title: A meta-analysis of three polymorphisms in the endothelial nitric oxide synthase gene (NOS3) and their effect on the risk of diabetic nephropathy.
abstract: A number of association studies have investigated the role of the nitric oxide synthase 3 (NOS3) gene in the development of diabetic nephropathy (DN). However, results have been inconclusive, largely because the studies have focused on a variety of different polymorphisms and generate inconsistent results. We performed a meta-analysis of 28 association studies focusing on three polymorphisms in the NOS3 gene (G894T (Glu289Asp), 4b/a, and T-786C) and the risk of DN published before July 2009, covering a total of 10,364 subjects. Although significant heterogeneity was initially found in the analysis of G894T, it did not remain when analysis was done by ethnic subgroups. 894T was negatively associated with DN in Caucasian populations of European origin (OR = 0.896, 0.817-0.983, 95% CI), but was positively associated with DN in East Asian (OR = 2.02, 1.20-3.42, 95% CI) and other populations. Association of the 4b/a variant was observed when studies involving microalbuminuria were excluded (OR = 1.19, 1.02-1.39, 95% CI). The T-786C variant showed an overall weak association (OR = 1.16, 1.01-1.34, 95% CI) with little heterogeneity. In summary, our meta-analysis of the effect of NOS3 gene polymorphisms on the risk of DN supports the involvement of the NOS3 gene in the pathogenesis of DN.
authors.affiliation: Bio-X Center, Shanghai Jiao Tong University, Central Little White House, Shanghai, People's Republic of China. zzhen@sjtu.edu.cn
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zeng
authors.forename: Lina
authors.initials: L
authors.lastname: Li
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Wei
authors.forename: Ke
authors.initials: K
authors.lastname: Huang
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.forename: Yongyong
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D003928:Diabetic Nephropathies / Q000201:enzymology* / Q000235:genetics*; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III