Supplementary Material for: The Endothelial Nitric Oxide Synthase Gene Is Associated with Coronary Artery Disease: A Meta-Analysis

<i>Introduction:</i> Previous case-control studies have suggested that the endothelial nitric oxide synthase <i>(eNOS)</i> gene polymorphisms (G894T, 4b/a, T-786C) are associated with coronary artery disease (CAD). However, other studies do not confirm these relationships. The objective was to assess these relationships using meta-analysis. <i>Methods:</i> Databases, including Pubmed and Embase, were searched to access the relevant genetic association studies up to July 2009. <i>Results:</i> The meta-analysis included 56 studies, consisting of 23 studies for G894T, 19 for 4b/a and 14 for T-786C. For the allelic analysis of the G894T variant, all studies showed a positively significant association (OR = 0.83, p = 0.004). For the genotypic analysis, the combined studies of the T allele showed significance (OR = 1.57, p = 0.003). For the allelic analysis of the T-786C variant, all studies showed an obviously significant association (OR = 0.79, p = 0.0007), reflected in both non-Asian and Asian studies. For the genotype analysis, combined studies of the C allele showed significance (OR = 0.72, p = 0.0001). Moreover, non-Asian studies showed significant results. For the analysis of the 4b/a variant, none of the studies showed significant results. No publication bias was found in the meta-analysis. <i>Conclusion:</i> The synthesis of available evidence supports the fact that <i>eNOS</i> G894T andT-786C are associated with CAD.

<i>引言：</i> 既往病例对照研究表明，内皮型一氧化氮合酶（endothelial nitric oxide synthase, eNOS）基因多态性（G894T、4b/a、T-786C）与冠状动脉粥样硬化性心脏病（coronary artery disease, CAD）存在关联，但另有部分研究未能证实上述关联。本研究旨在通过荟萃分析评估上述关联。<i>方法：</i> 检索PubMed及Embase等数据库，获取截至2009年7月的相关遗传关联研究文献。<i>结果：</i> 本次荟萃分析共纳入56项研究，其中G894T位点相关研究23项、4b/a位点相关研究19项、T-786C位点相关研究14项。针对G894T变异的等位基因分析显示，所有研究均呈现显著正相关（比值比OR=0.83，P=0.004）；基因型分析中，携带T等位基因的合并分析结果具有统计学意义（OR=1.57，P=0.003）。针对T-786C变异的等位基因分析显示，所有研究均呈现显著正相关（OR=0.79，P=0.0007），该结果在非亚洲人群及亚洲人群亚组分析中均得到验证。基因型分析中，携带C等位基因的合并分析结果具有统计学意义（OR=0.72，P=0.0001），且该结果在非亚洲人群亚组中同样显著。针对4b/a变异的分析则未发现任何具有统计学意义的关联。本次荟萃分析未检出发表偏倚。<i>结论：</i> 现有证据综合表明，eNOS基因G894T及T-786C多态性与冠状动脉粥样硬化性心脏病存在关联。