Jean-Marc; Duperrier, Anne; Saas, Philippe; Ducloux, Didier

    2006-01-01

    Stable renal transplant recipients (RTR) display high rates of atherosclerotic events (AE). Innate immunity and especially vascular inflammation play a role in the pathogenesis of atherosclerosis. It is illustrated both by an increased occurrence of post-renal transplant cardiovascular events in patients with elevated levels of C-reactive protein and by a correlation between post-transplant AE and Toll-like receptor-4 Asp299Gly polymorphism. Here, we analyze the influence NOD2/CARD15 gene polymorphism since NOD2 can modulate macrophage pro-inflammatory activity and macrophage is present in early atherosclerotic lesions. The incidence of single nucleotide polymorphism (SNP) in the three major polymorphic region of NOD2 gene (SNP8, SNP12 and SNP13) was assessed in 182 RTR and the correlation between such polymorphism and the development of AE was analyzed. No correlation was observed between NOD2 gene polymorphism and the occurrence of AE after renal transplantation. NOD2 gene polymorphism thus does not appear to influence cardiovascular complications in RTR. PMID:16641610

  20. CTLA-4 and IL-6 gene polymorphisms: Risk factors for recurrent pregnancy loss.

    PubMed

    Nasiri, Mahboobeh; Rasti, Zarnegar

    2016-12-01

    The purpose of the present study was to evaluate the possible association between CTLA-4 +49A/G and IL-6 -634C/G polymorphisms, and the risk of recurrent pregnancy loss (RPL). 240 women (120 healthy controls and 120 with RPL) were enrolled in this case-control study. Genotyping was performed using a PCR-RFLP technique. In the case of polymorphic CTLA-4 +49A/G, the wild type allele G was associated with a decreased risk of RPL (OR: 0.42, 95%CI: 0.25-0.69, p=0.001). As to IL-6 -634C/G polymorphism, a highly significant difference was observed, and those women who carry at least one mutant G allele presented a probability of developing RPL about 5 times greater than controls (OR: 5.1, 95%CI: 1.04-25.3, p=0.04). The results indicate that polymorphisms of CTLA-4 and IL-6 genes may influence the risk of developing RPL among Iranian women, suggesting that more research on the immunogenetics of pregnancy should be conducted to confirm our results, and to declare the exact roles of studied molecules in RPL pathogenesis. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  1. The association of ACE gene polymorphism with diabetic kidney disease and renoprotective efficacy of valsartan.

    PubMed

    Wang, Yuying; Peng, Wen; Zhang, Xiaoxue; Qiao, Huibo; Wang, Li; Xu, Zhigang; Wu, Chenguang

    2016-07-01

    To investigate the associations between the insertion/deletion (I/D) polymorphisms in the angiotensin converting enzyme (ACE) gene and susceptibility to diabetic kidney disease (DKD); and the efficacy of valsartan in reducing the urine protein in Type 2 diabetes mellitus (T2DM) patients. We enrolled 128 T2DM patients in this study, including 54 cases with DKD (DKD+) and 74 controls (DKD-). The ACE polymorphism was assayed by polymerase chain reaction (PCR), and the genotype distribution and allele frequency were analyzed. The DKD+ group was subdivided into the DD, ID and II subgroups, based on their genotypes. In addition, patients with DKD received valsartan treatment for 12 weeks. We determined changes in the urinary albumin to creatinine ratio (ACR) and serum creatinine (SCr). The frequencies of the genotypes DD and ID were higher in the DKD+ than in the DKD- group. The frequency of allele D was higher, and of allele I was lower, in the DKD+ than in DKD- group (p < 0.05). Following valsartan treatment, albuminuria was significantly decreased in subgroups DD and ID (p < 0.05). In T2DM patients, the ACE I/D polymorphism was associated with onset of DKD. Furthermore, the ACE I/D polymorphism influenced the renoprotective response to valsartan: Patients with the DD genotype benefitted the most from this treatment. © The Author(s) 2016.

  2. PICALM gene rs3851179 polymorphism contributes to Alzheimer's disease in an Asian population.

    PubMed

    Liu, Guiyou; Zhang, Shuyan; Cai, Zhiyou; Ma, Guoda; Zhang, Liangcai; Jiang, Yongshuai; Feng, Rennan; Liao, Mingzhi; Chen, Zugen; Zhao, Bin; Li, Keshen

    2013-06-01

    PICALM gene rs3851179 polymorphism was reported to an Alzheimer's disease (AD) susceptibility locus in a Caucasian population. However, recent studies reported consistent and inconsistent results in an Asian population. Four studies indicated no association between rs3851179 and AD in a Chinese population and one study reported weak association in a Japanese population. We consider that the failure to replicate the significant association between rs3851179 and AD may be caused by at least two reasons. The first reason may be the genetic heterogeneity in AD among different populations, and the second may be the relatively small sample size compared with large-scale GWAS in Caucasian ancestry. In order to confirm this view, in this research, we first evaluated the genetic heterogeneity of rs3851179 polymorphism in Caucasian and Asian populations. We then investigated rs3851179 polymorphism in an Asian population by a pooled analysis method and a meta-analysis method. We did not observe significant genetic heterogeneity of rs3851179 in the Caucasian and Asian populations. Our results indicate that rs3851179 polymorphism is significantly associated with AD in the Asian population by both pooled analysis and meta-analysis methods. We believe that our findings will be very useful for future genetic studies in AD.

  3. Glutathione S-transferase gene polymorphisms in celiac disease and their correlation with genomic instability phenotype.

    PubMed

    Fundia, Ariela F; Weich, Natalia; Crivelli, Adriana; La Motta, Graciela; Larripa, Irene B; Slavutsky, Irma

    2014-06-01

    Genomic instability and reduced glutathione S-transferase (GST) activity have been identified as potential risk factors for malignant complications in celiac disease (CD). In this study, we assessed the possible influence of GST polymorphisms on genome instability phenotypes in a genetically characterised group of celiac patients from previous studies. The deletion polymorphisms in GSTM1 and GSTT1 genes and the single-nucleotide polymorphism GSTP1 c.313A>G were genotyped using PCR in a set of 20 untreated adult patients with a known genomic instability phenotype and 69 age- and sex-matched healthy individuals. The frequencies of variant genotypes in patients were GSTM1-null (30%), GSTT1-null (5%), GSTP1-AG (60%) and GSTP1-GG (15%), and they showed no differences from controls. No significant differences were found in the genotype distribution based on telomere length. Cases with GSTM1-null genotype (83%) and microsatellite stability were more frequent than those with genomic instability. Moreover, carriers of GSTP1-variant genotype (73%) and stable phenotype were significantly increased compared to unstable patients (27%) (P=0.031). No differences were found according to the clinical-pathological characteristics of celiac cases. No association between GST polymorphic variants and celiac-associated genomic instability was proven in our cohort. Future studies should explore the usefulness of other biomarkers to distinguish celiac patients who are susceptible to cancer development. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  4. Vitamin C transporter gene polymorphisms, dietary vitamin C and serum ascorbic acid.

    PubMed

    Cahill, Leah E; El-Sohemy, Ahmed

    2009-01-01

    Vitamin C transporter proteins SVCT1 and SVCT2 are required for the absorption and transport of vitamin C in humans. This study aims to determine whether common SVCT genotypes modify the association between dietary vitamin C and serum ascorbic acid. Non-smoking men and women (n=1,046) aged 20-29 were participants of the Toronto Nutrigenomics and Health Study. Overnight fasting blood samples were collected to determine serum ascorbic acid concentrations by HPLC and to genotype for two SVCT1 (rs4257763 and rs6596473) and two SVCT2 (rs6139591 and rs2681116) polymorphisms. No diet-gene interactions were observed for the vitamin C transporter polymorphisms, however, the average (mean+/-SE) serum ascorbic acid concentrations differed between rs4257763 genotypes (GG: 24.4+/-1.3, GA: 26.8+/-1.1, AA: 29.7+/-1.4 micromol/l; p=0.002). For this polymorphism, the correlation between dietary vitamin C and serum ascorbic acid was only significant in subjects with a G allele. The SVCT2 polymorphisms also appeared to modify the strength of the diet-serum correlation. Our findings demonstrate that genetic variation in SVCT1 can influence serum ascorbic acid concentrations and that SVCT1 and SVCT2 genotypes modify the strength of the correlation between dietary vitamin C and serum ascorbic acid. Copyright © 2010 S. Karger AG, Basel.

  5. Polymorphisms in the oxytocin receptor gene are associated with the development of psychopathy.

    PubMed

    Dadds, Mark R; Moul, Caroline; Cauchi, Avril; Dobson-Stone, Carol; Hawes, David J; Brennan, John; Urwin, Ruth; Ebstein, Richard E

    2014-02-01

    The co-occurrence of child conduct problems (CPs) and callous-unemotional (CU) traits confers risk for psychopathy. The oxytocin (OXT) system is a likely candidate for involvement in the development of psychopathy. We tested variations in the OXT receptor gene (OXTR) in CP children and adolescents with varying levels of CU traits. Two samples of Caucasian children, aged 4-16 years, who met DSM criteria for disruptive behavior problems and had no features of autism spectrum disorder, were stratified into low versus high CU traits. Measures were the frequencies of nine candidate OXTR polymorphisms (single nucleotide polymorphisms). In Sample 1, high CU traits were associated with single nucleotide polymorphism rs1042778 in the 3' untranslated region of OXTR and the CGCT haplotype of rs2268490, rs2254298, rs237889, and rs13316193. The association of rs1042778 was replicated in the second rural sample and held across gender and child versus adolescent age groups. We conclude that polymorphic variation of the OXTR characterizes children with high levels of CU traits and CPs. The results are consistent with a hypothesized role of OXT in the developmental antecedents of psychopathy, particularly the differential amygdala activation model of psychopathic traits, and add genetic evidence that high CU traits specify a distinct subgroup within CP children.

