An updated meta-analysis of endothelial nitric oxide synthase gene: three well-characterized polymorphisms with hypertension.
An updated meta-analysis of endothelial nitric oxide synthase gene: three well-characterized polymorphisms with hypertension.
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DOI：
10.1371/journal.pone.0024266
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Qi Y
中科院分区：
文献类型：
--
作者：
Niu W;Qi Y
许多单独的不足关联研究已经进行了内皮型一氧化氮合酶（eNOS）的遗传变异在不同的种族人群，然而，结果往往是不可重复的。因此，我们的目的是荟萃分析三个eNOS广泛评估的多态性，外显子7中的G894 T（rs 1799983），内含子4中的4 b/a和启动子区域中的T-786 C（rs 2070744），与高血压相关的英文和中文出版物，同时解决研究间异质性和出版偏倚。采用Stata软件（11.0版）进行数据分析，采用随机效应模型，不考虑研究间异质性，通过亚组和荟萃回归分析进行评价。使用Egger检验和漏斗图衡量发表偏倚。G894 T多态性的病例/对照总数为19284/26003，4 b/a多态性的病例/对照总数为6890/6858，T− 786 C多态性的病例/对照总数为5346/6392。在所有研究人群中，等位基因894 T与894 G的总体比较显示高血压风险增加16%（比值比[OR]= 1.16; 95%置信区间[95% CI]：1.07-1.27; P = 0.001），尤其是亚洲人风险增加32%（95% CI：1.16-1.52; P<0.0005），中国人风险增加40%（95% CI：1.19-1.65; P<0.0005）。 进一步的亚组分析表明，已发表的语言解释了G894 T多态性的异质性。在所有研究人群中，等位基因4a对4 b的总体OR为1.29（95%CI：1.13-1.46; P<0.0005），亚洲人的估计值更高（OR = 1.42; 95%CI：1.16-1.72; P<0.0005）。 对于T− 786 C，种族分层分析表明白人中− 786 C等位基因（OR = 1.25; 95%CI：1.06-1.47; P = 0.007）和− 786 CC基因型（OR = 1.69; 95%CI：1.20-2.38; P = 0.003）的风险显著增加。 另外，上述风险估计在Bonferroni校正后达到显著性。最后，对其他研究水平协变量的荟萃回归分析未能为所有多态性提供任何意义。我们通过一项综合的荟萃分析，确定了eNOS G894 T和4 b/a多态性在亚洲人高血压中的作用，以及T-786 C多态性在白人中的作用。
Numerous individually underpowered association studies have been conducted on endothelial nitric oxide synthase (eNOS) genetic variants across different ethnic populations, however, the results are often irreproducible. We therefore aimed to meta-analyze three eNOS widely-evaluated polymorphisms, G894T (rs1799983) in exon 7, 4b/a in intron 4, and T−786C (rs2070744) in promoter region, in association with hypertension from both English and Chinese publications, while addressing between-study heterogeneity and publication bias. Data were analyzed using Stata software (version 11.0), and random-effects model was applied irrespective of between-study heterogeneity, which was evaluated by subgroup and meta-regression analyses. Publication bias was weighed using the Egger's test and funnel plot. There were total 19284/26003 cases/controls for G894T, and 6890/6858 for 4b/a, and 5346/6392 for T−786C polymorphism. Overall comparison of allele 894T with 894G in all study populations yielded a 16% increased risk for hypertension (odds ratio [OR] = 1.16; 95% confidence interval [95% CI]: 1.07–1.27; P = 0.001), and particularly a 32% increased risk (95% CI: 1.16–1.52; P<0.0005) in Asians and a 40% increased risk (95% CI: 1.19–1.65; P<0.0005) in Chinese. Further subgroup analyses suggested that published languages accounted for the heterogeneity for G894T polymorphism. The overall OR of allele 4a versus 4b was 1.29 (95% CI: 1.13–1.46; P<0.0005) in all study populations, and this estimate was potentiated in Asians (OR = 1.42; 95% CI: 1.16–1.72; P<0.0005). For T−786C, ethnicity-stratified analyses suggested a significantly increased risk for −786C allele (OR = 1.25; 95% CI: 1.06–1.47; P = 0.007) and −786CC genotype (OR = 1.69; 95% CI: 1.20–2.38; P = 0.003) in Whites. As an aside, the aforementioned risk estimates reached significance after Bonferroni correction. Finally, meta-regression analysis on other study-level covariates failed to provide any significance for all polymorphisms. We, via a comprehensive meta-analysis, ascertained the role of eNOS G894T and 4b/a polymorphisms on hypertension in Asians, and T−786C polymorphism in Whites.
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