No association between NOS2 and NOS3 polymorphisms and diabetic nephropathy in type 2 diabetics

Abstract

Background: Diabetic animal models suggest the involvement of nitric oxide (NO)-producing enzymes in the development of diabetic nephropathy (DN). While early stages of DN are associated with increased intrarenal NO, advanced DN is related to progressive NO deficiency. NO collaborates in reactive nitrogen compounds production, contributing to accelerated oxidative stress. To investigate the impact of genetic polymorphisms of NO-producing enzymes on DN development, we tested 3 polymorphic variants that could affect their function and compared genotype status to an oxidative stress marker. Methodology: 198 Slovenian (Caucasian) type 2 diabetic (T2D) patients, age 34-83, were classified into two groups according to the presence of DN and tested for eNOS Glu298Asp, eNOS 4a/b and iNOS Ser608Leu polymorphisms using PCR and qPCR. Oxidative stress was assessed through serum 8-OHdG level. Results were analyzed using ANOVA, Chi-square test and multivariate logistic regression. Results: We found no association between the selected polymorphisms and DN. However, we found a significant increase in oxidative stress level in iNOS 608Leu/Leu patients. Conclusions: We failed to demonstrate the association between the selected eNOS and iNOS genetic polymorphisms and DN. Our results reflect the multifactorial nature of DN in addition to genetic heterogeneity within and between the populations. © 2012 Versita Warsaw and Springer-Verlag Wien.