Pereira Tiago V, Kimura Lilian, Suwazono Yasushi, Nakagawa Hideaki, Daimon Makoto, Oizumi Toshihide, Kayama Takamasa, Kato Takeo, Li Liao, Chen Shufeng, Gu Dongfeng, Renner Wilfried, März Winfried, Yamada Yoshiji, Bagos Pantelis G, Mingroni-Netto Regina C
Health Technology Assessment Unit, Institute of Education and Health Sciences, German Hospital Oswaldo Cruz, São Paulo, Brazil,
Mol Biol Rep. 2014 May;41(5):3113-25. doi: 10.1007/s11033-014-3171-0. Epub 2014 Jan 30.
The objective of the present study was to review previous investigations on the association of haplotypes in the G-protein β3 subunit (GNB3) gene with representative cardiovascular risk factors/phenotypes: hypertension, overweight, and variation in the systolic and diastolic blood pressures (SBP and DBP, respectively) and as well as body mass index (BMI). A comprehensive literature search was undertaken in Pubmed, Web of Science, EMBASE, Biological Abstracts, LILACS and Google Scholar to identify potentially relevant articles published up to April 2011. Six genetic association studies encompassing 16,068 participants were identified. Individual participant data were obtained for all studies. The three most investigated GNB3 polymorphisms (G-350A, C825T and C1429T) were considered. Expectation-maximization and generalized linear models were employed to estimate haplotypic effects from data with uncertain phase while adjusting for covariates. Study-specific results were combined through a random-effects multivariate meta-analysis. After carefully adjustments for relevant confounding factors, our analysis failed to support a role for GNB3 haplotypes in any of the investigated phenotypes. Sensitivity analyses excluding studies violating Hardy-Weinberg expectations, considering gender-specific effects or more extreme phenotypes (e.g. obesity only) as well as a fixed-effects "pooled" analysis also did not disclose a significant influence of GNB3 haplotypes on cardiovascular phenotypes. We conclude that the previous cumulative evidence does not support the proposal that haplotypes formed by common GNB3 polymorphisms might contribute either to the development of hypertension and obesity, or to the variation in the SBP, DBP and BMI.
本研究的目的是回顾先前关于G蛋白β3亚基（GNB3）基因单倍型与代表性心血管危险因素/表型之间关联的调查：高血压、超重、收缩压和舒张压（分别为SBP和DBP）的变化以及体重指数（BMI）。在PubMed、科学网、EMBASE、生物学文摘、拉丁美洲和加勒比卫生科学数据库以及谷歌学术上进行了全面的文献检索，以识别截至2011年4月发表的潜在相关文章。确定了六项涉及16068名参与者的基因关联研究。获取了所有研究的个体参与者数据。考虑了研究最多的三种GNB3多态性（G-350A、C825T和C1429T）。采用期望最大化和广义线性模型从相位不确定的数据中估计单倍型效应，同时调整协变量。通过随机效应多变量荟萃分析合并研究特异性结果。在仔细调整相关混杂因素后，我们的分析未能支持GNB3单倍型在任何所研究表型中的作用。排除违反哈迪-温伯格期望的研究、考虑性别特异性效应或更极端表型（如仅肥胖）的敏感性分析以及固定效应“合并”分析也未揭示GNB3单倍型对心血管表型有显著影响。我们得出结论，先前的累积证据不支持以下提议，即由常见GNB3多态性形成的单倍型可能导致高血压和肥胖的发生，或导致SBP、DBP和BMI的变化。