  6. Vitamin D receptor gene polymorphisms and musculoskeletal injuries in professional football players

    PubMed Central

    MASSIDDA, MYOSOTIS; CORRIAS, LAURA; BACHIS, VALERIA; CUGIA, PAOLO; PIRAS, FRANCESCO; SCORCU, MARCO; CALÒ, CARLA M.

    2015-01-01

    The aim of the present study was to investigate the association between vitamin D receptor (VDR) gene polymorphisms and musculoskeletal injury (MI) in elite football players. In total, 54 male professional football players were recruited from an official Italian professional championship team between 2009 and 2013. The cohort was genotyped for the ApaI, BsmI and FokI polymorphisms and MI data were collected over four football seasons. No significant differences were identified among the genotypes in the incidence rates or severity of MI (P=0.254). In addition, no significant associations were observed between VDR polymorphisms and MI phenotypes (P=0.460). However, the results of the casewise multiple regression analysis indicated that the ApaI genotypes accounted for 18% of injury severity (P=0.002). Therefore, while the BsmI and FokI polymorphisms did not appear to be associated with the severity or incidence of MI, the ApaI genotypes may have influenced the severity of muscle injury in top-level football players. PMID:26161149

  7. Synaptosomal-associated protein 25 gene polymorphisms and antisocial personality disorder: association with temperament and psychopathy.

    PubMed

    Basoglu, Cengiz; Oner, Ozgur; Ates, Alpay; Algul, Ayhan; Bez, Yasin; Cetin, Mesut; Herken, Hasan; Erdal, Mehmet Emin; Munir, Kerim M

    2011-06-01

    The molecular genetic of personality disorders has been investigated in several studies; however, the association of antisocial behaviours with synaptosomal-associated protein 25 (SNAP25) gene polymorphisms has not. This association is of interest as SNAP25 gene polymorphism has been associated with attention-deficit hyperactivity disorder and personality. We compared the distribution of DdeI and MnII polymorphisms in 91 young male offenders and in 38 sex-matched healthy control subjects. We also investigated the association of SNAP25 gene polymorphisms with severity of psychopathy and with temperament traits: novelty seeking, harm avoidance, and reward dependence. The MnII T/T and DdeI T/T genotypes were more frequently present in male subjects with antisocial personality disorder (APD) than in sex-matched healthy control subjects. The association was stronger when the frequency of both DdeI and MnII T/T were taken into account. In the APD group, the genotype was not significantly associated with the Psychopathy Checklist-Revised scores, measuring the severity of psychopathy. However, the APD subjects with the MnII T/T genotype had higher novelty seeking scores; whereas, subjects with the DdeI T/T genotype had lower reward dependence scores. Again, the association between genotype and novelty seeking was stronger when both DdeI and MnII genotypes were taken into account. DdeI and MnII T/T genotypes may be a risk factor for antisocial behaviours. The association of the SNAP25 DdeI T/T and MnII T/T genotypes with lower reward dependence and higher novelty seeking suggested that SNAP25 genotype might influence other personality disorders, as well.

  8. Synaptosomal-Associated Protein 25 Gene Polymorphisms and Antisocial Personality Disorder: Association With Temperament and Psychopathy

    PubMed Central

    Basoglu, Cengiz; Oner, Ozgur; Ates, Alpay; Algul, Ayhan; Bez, Yasin; Cetin, Mesut; Herken, Hasan; Erdal, Mehmet Emin; Munir, Kerim M

    2011-01-01

    Objective The molecular genetic of personality disorders has been investigated in several studies; however, the association of antisocial behaviours with synaptosomal-associated protein 25 (SNAP25) gene polymorphisms has not. This association is of interest as SNAP25 gene polymorphism has been associated with attention-deficit hyperactivity disorder and personality. Methods We compared the distribution of DdeI and MnlI polymorphisms in 91 young male offenders and in 38 sex-matched healthy control subjects. We also investigated the association of SNAP25 gene polymorphisms with severity of psychopathy and with temperament traits: novelty seeking, harm avoidance, and reward dependence. Results The MnlI T/T and DdeI T/T genotypes were more frequently present in male subjects with antisocial personality disorder (APD) than in sex-matched healthy control subjects. The association was stronger when the frequency of both DdeI and MnlI T/T were taken into account. In the APD group, the genotype was not significantly associated with the Psychopathy Checklist–Revised scores, measuring the severity of psychopathy. However, the APD subjects with the MnlI T/T genotype had higher novelty seeking scores; whereas, subjects with the DdeI T/T genotype had lower reward dependence scores. Again, the association between genotype and novelty seeking was stronger when both DdeI and MnlI genotypes were taken into account. Conclusion DdeI and MnlI T/T genotypes may be a risk factor for antisocial behaviours. The association of the SNAP25 DdeI T/T and MnlI T/T genotypes with lower reward dependence and higher novelty seeking suggested that SNAP25 genotype might influence other personality disorders, as well. PMID:21756448

  9. Polymorphisms within the canine MLPH gene are associated with dilute coat color in dogs

    PubMed Central

    Philipp, Ute; Hamann, Henning; Mecklenburg, Lars; Nishino, Seiji; Mignot, Emmanuel; Günzel-Apel, Anne-Rose; Schmutz, Sheila M; Leeb, Tosso

    2005-01-01

    Background Pinschers and other dogs with coat color dilution show a characteristic pigmentation phenotype. The fur colors are a lighter shade, e.g. silvery grey (blue) instead of black and a sandy color (Isabella fawn) instead of red or brown. In some dogs the coat color dilution is sometimes accompanied by hair loss and recurrent skin inflammation, the so called color dilution alopecia (CDA) or black hair follicular dysplasia (BHFD). In humans and mice a comparable pigmentation phenotype without any documented hair loss is caused by mutations within the melanophilin gene (MLPH). Results We sequenced the canine MLPH gene and performed a mutation analysis of the MLPH exons in 6 Doberman Pinschers and 5 German Pinschers. A total of 48 sequence variations was identified within and between the breeds. Three families of dogs showed co-segregation for at least one polymorphism in an MLPH exon and the dilute phenotype. No single polymorphism was identified in the coding sequences or at splice sites that is likely to be causative for the dilute phenotype of all dogs examined. In 18 German Pinschers a mutation in exon 7 (R199H) was consistently associated with the dilute phenotype. However, as this mutation was present in homozygous state in four dogs of other breeds with wildtype pigmentation, it seems unlikely that this mutation is truly causative for coat color dilution. In Doberman Pinschers as well as in Large Munsterlanders with BHFD, a set of single nucleotide polymorphisms (SNPs) around exon 2 was identified that show a highly significant association to the dilute phenotype. Conclusion This study provides evidence that coat color dilution is caused by one or more mutations within or near the MLPH gene in several dog breeds. The data on polymorphisms that are strongly associated with the dilute phenotype will allow the genetic testing of Pinschers to facilitate the breeding of dogs with defined coat colors and to select against Large Munsterlanders carrying BHFD

  10. Polymorphisms within the canine MLPH gene are associated with dilute coat color in dogs.

    PubMed

    Philipp, Ute; Hamann, Henning; Mecklenburg, Lars; Nishino, Seiji; Mignot, Emmanuel; Günzel-Apel, Anne-Rose; Schmutz, Sheila M; Leeb, Tosso

    2005-06-16

    Pinschers and other dogs with coat color dilution show a characteristic pigmentation phenotype. The fur colors are a lighter shade, e.g. silvery grey (blue) instead of black and a sandy color (Isabella fawn) instead of red or brown. In some dogs the coat color dilution is sometimes accompanied by hair loss and recurrent skin inflammation, the so called color dilution alopecia (CDA) or black hair follicular dysplasia (BHFD). In humans and mice a comparable pigmentation phenotype without any documented hair loss is caused by mutations within the melanophilin gene (MLPH). We sequenced the canine MLPH gene and performed a mutation analysis of the MLPH exons in 6 Doberman Pinschers and 5 German Pinschers. A total of 48 sequence variations was identified within and between the breeds. Three families of dogs showed co-segregation for at least one polymorphism in an MLPH exon and the dilute phenotype. No single polymorphism was identified in the coding sequences or at splice sites that is likely to be causative for the dilute phenotype of all dogs examined. In 18 German Pinschers a mutation in exon 7 (R199H) was consistently associated with the dilute phenotype. However, as this mutation was present in homozygous state in four dogs of other breeds with wildtype pigmentation, it seems unlikely that this mutation is truly causative for coat color dilution. In Doberman Pinschers as well as in Large Munsterlanders with BHFD, a set of single nucleotide polymorphisms (SNPs) around exon 2 was identified that show a highly significant association to the dilute phenotype. This study provides evidence that coat color dilution is caused by one or more mutations within or near the MLPH gene in several dog breeds. The data on polymorphisms that are strongly associated with the dilute phenotype will allow the genetic testing of Pinschers to facilitate the breeding of dogs with defined coat colors and to select against Large Munsterlanders carrying BHFD.

