Impact of Nitric Oxide Synthase Glu298Asp Polymorphism on the Development of End-Stage Renal Disease in Type 2 Diabetic Egyptian Patients

Abstract

Background: Nitric oxide is an important regulator of renal hemodynamics. This study aimed to investigate the role of endothelial nitric oxide synthase (eNOS) gene polymorphism in type 2 diabetic patients with end-stage renal disease (ESRD) and to elucidate any alteration of nitric oxide synthase (NOS) activity caused by this polymorphism. Methods: The study included 80 patients with type 2 diabetes of >10 years duration (40 with diabetes-derived ESRD, 40 without nephropathy) and 20 healthy controls. Plasma nitrate/nitrite level, and serum NOS activity were measured and eNOS Glu298Asp genotypes were determined. Results: The frequency of Glu/Glu (GG) genotype in diabetics with ESRD was lower than controls. However, the frequency of Asp/Asp (TT) genotype was increased in diabetics with ESRD as compared to those without nephropathy and controls. Diabetics with ESRD had significantly lower nitrate/nitrite level and NOS activity than those without nephropathy. Diabetic patients with TT genotype are at a significant risk for ESRD. Moreover, subjects carrying TT genotype had lower nitrate/nitrite level and NOS activity than those carrying GG genotype. In diabetics with ESRD, creatinine clearance was positively correlated with both nitrate/nitrite level and NOS activity. Conclusions: These results imply that TT genotype of eNOS may be associated with an increased risk of ESRD in Egyptian type 2 diabetics. It could represent a useful genetic marker to identify diabetics at high risk for the development of ESRD. However, larger future prospective studies are required to confirm the role of eNOS gene polymorphism in the progression of diabetic nephropathy to ESRD.