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

Background. Nitric oxide is a very potent regulator of intrarenal haemodyna mics and is thought to be an important factor in the deterioration of renal function. Our study sought to verify the hypothesis that endothelial nitri c oxide synthase (ecNOS) gene polymorphism in intron 4 might have some rele vance to progression in chronic renal failure. Methods. We studied the frequencies of gene polymorphism of ecNOS intron 4 in patients with endstage renal disease (302 cases) and compared it with th at of healthy subjects (248 cases). ecNOS genotypes were determined by the polymerase chain reaction, followed by agarose gel electrophoresis. Results. 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), 1.7% (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 n ephropathy (DM group) respectively. The frequency of the ecNOS4a (ecNOSb/a, and ecNOSa/a) in all the patients and in the non-DM group were significant ly 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 ecNO S genotypes between the DM group and the control group (P=0.81). Conclusion. Among the frequencies of ecNOS intron 4 gene polymorphism, a al lele displayed a significantly higher frequency in cases with end-stage ren al failure (ESRF) not caused by diabetic nephropathy. ecNOS gene polymorphi sm in intron 4 appears, therefore, to affect the progression of renal failu re in non- diabetic renal diseases, but the same conclusion could not be dr awn in diabetic nephropathy.