  11. Inflammatory gene polymorphisms and risk of postoperative myocardial infarction after cardiac surgery.

    PubMed

    Podgoreanu, M V; White, W D; Morris, R W; Mathew, J P; Stafford-Smith, M; Welsby, I J; Grocott, H P; Milano, C A; Newman, M F; Schwinn, D A

    2006-07-04

    The inflammatory response triggered by cardiac surgery with cardiopulmonary bypass (CPB) is a primary mechanism in the pathogenesis of postoperative myocardial infarction (PMI), a multifactorial disorder with significant inter-patient variability poorly predicted by clinical and procedural factors. We tested the hypothesis that candidate gene polymorphisms in inflammatory pathways contribute to risk of PMI after cardiac surgery. We genotyped 48 polymorphisms from 23 candidate genes in a prospective cohort of 434 patients undergoing elective cardiac surgery with CPB. PMI was defined as creatine kinase-MB isoenzyme level > or = 10x upper limit of normal at 24 hours postoperatively. A 2-step analysis strategy was used: marker selection, followed by model building. To minimize false-positive associations, we adjusted for multiple testing by permutation analysis, Bonferroni correction, and controlling the false discovery rate; 52 patients (12%) experienced PMI. After adjusting for multiple comparisons and clinical risk factors, 3 polymorphisms were found to be independent predictors of PMI (adjusted P<0.05; false discovery rate <10%). These gene variants encode the proinflammatory cytokine interleukin 6 (IL6 -572G>C; odds ratio [OR], 2.47), and 2 adhesion molecules: intercellular adhesion molecule-1 (ICAM1 Lys469Glu; OR, 1.88), and E-selectin (SELE 98G>T; OR, 0.16). The inclusion of genotypic information from these polymorphisms improved prediction models for PMI based on traditional risk factors alone (C-statistic 0.764 versus 0.703). Functional genetic variants in cytokine and leukocyte-endothelial interaction pathways are independently associated with severity of myonecrosis after cardiac surgery. This may aid in preoperative identification of high-risk cardiac surgical patients and development of novel cardioprotective strategies.

  12. Effects of energy expenditure gene polymorphisms on obesity-related traits in obese children.

    PubMed

    Csernus, Katalin; Pauler, Gábor; Erhardt, Éva; Lányi, Éva; Molnár, Dénes

    2015-01-01

    To assess the frequencies of common polymorphisms of genes associated with energy expenditure among Hungarian obese children and investigate their influences on obesity-related traits and metabolic complications of common childhood obesity. In a total of 528 obese children (age 13.2±2.6 years) an oral glucose tolerance test and determination of fasting serum lipid levels were carried out, blood pressure and resting energy expenditure were measured and the children were genotyped for the following gene polymorphisms: Trp64Arg of β3-adrenoreceptor (ADRB3), -3826 A/G of uncoupling protein (UCP)-1, exon 8 45 bp del/ins and -866 G/A of UCP-2, -55 C/T of UCP-3, and Pro12Ala of peroxisome-proliferator activated receptor gamma-2. Carriers of the ADRB3 Arg64 allele had a significantly higher relative body weight and relative body mass index compared with non-carriers. The UCP-2 exon 8 del/ins polymorphism was associated with higher degree of obesity, insulin resistance, dyslipideamia and lower adjusted metabolic rate. Children with UCP-3 -55 T/T genotype had a significantly lower adjusted metabolic rate than the C allele carriers. We found evidence for associations between common polymorphisms of the ADRB3, the UCP-2 and UCP-3 genes and basic metabolic rate as well as level and metabolic consequences of common obesity among Hungarian school-aged children. Copyright © 2014 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  13. Association between Single Nucleotide Polymorphism of Vitamin D Receptor Gene FokI Polymorphism and Clinical Progress of Benign Prostatic Hyperplasia

    PubMed Central

    Ruan, Li; Zhu, Jian-guo; Pan, Cong; Hua, Xing; Yuan, Dong-bo; Li, Zheng-ming; Zhong, Wei-de

    2015-01-01

    Background. The aim of the study was to investigate the association between single nucleotide polymorphism (SNP) of vitamin D receptor (VDR) gene and clinical progress of benign prostatic hyperplasia (BPH) in Chinese men. Methods. The DNA was extracted from blood of 200 BPH patients with operation (progression group) and 200 patients without operation (control group), respectively. The genotypes of VDR gene FokI SNP represented by “F/f” were identified by PCR-restriction fragment length polymorphism. The odds ratio (OR) of having progression of BPH for having the genotype were calculated. Results. Our date indicated that the f alleles of the VDR gene FokI SNP associated with the progression of BPH (P = 0.009). Conclusion. For the first time, our study demonstrated that VDR gene FokI SNP may be associated with the risk of BPH progress. PMID:25685834

  14. CD44 Gene Polymorphisms in Breast Cancer Risk and Prognosis: A Study in North Indian Population

    PubMed Central

    Tulsyan, Sonam; Agarwal, Gaurav; Lal, Punita; Agrawal, Sushma; Mittal, Rama Devi; Mittal, Balraj

    2013-01-01

    Background Cell surface biomarker CD44 plays an important role in breast cancer cell growth, differentiation, invasion, angiogenesis and tumour metastasis. Therefore, we aimed to investigate the role of CD44 gene polymorphisms in breast cancer risk and prognosis in North Indian population. Materials & Methods A total of 258 breast cancer patients and 241 healthy controls were included in the case-control study for risk prediction. According to RECIST, 114 patients who received neo-adjuvant chemotherapy were recruited for the evaluation of breast cancer prognosis. We examined the association of tagging SNP (rs353639) of Hapmap Gujrati Indians in Houston (GIH population) in CD44 gene along with a significant reported SNP (rs13347) in Chinese population by genotyping using Taqman allelic discrimination assays. Statistical analysis was done using SPSS software, version 17. In-silico analysis for prediction of functional effects was done using F-SNP and FAST-SNP. Results No significant association of both the genetic variants of the CD44 gene polymorphisms was found with breast cancer risk. On performing univariate analysis with clinicopathological characteristics and treatment response, we found significant association of genotype (CT+TT) of rs13347 polymorphism with earlier age of onset (P = 0.029, OR = 0.037). However, significance was lost in multivariate analysis. For rs353639 polymorphism, significant association was seen with clinical tumour size, both at the genotypic (AC+CC) (P = 0.039, OR = 3.02) as well as the allelic (C) (P = 0.042, OR = 2.87) levels. On performing multivariate analysis, increased significance of variant genotype (P = 0.017, OR = 4.29) and allele (P = 0.025, OR = 3.34) of rs353639 was found with clinical tumour size. In-silico analysis using F-SNP, showed altered transcriptional regulation for rs353639 polymorphism. Conclusions These findings suggest that CD44 rs353639 genetic variants may have

  15. Association between FOXO3A gene polymorphisms and human longevity: a meta-analysis

    PubMed Central

    Bao, Ji-Ming; Song, Xian-Lu; Hong, Ying-Qia; Zhu, Hai-Li; Li, Cui; Zhang, Tao; Chen, Wei; Zhao, Shan-Chao; Chen, Qing

    2014-01-01

    Numerous studies have shown associations between the FOXO3A gene, encoding the forkhead box O3 transcription factor, and human or specifically male longevity. However, the associations of specific FOXO3A polymorphisms with longevity remain inconclusive. We performed a meta-analysis of existing studies to clarify these potential associations. A comprehensive search was conducted to identify studies of FOXO3A gene polymorphisms and longevity. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by comparing the minor and major alleles. A total of seven articles reporting associations of FOXO3A polymorphisms with longevity were identified and included in this meta-analysis. These comprised 11 independent studies with 5241 cases and 5724 controls from different ethnic groups. rs2802292, rs2764264, rs13217795, rs1935949 and rs2802288 polymorphisms were associated with human longevity (OR = 1.36, 95% CI = 1.10–1.69, P = 0.005; OR = 1.20, 95% CI = 1.04–1.37, P = 0.01; OR = 1.27, 95% CI = 1.10–1.46, P = 0.001; OR = 1.14, 95% CI = 1.01–1.27 and OR = 1.24, 95% CI = 1.07–1.43, P = 0.003, respectively). Analysis stratified by gender indicated significant associations between rs2802292, rs2764264 and rs13217795 and male longevity (OR = 1.54, 95% CI = 1.33–1.79, P < 0.001; OR = 1.38, 95% CI = 1.15–1.66, P = 0.001; and OR = 1.39, 95% CI = 1.15–1.67, P = 0.001), but rs2802292, rs2764264 and rs1935949 were not linked to female longevity. Moreover, our study showed no association between rs2153960, rs7762395 or rs13220810 polymorphisms and longevity. In conclusion, this meta-analysis indicates a significant association of five FOXO3A gene polymorphisms with longevity, with the effects of rs2802292 and rs2764264 being male-specific. Further investigations are required to confirm these findings. PMID:24589462

  16. AB126. Association between FOX03A gene polymorphisms and human longevity: a meta-analysis

    PubMed Central

    Zhao, Shanchao; Bao, Jiming; Song, Xianlu

    2016-01-01

    Objective Numerous studies have shown associations between the FOX03A gene, encoding the forkhead box 03 transcription factor, and human or specifically male longevity. However, the associations of specific FOX03A polymorphisms with longevity remain inconclusive. We performed a meta-analysis of existing studies to clarify these potential associations. Methods A comprehensive search was conducted to identify studies of FOX03A gene polymorphisms and longevity. Pooled odds ratios (ORs) and 95% confidence intervals (Cls) were calculated by comparing the minor and major alleles. Results A total of seven articles reporting associations of FOX03A polymorphisms with longevity were identified and included in this meta-analysis. These comprised 11 independent studies with 5241 cases and 5724 controls from different ethnic groups. rs2802292, rs2764264, rsI3217795, rs1935949 and rs2802288 polymorphisms were associated with human longevity (OR =1.36, 95% CI, 1. 10–1.69, P=0.005; OR =1.20, 95% CI, 1.04–1.37, P=0.01; OR =1.27, 95% CI, 1.10–1.46, P=0.001; OR =1.14, 95% CI, 1.01–1.27 and OR =1.24, 95% CI, 1.07–1.43, P=0.003, respectively). Analysis is stratified by gender indicated significant associations between rs2802292, rs2764264 and rs13217795 and male longevity (OR =1.54, 95% CI, 1.33–1.79, P<0.001; OR =1.38, 95% CI, 1.15–1.66, P=0.001; and OR =1.39, 95% CI, 1.15–1.67, P=0.001), but rs2802292, rs2764264 and rs1935949 were not linked to female longevity. Moreover, our study showed no association between rs2153960, rs7762395 or rs13220810 polymorphisms and longevity. Conclusions In conclusion, this meta-analysis indicates a significant association of five FOX03A gene polymorphisms with longevity, with the effects of rs2802292 and rs2764264 being male-specific. Further investigations are required to confirm these findings.

