Department of Preventive Medicine, Wannan Medical College, 241002 Wuhu, Anhui, China.
Gene. 2013 Oct 10;528(2):84-92. doi: 10.1016/j.gene.2013.06.047. Epub 2013 Jul 9.
Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene may influence the risk of ischemic stroke (IS), but the results are still debatable. A meta-analysis was performed to investigate the association between the eNOS gene polymorphisms in IS risk. Case-control studies on the association between the G894T, T-786C, and 4b/a polymorphisms and IS were searched up to July 2012, and the genotype frequencies in the control group were found to be consistent with the Hardy-Weinberg equilibrium (HWE). The effect summary odds ratio (OR) and 95% confidence intervals (CIs) were obtained. Meta-regression was used to explore the potential sources of heterogeneity. Funnel plots and Egger's test was used to estimate small study biases, and heterogeneity was assessed by chi-square-based Q-test and I(2) test. There were total 6537/6475 cases/controls for G894T, 3459/3951 cases/controls for 4b/a, and 2125/2673 cases/controls for T-786C polymorphism. For G894T and 4b/a, a significant association of 894T allele and 4a allele with increased risk of IS was found in Asians (TT+GT vs. GG: p<0.00001, OR=1.60, 95% CI=1.38-1.79, Pheterogeneity=0.11; aa+ba vs. bb: P<0.00001, OR=1.60, 95% CI=1.30-1.97, Pheterogeneity=0.02), but not in Caucasians (TT+GT vs. GG: P=0.60, OR=0.94, 95% CI=0.75-1.19, Pheterogeneity=0.002; aa+ba vs. bb: P=0.13, OR=0.81, 95% CI=0.62-1.06, Pheterogeneity=0.63). For T-786C polymorphism, there were no significant differences in genotype distribution between IS and control in Asians (CC+TC vs. TT: P=0.15, OR=1.14, 95% CI=0.95-1.37, Pheterogeneity=0.94) and in Caucasians (CC+TC vs. TT: P=0.72, OR=0.96, 95% CI=0.75-1.22, Pheterogeneity=0.53). This analysis provides strong evidence that the eNOS T-786C gene polymorphism is not associated with IS, the G894T and 4b/a polymorphisms might be associated with IS, at least in Asians.
内皮型一氧化氮合酶（eNOS）基因多态性可能影响缺血性脑卒中（IS）的风险，但结果仍存在争议。进行了一项荟萃分析，以调查 eNOS 基因多态性与 IS 风险之间的关联。截至 2012 年 7 月，检索了与 G894T、T-786C 和 4b/a 多态性与 IS 相关的病例对照研究，并发现对照组的基因型频率符合 Hardy-Weinberg 平衡（HWE）。获得了效应汇总比值比（OR）和 95%置信区间（CI）。采用元回归来探讨潜在的异质性来源。漏斗图和 Egger 检验用于估计小样本研究偏倚，采用基于卡方的 Q 检验和 I(2)检验评估异质性。G894T 有 6537/6475 例/对照，4b/a 有 3459/3951 例/对照，T-786C 有 2125/2673 例/对照。对于 G894T 和 4b/a，在亚洲人群中，894T 等位基因和 4a 等位基因与 IS 风险增加显著相关（TT+GT 与 GG：P<0.00001，OR=1.60，95%CI=1.38-1.79，P 异质性=0.11；aa+ba 与 bb：P<0.00001，OR=1.60，95%CI=1.30-1.97，P 异质性=0.02），但在白种人群中则没有（TT+GT 与 GG：P=0.60，OR=0.94，95%CI=0.75-1.19，P 异质性=0.002；aa+ba 与 bb：P=0.13，OR=0.81，95%CI=0.62-1.06，P 异质性=0.63）。对于 T-786C 多态性，在亚洲人群（CC+TC 与 TT：P=0.15，OR=1.14，95%CI=0.95-1.37，P 异质性=0.94）和白种人群（CC+TC 与 TT：P=0.72，OR=0.96，95%CI=0.75-1.22，P 异质性=0.53）中，IS 与对照组之间的基因型分布没有显著差异。这项分析提供了有力的证据表明，内皮型一氧化氮合酶 T-786C 基因多态性与 IS 无关，G894T 和 4b/a 多态性可能与 IS 相关，至少在亚洲人群中如此。
