Association of Superoxide dismutases (SOD1 and SOD2) and Glutathione peroxidase 1 (GPx1) gene polymorphisms with type 2 diabetes mellitus.

Abstract

Type 2 diabetes mellitus (T2DM) is a metabolic disorder resulting from oxidative stress (OS), the root cause of insulin resistance, β-cell dysfunction, and impaired glucose tolerance. Antioxidant enzymes play key roles in cellular defense and can be used as important biomarkers for T2DM. The present study was undertaken to evaluate three genetic polymorphisms viz. SOD1 + 35A/C, SOD2 + 47C/T, and GPx + 599C/T in 207 T2DM cases and 210 healthy controls from North India. DNA was extracted from blood samples and genotyping was done by PCR-RFLP. Genotypic/allelic frequencies and haplotype/gene-gene interaction analysis were performed using SPSS (version 15.0) and SHEsis (v. online). Except age, all other biochemical parameters showed highly significant association in T2DM cases (P < 0.001). In North Indian population, SOD1 + 35A/C variant was monomorphic. Genotype/allele frequencies of SOD2 + 47C/T polymorphism and carriage rate of 'C' allele showed significant association (p < 0.05, < 0.001; OR 2.434). Genotype/allele frequencies of GPx1 + 599C/T and carriage rate showed no association although the odds ratio of GPx1 'C' allele indicated a 1.362 times higher risk of T2DM. SOD2 'CT' and GPx1 'CC' genotypes showed maximum association with biochemical parameters. Haplotype/gene-gene interaction analysis in controls and cases showed that SOD2 + 47C/T and GPx1 + 599C/T were in linkage disequilibrium (D: 0.168; r(2): 0.10) and individuals with this combination had a 1.273 times higher risk [OR; CI (95%)] of developing T2DM. Thus, we conclude that it is essential to assess the combinatorial association of gene variants with T2DM in order to identify risk haplotypes in a population.