Endothelial Nitric Oxide Synthase Gene Polymorphism and the Risk of Diabetic Neuropathy in Asian Indian Patients with Type 2 Diabetes

Endothelial dysfunction plays a key role in the pathogenesis of diabetic vascular disease, including diabetic neuropathy (DNP). Endothelial-derived nitric oxide synthase (eNOS) gene polymorphisms affect eNOS activity and are associated with endothelial dysfunction. Studies examining association of eNOS gene polymorphism in type 2 diabetic patients (T2DM) with DNP and without DNP are lacking in Asian Indians. Thus, we investigated the association and interaction between two potentially functional single nucleotide polymorphisms (SNPs) of the eNOS gene (T-786C, G894T) and one repeat polymorphism (27VNTR) with DNP using validated PCR-RFLP assays in 1258 T2DM subjects belonging to two independent cohorts from north Indian Origin and also, we replicated our study in a 3 rd independent cohort from south Indian population having T2DM. We also measured serum Nitric Oxide (NO) levels in these subjects and examined its correlation with DNP and eNOS genotypes. We observed that eNOS genotype carrying 'aa' genotype of 27VNTR (a/b) and eNOS haplotype C-a-G and C-a-T (allele of T-786C, 27VNTR a/b and G894T) carrying 'a' allele of 27VNTR (a/b) were associated with increased risk of DNP, in all the three cohorts. We also observed lower serum NO levels in T2DM subjects (both cases and controls) carrying ba+aa genotypes. Our study suggest that 27VNTR (a/b) eNOS polymorphism carrying 'a' allele alone and in association with T-786C and G894T eNOS polymorphism is associated with increased risk of DNP in Asian Indians T2DM patients.