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Nephrology Dialysis Transplantation 2004 19(9):2302-2306; doi:10.1093/ndt/gfh077
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Nephrol Dial Transplant Vol. 19 No. 9 © ERA-EDTA 2004; all rights reserved

Original Article

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

Monika Buraczynska, Piotr Ksiazek, Wojciech Zaluska, Teresa Nowicka and Andrzej Ksiazek

Laboratory for Molecular Diagnostics of Multifactorial Diseases, Department of Nephrology, University Medical School, Lublin, Poland

Correspondence and offprint requests to: Monika Buraczynska, Laboratory for Molecular Diagnostics of Multifactorial Diseases, Department of Nephrology, University Medical School, Dr K. Jaczewskiego 8, 20-954 Lublin, Poland. Email: mjbur{at}asklepios.am.lublin.pl

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.

Keywords: diabetic nephropathy; DNA polymorphism; endothelial nitric oxide synthase; end-stage renal disease; molecular genetics; polymerase chain reaction


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