title: Genetic association of Glutathione peroxidase-1 (GPx-1) and NAD(P)H:Quinone Oxidoreductase                      1(NQO1) variants and their association of CAD in patients with type-2 diabetes.
abstract: Coronary artery disease (CAD) is a major health concern and the leading cause of death in individuals with type-2 diabetes mellitus (T2DM). Glutathione peroxidase-1 (GPx-1) and NAD(P)H: quinone oxidoreductase (NQO1) are known for its broad range of detoxification. The role of functional variants of these genes in the development of various disorders is proven. Hereby, we investigated the possible role of these variants in the development of CAD in T2DM patients of South Indian population. In this case-control study, a total of 539 patients (T2DM = 241; T2DM-CAD = 298) and 285 controls were included. The C198T GPx-1 and C609T NQO1 single-nucleotide polymorphisms were analyzed by PCR-RFLP. Further, these genotypes were correlated with blood lipid profile. Regression analysis showed that GPx1-C/T genotype is associated with a 1.35-fold increase (95% CI = 1.000-1.824; P = 0.048) and GPx1-T/T genotype is associated with a 1.76-fold increase (95% CI = 1.011 to 3.066; P = 0.046) to the T2DM development. Increased odds ratio showed that NQO1-T/T genotype had a higher occurrence of CAD in diabetic patients with CAD (95% CI = 1.003-2.674, P = 0.049) than T2DM patients without CAD. The level of triglycerides alone showed significant increase for GPx-1-C/T and -T/T genotypes in Tukey's Post hoc analysis (177.1 ± 19.2 vs. 184 ± 23.5; P = 0.039 and 177.1 ± 19.2 vs. 190 ± 22.4; P = 0.006) among the patients with T2DM-CAD. Our work concludes that GPx-1 variants might contribute to the development of diabetes and both GPx-1 and NQO1 variants confirm the association of CAD in people with T2DM of South Indian population.
authors: Department of Biochemistry, Center for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamilnadu, India.
authors: Tharmarajan
authors: T
authors: Ramprasath
authors: Ponniah Senthil
authors: PS
authors: Murugan
authors: Ellappan
authors: E
authors: Kalaiarasan
authors: Pannerselvam
authors: P
authors: Gomathi
authors: Andiappan
authors: A
authors: Rathinavel
authors: Govindan Sadasivam
authors: GS
authors: Selvam
mesh_terms: D000328:Adult; D054458:Amplified Fragment Length Polymorphism Analysis; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000097:blood / Q000201:enzymology* / Q000209:etiology / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000201:enzymology* / Q000235:genetics; D003925:Diabetic Angiopathies / Q000097:blood / Q000201:enzymology* / Q000209:etiology / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005979:Glutathione Peroxidase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007194:India; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics* / Q000378:metabolism; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D000094765:Glutathione Peroxidase GPX1
chemical_list: D008055:Lipids; D005979:Glutathione Peroxidase; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human