Key result
Carriage of the ecNOS4a allele was significantly associated with an increased risk of end-stage renal disease compared to healthy controls (OR 1.95; 95% CI 1.13-3.4; P=0.0031).
Why the study?
Is the ecNOS4 gene polymorphism associated with an increased risk of end-stage renal disease?
Case-Control (n=1,027)
Is the ecNOS4 gene polymorphism associated with an increased risk of end-stage renal disease?
Odds Ratio: 1.95 (95% CI 1.13–3.4)
Absolute Event Rate: 41.5% vs 26%
p-value: p=0.0031
The ecNOS4a allele is associated with an increased risk of chronic renal failure, suggesting a genetic predisposition related to endothelial nitric oxide synthase.
ecNOS4a carriage may flag elevated ESRD susceptibility; leaves open replication and clinical utility of genotyping.
BACKGROUND: 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 cardiovascular and renal diseases. We investigated a potential involvement of this polymorphism in chronic renal failure. METHODS: We performed a case-control study involving 706 patients with end-stage renal disease (ESRD) and 321 healthy controls. All subjects were genotyped for the ecNOS4 polymorphism by the polymerase chain reaction followed by agarose gel electrophoresis. RESULTS: The analysis revealed that the frequencies of the ecNOS4 genotypes were significantly different in ESRD patients, both diabetic and non-diabetic, than in controls. In all dialysis patients for aa, ab and bb genotypes the frequencies were, respectively, 6.5, 35 and 58.5% in the patient group, and 1, 25 and 74% in control subjects. The a allele carriers (aa + ab) were more frequent among ESRD patients than in controls (OR 1.95; 95% CI 1.13-3.4; P = 0.0031). No significant association was found when hypertensive ESRD patients were compared with normotensive patients. The distribution of genotypes was similar in both subgroups (P = 0.21). CONCLUSION: There was a significantly higher frequency of the ecNOS4a allele carriers among ESRD patients, both diabetic and non-diabetic, than in control subjects. This suggests that the ecNOS gene polymorphism may be associated with an increased risk of chronic renal failure.
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Buraczyńska et al. (2004) conducted a case-control in End-stage renal disease (ESRD) (n=1,027). ecNOS4a allele carrier status (aa + ab genotypes) vs. Healthy controls was evaluated on Presence of end-stage renal disease (OR 1.95, 95% CI 1.13-3.4, p=0.0031). Carriage of the ecNOS4a allele was significantly associated with an increased risk of end-stage renal disease compared to healthy controls (OR 1.95; 95% CI 1.13-3.4; P=0.0031).
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