Oxidative stress and not endothelial nitric oxide synthase gene polymorphism involved in diabetic nephropathy

Abstract

Diabetic Nephropathy (DN) poses a major health problem. There is strong evidence for a potential role of the eNOS gene. The aim of this case control study was to investigate the possible role of genetic variants of the endothelial Nitric Oxide Synthase (eNOS) gene and oxidative stress in the pathogenesis of nephropathy in patients with diabetes mellitus. The study included 124 diabetic patients; 68 of these patients had no diabetic nephropathy (group 1) while 56 patients exhibited symptoms of diabetic nephropathy (group 2). Sixty two healthy non-diabetic individuals were also included as a control group. Blood samples from subjects and controls were analyzed to investigate the eNOS genotypes and to estimate the lipid profile and markers of oxidative stress such as malondialdehyde (MDA) and nitric oxide (NO). No significant differences were found in the frequency of eNOS genotypes between diabetic patients (either in group 1 or group 2) and controls (p >0.05). Also, no significant differences were found in the frequency of eNOS genotypes between group 1 and group 2 (p >0.05). Both group 1 and group had significantly higher levels of nitrite and MDA when compared with controls (all p = 0.0001). Also group 2 patients had significantly higher levels of nitrite and MDA when compared with group 1 (p = 0.02, p = 0.001 respectively). The higher serum level of the markers of oxidative stress in diabetic patients particularly those with diabetic nephropathy suggest that oxidative stress and not the eNOS gene polymorphism is involved in the pathogenesis of the diabetic nephropathy in this subset of patients. Key words: eNOS polymorphism, oxidative stress, diabetic nephropathy.