title: Endothelial nitric oxide synthase gene variation associated with chronic kidney disease after liver transplant.
abstract: OBJECTIVE
  To identify single nucleotide polymorphisms (SNPs) associated with risk of developing chronic kidney disease (CKD), a prevalent comorbidity, after liver transplant (LT).
  
  
  METHODS
  This study consists of a cohort of adult (> or =18 years) primary-LT recipients who had normal renal function before LT and who survived 1 year or more after LT at a high-volume US LT program between January 1, 1990, and December 31, 2000. Patients with adequate renal function (estimated glomerular filtration rate, > or =40 mL/min per 1.73 m(2) during follow-up; n=308) and patients with incident CKD (estimated glomerular filtration rate, <40 mL/min per 1.73 m(2) after LT; n=92) were identified. To investigate the association of 6 candidate genes with post-LT CKD, we selected SNPs that have been associated with renal function in the literature. Hazard ratios were estimated using Cox regression, adjusted for potential confounding variables.
  
  
  RESULTS
  The variant allele (298Asp) of the Glu298Asp SNP in the endothelial nitric oxide synthase gene (NOS3) was significantly associated with CKD after LT (P=.05; adjusted for multiple comparisons). The 5-year incidence of CKD was 70% among patients homozygous for the NOS3 variant allele (298Asp) compared with 42% among those not homozygous for the NOS3 variant allele. Specifically, homozygosity for the NOS3 variant allele conferred a 2.5-fold increased risk of developing CKD after LT (P=.005, adjusted for confounding variables).
  
  
  CONCLUSIONS
  Homozygosity for the variant allele of NOS3 (298Asp) is associated with CKD after LT and may be useful for identifying recipients at higher risk of post-LT CKD.
authors.affiliation: Division of Gastroenterology and Hepatology, University of Colorado Health Sciences Center, Denver, USA.
authors.forename: Kiran
authors.initials: K
authors.lastname: Bambha
authors.forename: W Ray
authors.initials: WR
authors.lastname: Kim
authors.forename: Charles B
authors.initials: CB
authors.lastname: Rosen
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Pedersen
authors.forename: Cynthia
authors.initials: C
authors.lastname: Rys
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Kolbert
authors.forename: Julie M
authors.initials: JM
authors.lastname: Cunningham
authors.forename: Terry M
authors.initials: TM
authors.lastname: Therneau
mesh_terms: D000483:Alleles; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D005919:Glomerular Filtration Rate; D006720:Homozygote; D006801:Humans; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000235:genetics*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016016:Proportional Hazards Models
chemical_list: C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III
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