  17. Association between FOXO3A gene polymorphisms and human longevity: a meta-analysis.

    PubMed

    Bao, Ji-Ming; Song, Xian-Lu; Hong, Ying-Qia; Zhu, Hai-Li; Li, Cui; Zhang, Tao; Chen, Wei; Zhao, Shan-Chao; Chen, Qing

    2014-01-01

    Numerous studies have shown associations between the FOXO3A gene, encoding the forkhead box O3 transcription factor, and human or specifically male longevity. However, the associations of specific FOXO3A polymorphisms with longevity remain inconclusive. We performed a meta-analysis of existing studies to clarify these potential associations. A comprehensive search was conducted to identify studies of FOXO3A gene polymorphisms and longevity. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by comparing the minor and major alleles. A total of seven articles reporting associations of FOXO3A polymorphisms with longevity were identified and included in this meta-analysis. These comprised 11 independent studies with 5241 cases and 5724 controls from different ethnic groups. rs2802292, rs2764264, rs13217795, rs1935949 and rs2802288 polymorphisms were associated with human longevity (OR = 1.36, 95% CI = 1.10-1.69, P= 0.005; OR = 1.20, 95% CI = 1.04-1.37, P= 0.01; OR = 1.27, 95% CI = 1.10-1.46, P= 0.001; OR = 1.14, 95% CI = 1.01-1.27 and OR = 1.24, 95% CI = 1.07-1.43, P= 0.003, respectively). Analysis stratified by gender indicated significant associations between rs2802292, rs2764264 and rs13217795 and male longevity (OR = 1.54, 95% CI = 1.33-1.79, P < 0.001; OR = 1.38, 95% CI = 1.15-1.66, P= 0.001; and OR = 1.39, 95% CI = 1.15-1.67, P= 0.001), but rs2802292, rs2764264 and rs1935949 were not linked to female longevity. Moreover, our study showed no association between rs2153960, rs7762395 or rs13220810 polymorphisms and longevity. In conclusion, this meta-analysis indicates a significant association of five FOXO3A gene polymorphisms with longevity, with the effects of rs2802292 and rs2764264 being male-specific. Further investigations are required to confirm these findings.

  18. Dopamine D2 receptor gene polymorphisms and externalizing behaviors in children and adolescents.

    PubMed

    Della Torre, Osmar Henrique; Paes, Lúcia Arisaka; Henriques, Taciane Barbosa; de Mello, Maricilda Palandi; Celeri, Eloisa Helena Rubello Valler; Dalgalarrondo, Paulo; Guerra-Júnior, Gil; Santos-Júnior, Amilton Dos

    2018-05-02

    Dopamine is involved in several cerebral physiological processes, and single nucleotide polymorphisms (SNP) in the dopamine D2 receptor gene (DRD2) have been associated with numerous neurological and mental disorders, including those involving alterations in cognitive and emotional processes. The aim of this study was to evaluate the association between the SNPs c.957C > T (rs6277) and c.-585A > G (rs1799978) in the DRD2 gene and behavioral characteristics of children and adolescents based on an inventory of the Child Behavior Checklist (CBCL). Children and adolescents between 8 and 20 years old who were clinically followed-up were genotyped for the SNPs c.957C > T and c.-585A > G, and related to data of the CBCL/6-18 scale assessment performed with the help of caregivers. The chi-squared test was used to assess the differences in the frequencies of the C and T alleles in the polymorphism c.957C > T and of the A and G alleles in the polymorphism c.-585A > G with respect to the grouped CBCL scores at a significance level of 5%. Multiple logistic regression models were performed, to control whether sex and/or ethnicity could influence the results. Eighty-five patients were assessed overall, and the presence of the T allele (C/T and T/T) of DRD2 c.957C > T polymorphism was found to be significantly associated with the occurrence of defiant and oppositional problems and with attention and hyperactivity problems. There were no associations detected with polymorphism DRD2 c.-585A > G polymorphism. Both SNPs were in Hardy-Weinberg-equilibrium. Although the findings of this study are preliminary, due to its small number of participants, the presence of T allele (C/T, T/T) in c.957C > T SNP was associated with difficulty in impulse control, self-control of emotions, and conduct adjustment, which can contribute to improving the identification of mental and behavioral phenotypes associated with gene expression.

  19. Polymorphism of angiotensin-converting enzyme gene in sarcoidosis.

    PubMed

    Arbustini, E; Grasso, M; Leo, G; Tinelli, C; Fasani, R; Diegoli, M; Banchieri, N; Cipriani, A; Gorrini, M; Semenzato, G; Luisetti, M

    1996-02-01

    Sarcoidosis is the disease in which increased levels of serum Angiotensin-converting enzyme (sACE) are most often detected. It has recently been shown that the deletion (D) or the insertion (I) of a 250bp-DNA fragment in the ACE gene accounts for three main ACE genotypes (i.e., II, ID, and DD) and for 47% of total phenotypic variance in sACE level. The aim of our work was to investigate whether or not patients with sarcoidosis have an increased incidence of those ACE genotypes coding for highest sACE levels and to investigate whether or not sACE level in sarcoidosis is related to ACE genotypes. We studied 61 unrelated patients with sarcoidosis (test group) and 80 unrelated healthy control subjects (control group). The ACE I and D alleles were detected with polymerase chain reaction on genomic DNA. In the control group we found an ACE genotype distribution that agreed with the Hardy-Weinberg proportion. The ACE genotype distribution was not significantly different in the test group. There was no correlation between ACE genotype and roentgenologic stage of sarcoidosis. Plotting the sACE level in the control group against ACE genotype, we found a trend of increasing mean sACE value according to the order II < ID < DD. The same trend for ACE genotype was found in the test group, in which it also paralleled the trend of sACE values plotted against roentgenologic stage, according to the order Stage I < Stage II < Stage III. We conclude that in sarcoidosis the ACE genotype distribution is not altered. The trends for increasing sACE values in sarcoidosis according to both ACE genotype and roentgenologic stage would suggest that both mechanisms play a role in determining sACE level.

  20. Fas/FasL gene polymorphism in patients with Hashimoto's thyroiditis in Turkish population.

    PubMed

    Erdogan, M; Kulaksizoglu, M; Ganidagli, S; Berdeli, A

    2017-01-01

    Hashimoto's disease is a polygenic disorder with complex etiopathogenesis. Apoptosis is proposed as one of its mechanisms. The Fas/Fas ligand cascade represents a major pathway initiating apoptosis. This study aims to evaluate the influence of Fas and FasL gene polymorphism in Hashimoto's thyroiditis in Turkish population. A total of 112 patients with Hashimoto's thyroiditis and 112 cases of healthy control people were included in this study. The evaluation of genotype for Fas -670 A/G and FasL 843 C/T gene polymorphism was performed by using PCR-RFLP method. The FAS genotype and gene allele frequency distribution did differ between the control group (AA 36.6 %, AG 50.0 %, GG 13.4 %, A 61.6 %, G 38.4 %) and the Hashimoto's thyroiditis patients (AA 21.4 %, AG 50.9 %, GG 27.7 %, A 46.9 %, G 53.1 %) (p < 0.01). The evaluation of FasL genotype and gene allele frequency did not show statistically significant difference between the patient group (CC 27.7 %, CT 45.5 %, TT 26.8 %, C 50.4 %, T 49.6 %) and control group (CC 33.9 %, CT 44.6 %, TT 21,4 %, C 56.3 %, T 43.8 %) (p > 0.05). Gene polymorphism of Fas and G allele frequency may play a role in the regulation of apoptosis in thyroid autoimmune disorders. There is a need for further studies to clarify the genetic role of apoptosis in HT.

  1. Oxytocin and Opioid Receptor Gene Polymorphisms Associated with Greeting Behavior in Dogs.

    PubMed

    Kubinyi, Enikő; Bence, Melinda; Koller, Dora; Wan, Michele; Pergel, Eniko; Ronai, Zsolt; Sasvari-Szekely, Maria; Miklósi, Ádám

    2017-01-01

    Meeting humans is an everyday experience for most companion dogs, and their behavior in these situations and its genetic background is of major interest. Previous research in our laboratory reported that in German shepherd dogs the lack of G allele, and in Border collies the lack of A allele, of the oxytocin receptor gene (OXTR) 19208A/G single nucleotide polymorphism (SNP) was linked to increased friendliness, which suggests that although broad traits are affected by genetic variability, the specific links between alleles and behavioral variables might be breed-specific. In the current study, we found that Siberian huskies with the A allele approached a friendly unfamiliar woman less frequently in a greeting test, which indicates that certain polymorphisms are related to human directed behavior, but that the relationship patterns between polymorphisms and behavioral phenotypes differ between populations. This finding was further supported by our next investigation. According to primate studies, endogenous opioid peptide (e.g., endorphins) receptor genes have also been implicated in social relationships. Therefore, we examined the rs21912990 of the OPRM1 gene. Firstly, we found that the allele frequencies of Siberian huskies and gray wolves were similar, but differed from that of Border collies and German shepherd dogs, which might reflect their genetic relationship. Secondly, we detected significant associations between the OPRM1 SNP and greeting behavior among German shepherd dogs and a trend in Border collies, but we could not detect an association in Siberian huskies. Although our results with OXTR and OPRM1 gene variants should be regarded as preliminary due to the relatively low sample size, they suggest that (1) OXTR and OPRM1 gene variants in dogs affect human-directed social behavior and (2) their effects differ between breeds.

