Abstract
BackgroundNumerous 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.MethodsData 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.ResultsThere 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.ConclusionWe, 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.
Highlights
Hereditary factors contributed directly to the occurrence of hypertension, as evidenced by family studies showing that premature onset of hypertension among first-degree relatives yielded a remarkable high risk of 3.8 times to develop this disorder [1]
Since the genomic sequence of endothelial nitric oxide synthase (eNOS) is highly polymorphic, it is of added interest to confirm which polymorphism(s) at eNOS might have functional potentials to affect the final bioavailability of eNOS, and the development of
A large panel of individually underpowered studies have been conducted on eNOS polymorphisms across different ethnic populations, yet with irreproducible and inconclusive results
Summary
Hereditary factors contributed directly to the occurrence of hypertension, as evidenced by family studies showing that premature onset of hypertension among first-degree relatives yielded a remarkable high risk of 3.8 times to develop this disorder [1] It remains unclear how many genes or which genetic determinants might constitute such hereditary background [2]. To derive a more precise estimation, we meta-analyzed three eNOS widely-evaluated polymorphisms, G894T (rs1799983) in exon 7, 4b/a (an insertion-deletion with 4a denoting four tandem 27-bp repeats and 4b five repeats) in intron 4, T2786C (rs2070744) in promoter region, in association with hypertension from the English and Chinese-published literature, while addressing between-study heterogeneity and publication bias. We aimed to meta-analyze three eNOS widely-evaluated polymorphisms, G894T (rs1799983) in exon 7, 4b/a in intron 4, and T2786C (rs2070744) in promoter region, in association with hypertension from both English and Chinese publications, while addressing between-study heterogeneity and publication bias
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