Polymorphisms in oxidative stress pathway genes and risk of diabetic nephropathy in South Indian type 2 diabetic patients

Abstract

Aim: Diabetic nephropathy (DN), a common microvascular complication of type 2 diabetes mellitus (T2DM) is polygenic, with a vast array of genes contributing to disease susceptibility. Accordingly, we explored the association between DN and six polymorphisms in oxidative stress related genes, namely eNOS, p22phox subunit of NAD(P)H oxidase, PARP-1 and XRCC1 in South Indian T2DM subjects.

Methods: The study included 155 T2DM subjects with DN and 162 T2DM patients with no evidence of DN. The selected polymorphisms were genotyped by polymerase chain reaction and Taqman allele discrimination assay.

Results: No significant difference was observed in the genotype and allele distribution of eNOS -786T > C, intron 4a4b, p22phox 242C > T and XRCC1 Arg399Gln polymorphisms between T2DM groups with and without DN. Contrastingly, there appeared to be a significant association of eNOS 894G > T and PARP-1 Val762Ala polymorphisms with DN wherein, the presence of 894T allele was associated with an enhanced risk for DN [P = 0.005; OR = 1.78 (1.17-2.7)], while the 762Ala allele seemed to confer significant protection against DN [P = 0.02; OR = 0.59 (0.37-0.92)]. Multiple logistic regression analysis revealed a significant and independent association of eNOS 894G > T, PARP-1 Val762Ala polymorphisms and hypertension with DN in T2DM individuals.

Conclusions: eNOS 894G > T and PARP-1 Val762Ala polymorphisms appeared to associate significantly with DN, with the former contributing to an enhanced risk and the latter to a reduced susceptibility to DN in South Indian T2DM individuals.

Keywords: diabetic nephropathy; oxidative stress; polymorphism; type 2 diabetes mellitus.