  2. Oxytocin and Opioid Receptor Gene Polymorphisms Associated with Greeting Behavior in Dogs

    PubMed Central

    Kubinyi, Enikő; Bence, Melinda; Koller, Dora; Wan, Michele; Pergel, Eniko; Ronai, Zsolt; Sasvari-Szekely, Maria; Miklósi, Ádám

    2017-01-01

    Meeting humans is an everyday experience for most companion dogs, and their behavior in these situations and its genetic background is of major interest. Previous research in our laboratory reported that in German shepherd dogs the lack of G allele, and in Border collies the lack of A allele, of the oxytocin receptor gene (OXTR) 19208A/G single nucleotide polymorphism (SNP) was linked to increased friendliness, which suggests that although broad traits are affected by genetic variability, the specific links between alleles and behavioral variables might be breed-specific. In the current study, we found that Siberian huskies with the A allele approached a friendly unfamiliar woman less frequently in a greeting test, which indicates that certain polymorphisms are related to human directed behavior, but that the relationship patterns between polymorphisms and behavioral phenotypes differ between populations. This finding was further supported by our next investigation. According to primate studies, endogenous opioid peptide (e.g., endorphins) receptor genes have also been implicated in social relationships. Therefore, we examined the rs21912990 of the OPRM1 gene. Firstly, we found that the allele frequencies of Siberian huskies and gray wolves were similar, but differed from that of Border collies and German shepherd dogs, which might reflect their genetic relationship. Secondly, we detected significant associations between the OPRM1 SNP and greeting behavior among German shepherd dogs and a trend in Border collies, but we could not detect an association in Siberian huskies. Although our results with OXTR and OPRM1 gene variants should be regarded as preliminary due to the relatively low sample size, they suggest that (1) OXTR and OPRM1 gene variants in dogs affect human-directed social behavior and (2) their effects differ between breeds. PMID:28936190

  3. Tryptophan Hydroxylase 2 Gene Polymorphism in Anxiety and Depressive Disorder in Kashmiri Population

    PubMed Central

    Shoib, Sheikh; Shah, Tabindah; Mushtaq, Sahil

    2014-01-01

    Background: The gene of tryptophan hydroxylase is widely recognized as a major candidate gene in many psychiatric disorders. However, no study has been done which investigates tryptophan hydroxylase 2 gene polymorphism in anxiety and depressive disorders in Kashmiri population (India). Objectives: To study tryptophan hydroxylase 2 (TPH2) C 11993 A gene polymorphism in anxiety and depressive disorders. Method: Sixty patients of depression disorder, 60 patients of anxiety disorder and 40 unrelated healthy volunteers (control) were studied in a case control design. Polymorphism was determined using polymerase chain reaction (PCR) and agarose gel electrophoresis after digestion with HAP II enzyme. Genotypes and allele frequencies were compared using Chi-square tests, Fischer’s exact test, odds ratio, 95% confidence interval (C.I) and p-value of <0.05 was considered to be statistical significant. Results: The mean age ± SD of anxiety, depression and control group was 32.73±10.99, 32.20±10 and 29.75±10.12 respectively and the difference was found to be statistically non significant (p=0.349).The mean HAM-A (Hamilton rating scale for anxiety) score and HAM-D (Hamilton rating scale for depression) score was high in both groups (anxiety and depression) and found to be statistically significant (p=0.001).Depression group had AA genotype (55.2%) than control (37.5%) and was found to be statistically non significant (p=0.890).Comparison of allelic frequency revealed no association of A allele in anxiety group (76.67%) compared with control (75.5%) and was found to be statistically non significant (p= 0.866), OR 1.09 (0.56-2.11). Conclusion: TPH2C 11993 A gene was not found to be associated with major depressive disorder (MDD) and anxiety disorder in Kashmiri population. PMID:25121048

  4. Beta 2 adrenergic receptor gene restriction fragment length polymorphism and bronchial asthma.

    PubMed Central

    Ohe, M.; Munakata, M.; Hizawa, N.; Itoh, A.; Doi, I.; Yamaguchi, E.; Homma, Y.; Kawakami, Y.

    1995-01-01

    BACKGROUND--Beta 2 adrenergic dysfunction may be one of the underlying mechanisms responsible for atopy and bronchial asthma. The gene encoding the human beta 2 adrenergic receptor (beta 2ADR) has recently been isolated and sequenced. In addition, a two allele polymorphism of this receptor gene has been identified in white people. A study was carried out to determine whether this polymorphism is functionally important and has any relation to airways responsiveness, atopy, or asthma. METHODS--The subjects studied were 58 family members of four patients with atopic asthma. Restriction fragment length polymorphism (RFLP) with Ban-I digestion of the beta 2ADR gene was detected by a specific DNA probe with Southern blot analysis. Airways responses to inhaled methacholine and the beta 2 agonist salbutamol, the skin prick test, and serum IgE levels were also examined and correlated to the beta 2ADR gene RFLP. In addition, measurements of cAMP responses to isoproterenol in peripheral mononuclear cells were performed in 22 healthy subjects whose genotype for beta 2ADR was known. RESULTS--A two allele polymorphism (2.3 kb and 2.1 kb) of the beta 2ADR gene was detected in the Japanese population. Family members without allele 2.3 kb (homozygote of allele 2.1 kb) had lower airways responses to inhaled salbutamol than those with allele 2.3 kb. The incidence of asthma was higher in those without allele 2.3 kb than in those with allele 2.3 kb. The beta 2ADR gene RFLP had no relation to airways responses to methacholine and atopic status. cAMP responses in peripheral mononuclear cells of the subjects without allele 2.3 kb tended to be lower than those of the subjects with allele 2.3 kb. CONCLUSIONS--These results suggest that Ban-I RFLP of the beta 2ADR gene may have some association with the airways responses to beta 2 agonists and the incidence of bronchial asthma. Images PMID:7785006

  5. HDC gene polymorphisms are associated with age at natural menopause in Caucasian women

    SciTech Connect

    Zhang Feng; Osteoporosis Research Center, Creighton University Medical Center, Omaha, NE 68131; Xiong Donghai

    2006-10-06

    Histidine decarboxylase gene (HDC) encodes histidine decarboxylase which is the crucial enzyme for the biosynthesis of histidine. Studies have shown that histamine is likely to be involved in the regulation of reproduction system. To find the possible correlation between HDC gene and AANM (age at natural menopause), we selected 265 postmenopausal women from 131 nuclear families and performed a transmission disequilibrium test. Significant within-family associations with AANM for SNP rs854163 and SNP rs854158 of HDC gene were observed (P values = 0.0018 and 0.0197, respectively). After 1000 permutations, SNP rs854163 still remained significant within-family association with AANM. Consistently, we alsomore » detected a significant within-family association between haplotype block 2 (defined by SNP rs854163 and rs860526) and AANM in the haplotype analyses (P value = 0.0397). Our results suggest that the HDC gene polymorphisms are significantly associated with AANM in Caucasian women.« less

  6. Statistics on gene-based laser speckles with a small number of scatterers: implications for the detection of polymorphism in the Chlamydia trachomatis omp1 gene

    NASA Astrophysics Data System (ADS)

    Ulyanov, Sergey S.; Ulianova, Onega V.; Zaytsev, Sergey S.; Saltykov, Yury V.; Feodorova, Valentina A.

    2018-04-01

    The transformation mechanism for a nucleotide sequence of the Chlamydia trachomatis gene into a speckle pattern has been considered. The first and second-order statistics of gene-based speckles have been analyzed. It has been demonstrated that gene-based speckles do not obey Gaussian statistics and belong to the class of speckles with a small number of scatterers. It has been shown that gene polymorphism can be easily detected through analysis of the statistical characteristics of gene-based speckles.

  7. Interaction between the APOC3 gene promoter polymorphisms, saturated fat intake and plasma lipoproteins.

    PubMed

    Brown, Sherine; Ordovás, José M; Campos, Hannia

    2003-10-01

    To test the hypothesis that APOC3 gene polymorphisms modulate the effect of saturated fat (SAT) intake on plasma lipoproteins and LDL size. We studied 336 randomly selected residents from Costa Rica. APOC3 polymorphisms were genotyped in the promoter region (T-455C, T-625del) and the C3238G 3' untranslated region (UTR). Dietary intake was assessed by a validated food-frequency questionnaire (FFQ) and median saturated fat intake (11%) was used to define low and high exposure to saturated fat. Allele frequencies were 0.49, 0.51 and 0.19 for the APOC3-455C, -625de1, and APOC3 3238G alleles, respectively. Significant gene-diet interactions were found for total (P<0.0004) and LDL cholesterol (P<0.01). In homozygotes for the APOC3-455T-625T alleles, saturated fat intake was associated with a 13% increase in total cholesterol (P<0.001) and a 20% increase in LDL cholesterol (P<0.001). In contrast, no association between plasma lipoproteins and saturated fat intake was found among carriers of the APOC3-455C-625del allele. The APOC3 3238G UTR allele did not modify the observed association. Compared to a diet high in saturated fat, a habitually low saturated fat diet is associated with a beneficial lipoprotein profile only among homozygotes of the APOC3 promoter 455T-625T polymorphism.

