State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Mol Biol Rep. 2013 Jun;40(6):4047-53. doi: 10.1007/s11033-012-2482-2. Epub 2012 Dec 28.
The gene encoding β1-adrenoreceptor is regarded as a hypertension-susceptibility candidate gene. The association of β1-adrenoreceptor gene Arg389Gly and Ser49Gly polymorphisms with hypertension has been exhaustively investigated; however, the studies have yielded inconsistent results. We sought to shed some light on this inconsistency by performing a systemic meta-analysis. Data were extracted from 17 articles (cases/controls: 7,586/8,441) for Arg389Gly, and eight articles (3,582/2,998) for Ser49Gly. The random-effects model was applied irrespective of between-study heterogeneity. Overall results indicated significance for Ser49Gly under both allelic (odds ratio = 1.13; 95 % confidence interval [95 % CI] 1.03-1.26; P = 0.011) and dominant (1.19; 1.04-1.28; 0.011) models, without evidence of heterogeneity (I (2) = 0.0 %). Grouping studies by ethnicity observed marginally significant association for Arg389Gly (0.82; 0.66-1.0; 0.049) and Ser49Gly (1.3; 1.0-1.68; 0.048) polymorphisms in Caucasians under allelic model. Association was strikingly potentiated for both polymorphisms after restricting analyses to studies published in English journals. When only large studies (≥500 subjects) were considered, 389Gly allele decreased the odds of developing hypertension by 16 % (0.84; 0.74-0.95; 0.007). There was no observable publication bias for both polymorphisms. Taken together, our results provide clarification to the logical candidacy of β1-adrenoreceptor gene in the development of hypertension.
β1-肾上腺素受体基因被认为是高血压易感性候选基因。β1-肾上腺素受体基因 Arg389Gly 和 Ser49Gly 多态性与高血压的相关性已经被广泛研究;然而,这些研究的结果并不一致。我们试图通过系统的荟萃分析来阐明这种不一致性。从 17 篇文章(病例/对照:7586/8441)中提取 Arg389Gly 的数据,从 8 篇文章(3582/2998)中提取 Ser49Gly 的数据。无论研究间是否存在异质性,均采用随机效应模型进行分析。总体结果表明,Ser49Gly 在等位基因(比值比=1.13;95%置信区间[95%CI]1.03-1.26;P=0.011)和显性(1.19;1.04-1.28;0.011)模型下均具有统计学意义,且无异质性证据(I 2=0.0%)。按种族对研究进行分组后,在等位基因模型下,Arg389Gly (0.82;0.66-1.0;0.049)和 Ser49Gly (1.3;1.0-1.68;0.048)多态性与高加索人群高血压相关,且结果具有边缘统计学意义。限制在英文期刊发表的研究中进行分析后,两种多态性的相关性明显增强。当仅考虑大型研究(≥500 例)时,Arg389Gly 等位基因使发生高血压的风险降低了 16%(0.84;0.74-0.95;0.007)。两种多态性均未观察到明显的发表偏倚。综上所述,我们的结果为β1-肾上腺素受体基因在高血压发生发展中的逻辑候选性提供了明确的证据。