Effects of endothelial nitric oxide synthase gene on end stage renal disease progression in autosomal dominant polycystic kidney disease

AimTo investigate whether endothelial nitric oxide synthase (eNOS) gene associate with the progression of autosomal dominant polycystic kidney disease (ADPKD). MethodsDatabases 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. ResultsA 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. ConclusionsGG 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. Summary at a Glance The genetic mechanisms that underlie the variability in disease phenotype in ADPKD are not entirely clear. In this study, the authors undertake a meta-analysis of published studies on the role of variants of the nitric oxide synthase gene on disease progression.