  8. Collagen Ialpha1 and vitamin D receptor gene polymorphisms in South African whites, blacks and Indians.

    PubMed

    Ojwang, P J; Pegoraro, R J; Rom, L; Lanning, P

    2001-11-01

    To determine whether polymorphic differences exist between black, white and Indian South Africans in genes associated with bone mineral density and osteoporosis. Genes selected were the vitamin D receptor (Apa I and Taq I polymorphisms) and collagen (Sp I transcription factor polymorphism) using standard molecular biology techniques. Department of Chemical Pathology, Nelson R Mandela School of Medicine, University of Natal, Durban, South Africa. Healthy male and female blood donors living in the Durban metropolitan region, South Africa. The group comprised black Africans (n=264), white Caucasians (n=247) and Asians of Indian origin (n=194). No significant differences in genotypes were seen between white and Indian subjects. Blacks had a significantly higher frequency of the TT Taq I genotype and a significantly lower frequency of the Ss Sp I genotype. No ss genotype was detected in blacks. The very low frequency of the collagen Sp I s allele and higher frequency of the VDR T allele in blacks may be associated with the lower incidence of osteoporosis in this ethnic group.

  9. The association of the metalloproteinase-3 gene promoter polymorphisms and the middle cerebral artery stenosis.

    PubMed

    Fu, Chunli; Xing, Yingqi; Song, Xiaonan

    2011-04-01

    To investigate the association of single nucleotide polymorphism in the matrix metalloproteinase-3 (MMP3) gene promoter with the susceptibility to the middle cerebral artery stenosis. A case-control study was performed by determining the genotype of MMP3 gene promoter region using polymerase chain reaction-restriction fragment length polymorphism in 119 patients with middle cerebral artery stenosis documented by transcranial Doppler compared to 92 control patients. The frequencies of 5A and 6A alleles in MMP3 promoter region were 16.0 and 84.0% respectively in case group compared to 15.8 and 84.2% in control group with no significant difference between the two groups (P > 0.05). No significant difference was also observed in the distribution of genotypes 5A/5A,5A/6A, and 6A/6A between middle cerebral artery stenosis and control groups. Compared to 5A/5A + 5A/6A genotypes,the 6A/6A genotype did not significantly modify the risk of developing the middle cerebral artery stenosis. The MMP3-1171 dupA promoter polymorphisms are not valuable markers of susceptibility of the middle cerebral artery stenosis in this sample of population studied.

  10. Relationship between IL1 gene polymorphisms and periodontal disease in Japanese women.

    PubMed

    Tanaka, Keiko; Miyake, Yoshihiro; Hanioka, Takashi; Arakawa, Masashi

    2014-04-01

    Epidemiological evidence on the relationship between IL1A and/or IL1B polymorphisms and periodontal disease is inconsistent. We investigated associations between three IL1 single-nucleotide polymorphisms (SNPs) in genes encoding interleukin (IL) -1α (rs1800587) and IL-1β (rs1143634 and rs16944) and the risk of periodontal disease among young Japanese women. A case-control study was performed with a total of 1150 women, including 131 subjects who had at least one tooth with a probing pocket depth of 4 mm or deeper and 1019 periodontally healthy controls. Compared with a reference group of women with the GG genotype of SNP rs16944, those with the GA genotype had a significantly reduced risk of periodontal disease, while there was no significant relationship between the AA genotype and periodontal disease. No evident relationships were observed between SNP rs1800587 or rs1143634 and periodontal disease. Our study did not reveal any evidence of interaction between the IL1 polymorphisms and smoking. The results of this study showed that the heterozygous variant genotype of the IL1 rs16944 was significantly associated with a reduced risk of periodontal disease in young Japanese women. Smoking did not significantly modify the gene-disease associations under study.

  11. Interleukin-10 -1082 gene polymorphism and susceptibility to cervical cancer among Japanese women.

    PubMed

    Matsumoto, Koji; Oki, Akinori; Satoh, Toyomi; Okada, Satoshi; Minaguchi, Takeo; Onuki, Mamiko; Ochi, Hiroyuki; Nakao, Sari; Sakurai, Manabu; Abe, Azusa; Hamada, Hiromi; Yoshikawa, Hiroyuki

    2010-11-01

    Polymorphisms in cytokine genes can influence immune responses to human papillomavirus infection, possibly modifying risks of cervical cancer. Using an amplification refractory mutation system-polymerase chain reaction method, we analyzed a single nucleotide polymorphism (A/G) at position -1082 in interleukin-10 promoter region in 440 Japanese women: 173 women with normal cytology, 163 women with cervical intraepithelial neoplasia and 104 women with invasive cervical cancer. The carrier frequency of interleukin-10 -1082 G alleles associated with higher interleukin-10 production increased with disease severity: 9.8% for normal cytology; 19.6% for cervical intraepithelial neoplasia; 29.8% for invasive cervical cancer (P for trend < 0.001). Among cytologically normal women, human papillomavirus infections were more common in those who were positive for an interleukin-10 -1082 G allele (P = 0.04). In conclusion, our data suggest that interleukin-10 -1082 gene polymorphism may serve as a marker of genetic susceptibility to cervical cancer among Japanese women.

  12. The IFN-gamma +874T/A gene polymorphism is associated with retinochoroiditis toxoplasmosis susceptibility.

    PubMed

    Albuquerque, Maíra Cavalcanti de; Aleixo, Ana Luisa Quintella do Couto; Benchimol, Eliezer Israel; Leandro, Ana Cristina Câmara S; das Neves, Leandro Batista; Vicente, Regiane Trigueiro; Bonecini-Almeida, Maria da Glória; Amendoeira, Maria Regina Reis

    2009-05-01

    Toxoplasmosis is a worldwide zoonosis that generally produces an asymptomatic infection. In some cases, however, toxoplasmosis infection can lead to ocular damage. The immune system has a crucial role in both the course of the infection and in the evolution of toxoplasmosis disease. In particular, IFN-gamma plays an important role in resistance to toxoplasmosis. Polymorphisms in genes encoding cytokines have been shown to have an association with susceptibility to parasitic diseases. The aim of this work was to analyse the occurrence of polymorphisms in the gene encoding IFN-gamma (+874T/A) among Toxoplasma gondii seropositive individuals, including those with ocular lesions caused by the parasite, from a rural population of Santa Rita de Cássia, Barra Mansa, state of Rio de Janeiro, Brazil. Further, we verified which of these polymorphisms could be related to susceptibility to the development of ocular toxoplasmosis. This study included 34 individuals with ocular toxoplasmosis (ocular group) and 134 without ocular lesions (control group). The differences between A and T allele distributions were not statistically significant between the two groups. However, we observed that a higher frequency of individuals from the ocular group possessed the A/A genotype, when compared with the control group, suggesting that homozygocity for the A allele could enhance susceptibility to ocular toxoplasmosis in T. gondii infection.

  13. Impacts of ICAM-1 gene polymorphisms on urothelial cell carcinoma susceptibility and clinicopathologic characteristics in Taiwan.

    PubMed

    Wang, Shian-Shiang; Hsieh, Ming-Ju; Ou, Yen-Chuan; Chen, Chuan-Shu; Li, Jian-Ri; Hsiao, Pei-Ching; Yang, Shun-Fa

    2014-08-01

    Intercellular adhesion molecule (ICAM)-1, a cell adhesion molecule, is reportedly overexpressed in several cancers and may contribute to tumorgenesis and metastasis. The current study explored the effect of ICAM-1 gene polymorphisms on the susceptibility of developing urothelial cell carcinoma (UCC) and the clinicopathological status. A total of 558 participants, including 279 healthy people and 279 patients with UCC, were recruited for this study. Four single-nucleotide polymorphisms of the ICAM-1 gene were assessed by a real-time polymerase chain reaction with the TaqMan assay. After adjusting for other covariants, the individuals carrying at least one G allele at ICAM-1 rs5498 had a 1.603-fold risk of developing UCC than did wild-type (AA) carriers. Furthermore, UCC patients who carried at least one G allele at rs5498 had a higher invasive stage risk (p < 0.05) than did patients carrying the wild-type allele. In conclusion, the rs5498 polymorphic genotypes of ICAM-1 might contribute to the prediction of susceptibility to and pathological development of UCC. This is the first study to provide insight into risk factors associated with ICAM-1 variants in carcinogenesis of UCC in Taiwan.

  14. ADRB2 and LEPR gene polymorphisms: synergistic effects on the risk of obesity in Japanese.

    PubMed

    Pereira, Tiago V; Mingroni-Netto, Regina C; Yamada, Yoshiji

    2011-07-01

    The objective of the present study was to validate a recently reported synergistic effect between variants located in the leptin receptor (LEPR) gene and in the β-2 adrenergic receptor (ADRB2) gene on the risk of overweight/obesity. We studied a middle-aged/elderly sample of 4,193 nondiabetic Japanese subjects stratified according gender (1,911 women and 2,282 men). The LEPR Gln223Arg (rs1137101) variant as well as both ADRB2 Arg16Gly (rs1042713) and Gln27Glu (rs1042714) polymorphisms were analyzed. The primary outcome was the risk of overweight/obesity defined as BMI ≥25 kg/m(2), whereas secondary outcomes included the risk of a BMI ≥27 kg/m(2) and BMI as a continuous variable. None of the studied polymorphisms showed statistically significant individual effects, regardless of the group or phenotype studied. Haplotype analysis also did not disclose any associations of ADRB2 polymorphisms with BMI. However, dimensionality reduction-based models confirmed significant interactions among the investigated variants for BMI as a continuous variable as well as for the risk of obesity defined as BMI ≥27 kg/m(2). All disclosed interactions were found in men only. Our results provide external validation for a male specific ADRB2-LEPR interaction effect on the risk of overweight/obesity, but indicate that effect sizes associated with these interactions may be smaller in the population studied.

