Endothelial nitric oxide synthase gene polymorphism in intron 4 affects the progression of renal failure in non-diabetic renal diseases.

Abstract

Nitric oxide is a very potent regulator of intrarenal haemodynamics and is thought to be an important factor in the deterioration of renal function. Our study sought to verify the hypothesis that endothelial nitric oxide synthase (ecNOS) gene polymorphism in intron 4 might have some relevance to progression in chronic renal failure. We studied the frequencies of gene polymorphism of ecNOS intron 4 in patients with end-stage renal disease (302 cases) and compared it with that of healthy subjects (248 cases). ecNOS genotypes were determined by the polymerase chain reaction, followed by agarose gel electrophoresis. Two alleles of ecNOS intron 4, labelled a and b could be detected; a has four and b has five tandem 27-bp repeats. The frequencies of ecNOS4b/b, ecNOS4b/a, ecNOS4a/a genotypes were 81.0% (201/248), 19. 0% (47/248), 0.0% (0/248) in the control group, and 74.8% (226/302), 23.5% (71/302), l.7% (5/302) in all the patients, 72.7% (168/231), 25.1% (58/231), 2.2% (5/231) in the group with end-stage renal diseases, excluding diabetic nephropathy (non-DM group), and 81.7% (58/71), 18.3% (13/71), 0.0% (0/71) in diabetic nephropathy (DM group) respectively. The frequency of the ecNOS4a (ecNOSb/a, and ecNOSa/a) in all the patients and in the non-DM group were significantly higher than that in the control group (P=0.021; P=0. 0096 respectively). In contrast, there was no significant difference in the frequencies of ecNOS genotypes between the DM group and the control group (P=0.81). Among the frequencies of ecNOS intron 4 gene polymorphism, a allele displayed a significantly higher frequency in cases with end-stage renal failure (ESRF) not caused by diabetic nephropathy. ecNOS gene polymorphism in intron 4 appears, therefore, to affect the progression of renal failure in non- diabetic renal diseases, but the same conclusion could not be drawn in diabetic nephropathy.