title: Endothelial nitric oxide synthase affects the progression of autosomal dominant polycystic kidney disease.
abstract: OBJECTIVE
  The phenotypic variability of autosomal dominant polycystic kidney disease (ADPKD) cannot be explained only by various mutations of two known genes (PKD1 and PKD2), but the influence of other unknown factors should also be considered. Impairment of endothelial function has been observed in ADPKD patients. Our study tried to verify the hypothesis that endothelial nitric oxide synthase (ecNOS) gene polymorphisms in intron 4 could have some relevance to the progression of ADPKD.
  
  
  METHODS
  We examined 155 Czech patients with ADPKD (80 males, 75 females; mean age 43.4 +/- 14.7 years) and 100 genetically unrelated healthy subjects (50 men, 50 women; mean age 51.2 +/- 8.2 years). The genomic DNA was amplified by polymerase chain reaction and the products were separated on 1.5% agarose gel and visualised by ultraviolet transillumination. We compared subjects homozygous for the ecNOSb allele with subjects homozygous and heterozygous for the ecNOSa allele.
  
  
  RESULTS
  The frequencies of ecNOSb/b, ecNOSa/b and ecNOSa/a were 81% (81/100), 17% (17/100) and 2% (2/100), respectively, in the control group, 60% (30/50), 32% (16/50) and 8% (4/50), respectively, in ADPKD patients with end-stage renal failure (ESRF), and 68.5% (72/105), 28.6% (30/105) and 2.9% (3/105), respectively, in ADPKD patients with normal renal function. The two-tailed t test revealed that the frequency of the ecNOSa allele (ecNOSa/b and ecNOSa/a) in dialysed patients was significantly higher than in ADPKD patients with normal renal function (p < 0.05).
  
  
  CONCLUSIONS
  The a allele of the ecNOS gene polymorphism showed a significantly higher incidence among patients with ESRF caused by ADPKD. The a allele might have a negative influence on the progression of ADPKD.
authors.affiliation: Department of Nephrology, Charles University, Prague, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Reiterová
authors.forename: Miroslav
authors.initials: M
authors.lastname: Merta
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tesar
authors.forename: Jitka
authors.initials: J
authors.lastname: Stekrová
mesh_terms: D000328:Adult; D000483:Alleles; D004247:DNA / Q000235:genetics; D018450:Disease Progression; D004587:Electrophoresis, Agar Gel; D005260:Female; D006801:Humans; D007438:Introns / Q000235:genetics; D007676:Kidney Failure, Chronic / Q000201:enzymology / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III; D010641:Phenotype; D016891:Polycystic Kidney, Autosomal Dominant / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D009569:Nitric Oxide; D004247:DNA; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III