  15. An Indel Polymorphism in the Hybrid Incompatibility Gene Lethal Hybrid Rescue of Drosophila Is Functionally Relevant

    PubMed Central

    Maheshwari, Shamoni; Barbash, Daniel A.

    2012-01-01

    Hybrid incompatibility (HI) genes are frequently observed to be rapidly evolving under selection. This observation has led to the attractive conjecture that selection-derived protein-sequence divergence is culpable for incompatibilities in hybrids. The Drosophila simulans HI gene Lethal hybrid rescue (Lhr) is an intriguing case, because despite having experienced rapid sequence evolution, its HI properties are a shared function inherited from the ancestral state. Using an unusual D. simulans Lhr hybrid rescue allele, Lhr2, we here identify a conserved stretch of 10 amino acids in the C terminus of LHR that is critical for causing hybrid incompatibility. Altering these 10 amino acids weakens or abolishes the ability of Lhr to suppress the hybrid rescue alleles Lhr1 or Hmr1, respectively. Besides single-amino-acid substitutions, Lhr orthologs differ by a 16-aa indel polymorphism, with the ancestral deletion state fixed in D. melanogaster and the derived insertion state at very high frequency in D. simulans. Lhr2 is a rare D. simulans allele that has the ancestral deletion state of the 16-aa polymorphism. Through a series of transgenic constructs we demonstrate that the ancestral deletion state contributes to the rescue activity of Lhr2. This indel is thus a polymorphism that can affect the HI function of Lhr. PMID:22865735

  16. Polymorphisms in DENND1B gene are associated with asthma and atopy phenotypes in Brazilian children.

    PubMed

    Fiuza, Bianca S D; Silva, Milca de J; Alcântara-Neves, Neuza M; Barreto, Maurício L; Costa, Ryan Dos S; Figueiredo, Camila A

    2017-10-01

    Asthma is a heterogeneous disease associated with a complex basis involving environmental factors and individual variabilities. The DENN Domain Containing 1B (DENND1B) gene has an important role on T cell receptor (TCR) down-regulation on Th2 cells and studies have shown that mutations or loss of this factor can be associated with increased Th2 responses and asthma. The aim of this work is to evaluate the association of polymorphisms in the DENND1B with asthma and allergy markers phenotypes in Brazilian children. Genotyping was performed using a commercial panel from Illumina (2.5 Human Omni bead chip) in 1309 participants of SCAALA (Social Change, Asthma, Allergy in Latin American) program. Logistic regressions for asthma and atopy markers were performed using PLINK software 1.9. The analyzes were adjusted for sex, age, helminth infections and ancestry markers. The DENND1B gene was associated with different phenotypes such as severe asthma and atopic markers (specific IgE production, skin prick test and IL-13 production). Among the 166 SNPs analyzed, 72 were associated with asthma and/or allergy markers. In conclusion, polymorphisms in the DENND1B are significantly associated with development of asthma and atopy and these polymorphisms can influence DENND1B expression and consequently, asthma. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Analysis of promoter polymorphism in monoamine oxidase A (MAOA) gene in completed suicide on Slovenian population.

    PubMed

    Uršič, Katarina; Zupanc, Tomaž; Paska, Alja Videtič

    2018-04-23

    Suicide is a well-defined public health problem and is a complex phenomenon influenced by a number of different risk factors, including genetic ones. Numerous studies have examined serotonin system genes. Monoamine oxidase A (MAO-A) is an outer mitochondrial membrane enzyme which is involved in the metabolic pathway of serotonin degradation. Upstream variable number of tandem repeats (uVNTR) in the promoter region of MAOA gene affects the activity of transcription. In the present study we genotyped MAOA-uVNTR polymorphism in 266 suicide victims and 191 control subjects of Slovenian population, which ranks among the European and world populations with the highest suicide rate. Genotyping was performed with polymerase chain reaction and agarose gel electrophoresis. Using a separate statistical analysis for female and male subjects we determined the differences in genotype distributions of MAOA-uVNTR polymorphism between the studied groups. Statistical analysis showed a trend towards 3R allele and suicide, and associated 3R allele with non-violent suicide method on stratified data (20 suicide victims). This is the first study associating highly suicidal Slovenian population with MAOA-uVNTR polymorphism. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. The Vitamin D Receptor (VDR) Gene Polymorphisms in Turkish Brain Cancer Patients

    PubMed Central

    Toptaş, Bahar; Kafadar, Ali Metin; Cacina, Canan; Turan, Saime; Yurdum, Leman Melis; Yiğitbaşı, Nihal; Gökçe, Muhammed Oğuz; Zeybek, Ümit; Yaylım, Ilhan

    2013-01-01

    Objective. It has been stated that brain cancers are an increasingly serious issue in many parts of the world. The aim of our study was to determine a possible relationship between Vitamin D receptor (VDR) gene polymorphisms and the risk of glioma and meningioma. Methods. We investigated the VDR Taq-I and VDR Fok-I gene polymorphisms in 100 brain cancer patients (including 44 meningioma cases and 56 glioma cases) and 122 age-matched healthy control subjects. This study was performed by polymerase chain reaction-based restriction fragment length polymorphism (RF LP). Results. VDR Fok-I ff genotype was significantly increased in meningioma patients (15.9%) compared with controls (2.5%), and carriers of Fok-I ff genotype had a 6.47-fold increased risk for meningioma cases. There was no significant difference between patients and controls for VDR Taq-I genotypes and alleles. Conclusions. We suggest that VDR Fok-I genotypes might affect the development of meningioma. PMID:23691496

  19. Novel Association of WNK4 Gene, Ala589Ser Polymorphism in Essential Hypertension, and Type 2 Diabetes Mellitus in Malaysia.

    PubMed

    Ghodsian, Nooshin; Ismail, Patimah; Ahmadloo, Salma; Heidari, Farzad; Haghvirdizadeh, Polin; Ataollahi Eshkoor, Sima; Etemad, Ali

    2016-01-01

    With-no-lysine (K) Kinase-4 (WNK4) consisted of unique serine and threonine protein kinases, genetically associated with an autosomal dominant form of hypertension. Argumentative consequences have lately arisen on the association of specific single nucleotide polymorphisms of WNK4 gene and essential hypertension (EHT). The aim of this study was to determine the association of Ala589Ser polymorphism of WNK4 gene with essential hypertensive patients in Malaysia. WNK4 gene polymorphism was specified utilizing mutagenically separated polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) method in 320 subjects including 163 cases and 157 controls. Close relation between Ala589Ser polymorphism and elevated systolic and diastolic blood pressure (SBP and DBP) was recognized. Sociodemographic factors including body mass index (BMI), age, the level of fasting blood sugar (FBS), low density lipoprotein (LDL), and triglyceride (TG) in the cases and healthy subjects exhibited strong differences (p < 0.05). The distribution of allele frequency and genotype of WNK4 gene Ala589Ser polymorphism showed significant differences (p < 0.05) between EHT subjects with or without type 2 diabetes mellitus (T2DM) and normotensive subjects, statistically. The WNK4 gene variation influences significantly blood pressure increase. Ala589Ser probably has effects on the enzymic activity leading to enhanced predisposition to the disorder.

  20. Roles of beta2-adrenergic receptor gene polymorphisms in a Turkish population with obstructive sleep apnea syndrome or obesity.

    PubMed

    Gök, I; Celebi, I; Hüseyinoğlu, N; Ozic, C

    2014-10-20

    We determined the distribution of the Arg16Gly and Gln27Glu polymorphisms of the beta-2 adrenergic receptor gene (ADRB2) in patients with obstructive sleep apnea syndrome as well as a control group in Northeastern Turkey. A total of 52 patients diagnosed with obstructive sleep apnea in a sleep laboratory and 78 control subjects were examined. Peripheral blood samples were taken from patients diagnosed with obstructive sleep apnea by polysomnography. DNA was extracted from blood samples and amplified using polymerase chain reaction. Amplification products were digested with restriction enzymes to investigate gene polymorphisms. Restriction products were extracted from agarose gel electrophoresis and polymorphisms were analyzed using gel images. The Arg16Gly polymorphism was observed in 18 of 52 patients and in 23 of 78 controls. The Gln27Glu polymorphism was observed in 21 of 52 patients and in 28 of 78 controls. In conclusion, there was no correlation among polymorphic frequencies between patient and control groups. Based on the results, these polymorphisms do not contribute to the clinical diagnosis of this syndrome. However, the distribution of Arg16Gly vs Gln27Glu polymorphisms may contribute to obesity in patients with a body mass index greater than 30 (P < 0.05). Different results may be obtained if the parameters of obstructive sleep apnea disease are changed.

