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

Nephrol Dial Transplant. 2004 Sep;19(9):2302-6. doi: 10.1093/ndt/gfh077.


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.

MeSH terms

  • Case-Control Studies
  • Dialysis
  • Disease Progression
  • Endothelial Cells / physiology*
  • Endothelium, Vascular / physiology*
  • Female
  • Genotype
  • Humans
  • Introns
  • Kidney Failure, Chronic / genetics*
  • Kidney Failure, Chronic / therapy
  • Male
  • Middle Aged
  • Nitric Oxide Synthase / genetics*
  • Polymorphism, Genetic


  • Nitric Oxide Synthase