title: Effects of endothelial nitric oxide synthase gene on end stage renal disease progression in autosomal dominant polycystic kidney disease.
abstract: OBJECTIVE
  To investigate whether endothelial nitric oxide synthase (eNOS) gene associate with the progression of autosomal dominant polycystic kidney disease (ADPKD).
  
  
  METHODS
  Databases of EMBASE, Pubmed, ISI, Ovid Database, Cochrane library and China National Knowledge Infrastructure were all searched. Associated studies about eNOS polymorphisms and ADPKD were analyzed by meta-analysis.
  
  
  RESULTS
  A total of 11 studies with Glu298Asp and 4b/a polymorphisms were included. A allele of the 4b/a polymorphism increased the risk of end stage renal disease (ESRD) in ADPKD (odds ratio (OR) = 1.85, 95% confidence interval (CI) 1.17-2.94, P = 0.009). However, GG phenotype of Glu298Asp polymorphism neither decreased the ESRD risk (OR = 0.77, 95% CI 0.55-1.08, P = 0.13) nor affected the hypertension risk (OR = 1.04, 95% CI 0.66-1.66, P = 0.86). The GG phenotype carriers had later ESRD age compared with the T allele of Glu298Asp polymorphism (WMD = 2.39; 95% CI 1.32-3.46; P < 0.0001). Significant association was also found in Caucasians (WMD = 2.41; 95% CI 1.18-3.64; P = 0.0001). Subgroup analysis by gender indicated GG genotype carriers had older age of ESRD than T allele carriers in males (WMD = 4.51; 95% CI 3.95-5.08; P = 0.00001), but not in females.
  
  
  CONCLUSIONS
  GG genotype of the Glu298Asp variant slowed the ESRD progression in ADPKD, while a allele carriers of the 4b/a variant increased the risk of ESRD. Variants of eNOS gene might play different roles in the ESRD progression in ADPKD.
authors.affiliation: Department of Nephrology, 252 Hospital of the Chinese People's Liberation Army, Beijing, China; Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Xue
authors.forename: Chen-Chen
authors.initials: CC
authors.lastname: Zhou
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Sun
authors.forename: Liang-Liang
authors.initials: LL
authors.lastname: He
authors.forename: Cheng-Gang
authors.initials: CG
authors.lastname: Xu
authors.forename: Bing
authors.initials: B
authors.lastname: Dai
authors.forename: Chang-Lin
authors.initials: CL
authors.lastname: Mei
mesh_terms: D000328:Adult; D000367:Age Factors; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007676:Kidney Failure, Chronic / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D016017:Odds Ratio; D010641:Phenotype; D016891:Polycystic Kidney, Autosomal Dominant / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012737:Sex Factors; D044465:White People / Q000235:genetics
chemical_list: C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III
keywords: autosomal dominant polycystic kidney disease; endothelial nitric oxide synthase; meta-analysis; polymorphism