An Updated Meta-Analysis of Endothelial Nitric Oxide Synthase Gene: Three Well-Characterized Polymorphisms with HypertensionReport as inadecuate




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Background

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.

Methods

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.

Results

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.

Conclusion

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.



Author: Wenquan Niu , Yue Qi

Source: http://plos.srce.hr/



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