endothelial nitric oxide synthase gene intron 4 polymorphism in Egyptian patients with end-stage renal disease

ABSTRACT

Nitric oxide [NO] synthesized by endothelial cell NO synthase [ecNOS] is a potent regulator of intrarenal haemodynamics. A polymorphism in intron 4 of the ecNOS gene is a candidate gene in renal diseases. The aim of this work is to study the gene polymorphism of ecNOS intron 4 in patients with end-stage renal failure and compared it with that of healthy subjects. The study was performed on 40 patients with end stage renal disease [ESRD] patients on regular hemodialysis, and was classified into 2 groups Group I ESRD patients with diabetic nephropathy [10 patients] and group II includes 30 patients with ESRD due to different etiologies [all causes except diabetic nephropathy], and group III 15 apparently healthy subjects as control group. ecNOS genotypes were determined using polymerase chain reaction. The results showed that two alleles of ecNOS intron 4, labeled a and b could be detected. The frequencies of aa, ba, bb genotypes were 5% [2/40], 12.5% [5/40] 82.5% [33/40] in all the patients, 3.3% [1/30], 13.3% [4/30], 83.3% [25/30] in-group II patients, and 10% [1/10], 10% [1/10] 80% [8/10] in group I patients respectively, and in the control group all were bb100% [15/15]. There is significant difference in the frequencies of ecNOS genotypes between all ESRD patients and the control group [OR 1.423; 95% CI 1.253-1.615, p<0.01]. Compared with controls; the group I patients had much higher frequency of the ecNOS 4a allele than in-group II patients [OR 2.765, 1.556, 95% CI 1.891-4.042, 1.423-1.615, p<0.001, p<0.01] respectively. There was a significantly higher frequency of the ecNOS 4a allele among ESRD patients both diabetic and non-diabetic than in control subjects. This suggests that the ecNOS gene polymorphism in intron 4 appears to be prognostic of renal failure and the ecNOS gene polymorphism in intron 4 is a useful parameter for studying the relationship between NO and the progression of renal failure. This suggests that the ecNOS gene polymorphism might be associated with an increased risk of chronic renal failure