  1. Association of Ugrp2 gene polymorphisms with adenoid hypertrophy in the pediatric population.

    PubMed

    Atilla, Mahmut Huntürk; Özdaş, Sibel; Özdaş, Talih; Baştimur, Sibel; Muz, Sami Engin; Öz, Işılay; Kurt, Kenan; İzbirak, Afife; Babademez, Mehmet Ali; Vatandaş, Nilgün

    2017-08-01

    Adenoid hypertrophy is a condition that presents itself as the chronic enlargement of adenoid tissues; it is frequently observed in the pediatric population. The Ugrp2 gene, a member of the secretoglobin superfamily, encodes a low-molecular weight protein that functions in the differentiation of upper airway epithelial cells. However, little is known about the association of Ugrp2 genetic variations with adenoid hypertrophy. The aim of this study is to investigate the association of single nucleotide polymorphisms in the Ugrp2 gene with adenoid hypertrophy and its related phenotypes. A total of 219 children, comprising 114 patients suffering from adenoid hypertrophy and 105 healthy patients without adenoid hypertrophy, were enrolled in this study. Genotypes of the Ugrp2 gene were determined by DNA sequencing. We identified four single nucleotide polymorphisms (IVS1-189G>A, IVS1-89T>G, c.201delC, and IVS2-15G>A) in the Ugrp2 gene. Our genotype analysis showed that the Ugrp2 (IVS1-89T>G) TG and (c.201delC) CdelC genotypes and their minor alleles were associated with a considerable increase in the risk of adenoid hypertrophy compared with the controls (p=0.012, p=0.009, p=0.013, and p=0.037, respectively). Furthermore, Ugrp2 (GTdelCG, GTdelCA) haplotypes were significantly associated with adenoid hypertrophy (four single nucleotide polymorphisms ordered from 5' to 3'; p=0.0001). Polymorfism-Polymorfism interaction analysis indicated a strong interaction between combined genotypes of the Ugrp2 gene contributing to adenoid hypertrophy, as well as an increased chance of its diagnosis (p<0.0001). In addition, diplotypes carrying the mutant Ugrp2 (c.201delC) allele were strongly associated with an increased risk of adenoid hypertrophy with asthma and adenoid hypertrophy with allergies (p=0.003 and p=0.0007, respectively). Some single nucleotide polymorphisms and their combinations in the Ugrp2 gene are associated with an increased risk of developing adenoid hypertrophy

  2. Genomic polymorphism, recombination, and linkage disequilibrium in human major histocompatibility complex-encoded antigen-processing genes.

    PubMed Central

    van Endert, P M; Lopez, M T; Patel, S D; Monaco, J J; McDevitt, H O

    1992-01-01

    Recently, two subunits of a large cytosolic protease and two putative peptide transporter proteins were found to be encoded by genes within the class II region of the major histocompatibility complex (MHC). These genes have been suggested to be involved in the processing of antigenic proteins for presentation by MHC class I molecules. Because of the high degree of polymorphism in MHC genes, and previous evidence for both functional and polypeptide sequence polymorphism in the proteins encoded by the antigen-processing genes, we tested DNA from 27 consanguineous human cell lines for genomic polymorphism by restriction fragment length polymorphism (RFLP) analysis. These studies demonstrate a strong linkage disequilibrium between TAP1 and LMP2 RFLPs. Moreover, RFLPs, as well as a polymorphic stop codon in the telomeric TAP2 gene, appear to be in linkage disequilibrium with HLA-DR alleles and RFLPs in the HLA-DO gene. A high rate of recombination, however, seems to occur in the center of the complex, between the TAP1 and TAP2 genes. Images PMID:1360671

  3. Association study of interferon gamma (IFN-γ) +874T/A gene polymorphism in patients with paranoid schizophrenia.

    PubMed

    Paul-Samojedny, Monika; Owczarek, Aleksander; Suchanek, Renata; Kowalczyk, Malgorzata; Fila-Danilow, Anna; Borkowska, Paulina; Kucia, Krzysztof; Kowalski, Jan

    2011-03-01

    Schizophrenia is a multifactorial disease with changes affecting the immune system. Dysregulation of the cytokine network in schizophrenia has been well documented. Such changes may occur due to disturbances in cytokine levels that are linked to polymorphisms of cytokine genes. However, research in the role of cytokine gene polymorphisms in schizophrenia has been surprisingly scanty. The aim of this study was to identify, in a case control study, whether polymorphism of IFN-γ gene is a risk factor for the development of paranoid schizophrenia. To the best of our knowledge, this is the first study that examines the association between the IFN-γ gene polymorphism and psychopathological symptoms in patients with paranoid schizophrenia. Polymorphism of IFN-γ (+874T/A, rs 62559044) in schizophrenic patients (n=179), as well as healthy individuals (n=196), both Polish residents, was genotyped using AS-PCR method. Of note, when analyzing the results, we took into consideration the gender of studied individuals. Surprisingly, a single-nucleotide polymorphism in the first intron of the IFN-γ gene was found to be associated with paranoid schizophrenia in males, but not in females. The presence of allele A at position +874 in the IFN-γ gene correlates with 1.66-fold higher risk of paranoid schizophrenia development in males. Differences in the genotypes may have an important role in determining the level of I gene transcription. Because other polymorphisms have been demonstrated to influence IFN-γ transcription, further analysis is necessary to clarify the role of this gene in the pathogenesis of paranoid schizophrenia.

  4. Interleukin-1 gene polymorphisms in chronic gastritis patients infected with Helicobacter pylori as risk factors of gastric cancer development.

    PubMed

    Hnatyszyn, Andrzej; Wielgus, Karolina; Kaczmarek-Rys, Marta; Skrzypczak-Zielinska, Marzena; Szalata, Marlena; Mikolajczyk-Stecyna, Joanna; Stanczyk, Jerzy; Dziuba, Ireneusz; Mikstacki, Adam; Slomski, Ryszard

    2013-12-01

    Epidemiological investigations indicated association of the Helicobacter pylori infections with the occurrence of inflammatory conditions of the gastric mucosa and development of chronic gastritis and intestinal type of gastric cancer. IL1A and IL1B genes have been proposed as key factors in determining risk of gastritis and malignant transformation. The aim of this paper was to evaluate association of interleukin-1 gene polymorphisms with chronic gastritis, atrophy, intestinal metaplasia, dysplasia and intestinal type of gastric cancer in H. pylori-infected patients. Patients subjected to analysis represent group of 144 consecutive cases that suffered from dyspepsia with coexisting infection of H. pylori and chronic gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia or gastric cancer. Molecular studies involved analysis of -889C>T polymorphism of IL1A gene and +3954C>T polymorphism of IL1B gene. Statistical analysis of association of polymorphism -889C>T of gene IL1A with changes in gastric mucosa showed lack of significance, whereas +3954C>T polymorphism of IL1B gene showed significant association. Frequency of allele T of +3954C>T polymorphism of IL1B gene was higher in group of patients with chronic gastritis, atrophy, intestinal metaplasia, dysplasia or intestinal type of gastric cancer (32.1 %) as compared with population group (23 %), χ(2) = 4.61 and p = 0.03. This corresponds to odds ratio: 1.58, 95 % CI: 1.04-2.4. Our results indicate that +3954C>T polymorphism of IL1B gene increase susceptibility to inflammatory response of gastric mucosa H. pylori-infected patients and plays a significant role in the development of chronic gastritis, atrophy, intestinal metaplasia, dysplasia and the initiation of carcinogenesis.

  5. Polymorphisms of the ghrelin/obestatin gene and ghrelin levels in Chinese children with short stature.

    PubMed

    Zou, Chao Chun; Huang, Ke; Liang, Li; Zhao, Zheng Yan

    2008-07-01

    To investigate the role of ghrelin and polymorphisms of ghrelin/obestatin gene in children with short stature. A total of 117 GH deficient (GHD) and 81 idiopathic short stature (ISS) children were studied. The controls consisted of 125 age and gender-matched healthy children. The Arg51Gln, Leu72Met and Gln90Leu polymorphisms were genotyped using MassArray and total plasma ghrelin was measured by radioimmunoassay. In this study, the frequency of the Arg51Gln polymorphism was very low (0% in controls and 1.0% in patients). The frequency of the Gln90Leu polymorphism was 1.6% in controls and 0.5% in patients, respectively. Higher frequencies of Leu72Met (34.4% in controls and 39.9% in patients) and Met72Met genotypes (4.0% in controls and 2.0% in patients) were found. The differences in the Arg51Gln, Leu72Met or Gln90Leu genotypes and allele frequencies between patients and controls were not significant. Also, there were no significant differences in the Leu72Met genotypes and allele frequencies between GHD and ISS subgroups. There were no significant differences in clinical characteristics and biochemistry markers (including ghrelin levels) among the different genotypes of Leu72Met. However, plasma ghrelin levels in the GHD group were significantly lower than those of controls (P = 0.001). These results suggest that ghrelin may have a role in GH secretion and controlling growth. Lower ghrelin levels, but not ghrelin/obestatin polymorphism, might contribute to GHD.

  6. Polymorphisms in genes encoding leptin, ghrelin and their receptors in German multiple sclerosis patients.

    PubMed

    Rey, Linda K; Wieczorek, Stefan; Akkad, Denis A; Linker, Ralf A; Chan, Andrew; Hoffjan, Sabine

    2011-01-01

    Multiple sclerosis (MS) is a neuro-inflammatory, autoimmune disease influenced by environmental and polygenic components. There is growing evidence that the peptide hormone leptin, known to regulate energy homeostasis, as well as its antagonist ghrelin play an important role in inflammatory processes in autoimmune diseases, including MS. Recently, single nucleotide polymorphisms (SNPs) in the genes encoding leptin, ghrelin and their receptors were evaluated, amongst others, in Wegener's granulomatosis and Churg-Strauss syndrome. The Lys656Asn SNP in