Endothelial nitric oxide synthase polymorphism influences renal allograft outcome

Clin Transplant. 2014 Feb;28(2):223-8. doi: 10.1111/ctr.12302. Epub 2013 Dec 26.

Abstract

Background: Atherosclerotic lesions within the graft are considered to be a major cause of interstitial fibrosis/tubular atrophy (IF/TA). We evaluated the factors that influence the development of IF/TA and three- and five-yr graft survival including nitric oxide synthase (eNOS) and angiotensin II type 1 and type 2 receptor gene polymorphism.

Methods: Seventy-one male and 35 female patients (age: 34.9 ± 11.2 yr) who underwent living-related renal transplantation were included. Angiotensin type 1 and type 2 receptor gene polymorphisms and eNOS intron 4 gene polymorphism were analyzed. The pre- and post-transplant laboratory data, patient characteristics, acute rejection episodes, and presence of IF/TA were evaluated.

Results: Patients with the bb allele of eNOS gene had a lower prevalence of post-transplant third year (12.6% and 38.5%, p = 0.005) and fifth year IF/TA (46.6% and 82.3%, p = 0.02) and a lower incidence of five-yr graft failure (35.4% and 55.6%, p < 0.005). The eNOS gene polymorphism was independent and was the most prominent factor associated with third and fifth year IF/TA (p = 0.01, RR: 29.72, and p = 0.03, RR: 4.1, respectively). No significant relationship existed when angiotensin II gene polymorphisms were considered.

Conclusions: We concluded that recipient eNOS gene polymorphism can predict IF/TA, and the presence of the bb allele is associated with better graft outcome.

Keywords: eNos gene polymorphism; interstitial fibrosis/tubular atrophy; renal transplantation.

MeSH terms

  • Adult
  • Female
  • Follow-Up Studies
  • Genotype
  • Glomerular Filtration Rate
  • Graft Survival / genetics*
  • Humans
  • Kidney Failure, Chronic / genetics*
  • Kidney Failure, Chronic / mortality
  • Kidney Failure, Chronic / surgery
  • Kidney Function Tests
  • Kidney Transplantation*
  • Male
  • Nitric Oxide Synthase Type III / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic / genetics*
  • Postoperative Complications / genetics*
  • Prognosis
  • Receptor, Angiotensin, Type 1 / genetics
  • Receptor, Angiotensin, Type 2 / genetics
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III