Polymorphisms in oxidative stress pathway genes and risk of diabetic nephropathy in S outh I ndian type 2 diabetic patients

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 S outh I ndian 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 T aqman allele discrimination assay. Results No significant difference was observed in the genotype and allele distribution of eNOS −786T> C , intron 4a4b, p22phox 242 C > T and XRCC1 Arg399Gln polymorphisms between T2DM groups with and without DN . Contrastingly, there appeared to be a significant association of eNOS 894 G > T and PARP ‐1 V al762Ala polymorphisms with DN wherein, the presence of 894 T allele was associated with an enhanced risk for DN [ P  = 0.005; OR  = 1.78 (1.17–2.7)], while the 762 A la 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 894 G > T , PARP ‐1 Val762Ala polymorphisms and hypertension with DN in T2DM individuals. Conclusions eNOS 894 G > 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 S outh I ndian T2DM individuals.