Bio-X Center, Shanghai Jiao Tong University, Central Little White House, Shanghai, People's Republic of China.
Hum Genet. 2010 Apr;127(4):373-81. doi: 10.1007/s00439-009-0783-x. Epub 2010 Jan 5.
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.
一些关联研究已经探讨了一氧化氮合酶 3 (NOS3) 基因在糖尿病肾病 (DN) 发展中的作用。然而，结果尚无定论，主要是因为这些研究集中在各种不同的多态性上，产生了不一致的结果。我们对 28 项关于 NOS3 基因三个多态性（G894T（Glu289Asp）、4b/a 和 T-786C）与 DN 风险的关联研究进行了荟萃分析，这些研究于 2009 年 7 月前发表，共涵盖了 10364 名受试者。尽管在对 G894T 的分析中最初发现了显著的异质性，但当按种族亚组进行分析时，这种异质性并不存在。894T 与欧洲裔白种人 DN 呈负相关（OR = 0.896，0.817-0.983，95%CI），但与东亚（OR = 2.02，1.20-3.42，95%CI）和其他人群的 DN 呈正相关。当排除涉及微量白蛋白尿的研究时，观察到 4b/a 变异的关联（OR = 1.19，1.02-1.39，95%CI）。T-786C 变异与总体弱关联（OR = 1.16，1.01-1.34，95%CI），异质性较小。总之，我们对 NOS3 基因多态性对 DN 风险影响的荟萃分析支持 NOS3 基因参与 DN 的发病机制。
