Yang Hualing, Cai Dongmiao, Zhu Qingping, Wu Dongjin, Wang Qingxiang, Wang Zhanxiang
Department of Anesthesiology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China.
The First Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China.
Oncotarget. 2017 Jul 11;8(28):46480-46490. doi: 10.18632/oncotarget.16666.
This meta-analysis was implemented to test the association of a missense mutation, Trp64Arg, in β3-adrenoreceptor-encoding gene (ADRB3) with both hypertension risk and blood pressure (BP) changes. A systematic search of three publicly-available databases was launched to look for articles published as of December 2016. Qualification appraisal and data extraction were independently done by two researchers. Pooled estimates were expressed as odds ratio (OR) or weighted mean difference (WMD), and their 95% confidence intervals (95% CIs). There were separately 21 (3750/4225 patients/controls) and 17 (6100 subjects) individual studies for hypertension risk and BP changes. Integral analyses revealed that Trp64Arg mutation was associated with the significantly increased risk of hypertension, and particularly, the 64Trp/64Arg heterozygote carriers were 1.23-times more likely to develop hypertension compared with the 64Trp/64Trp homozygote carriers (OR = 1.23, 95% CI: 1.021.46, P = 0.021). Publication bias was extremely low for all integral comparisons. In stratified analyses, significance was spotted in populations of Chinese descent, in retrospective studies, in hospital-based studies, in age-matched case-control studies, in studies enrolling patients with mean body mass index < 25 kg/m2 and in studies with total sample size ≥ 240. Heterogeneity was improved for most stratified comparisons. Further in hypertensive patients, the 64Trp/64Arg heterozygote carriers had significantly higher systolic (WMD = 0.87 mmHg, 95% CI: 0.391.35, P < 0.001) and diastolic (WMD = 0.88 mmHg, 95% CI: 0.59~1.17, P < 0.001) BP than 64Trp/64Trp homozygote carriers. Altogether, ADRB3 gene Trp64Arg mutation was significantly associated with an increased predisposition toward hypertension and elevated systolic/diastolic BP in hypertensive patients, suggesting that Trp64Arg is an important hypertension-susceptibility marker.
本荟萃分析旨在检验β3 -肾上腺素能受体编码基因（ADRB3）中的错义突变Trp64Arg与高血压风险及血压（BP）变化之间的关联。对三个公开数据库进行了系统检索，以查找截至2016年12月发表的文章。由两名研究人员独立进行资格评估和数据提取。汇总估计值以比值比（OR）或加权平均差（WMD）及其95%置信区间（95%CI）表示。分别有21项（3750/4225例患者/对照）和17项（6100名受试者）关于高血压风险和BP变化的个体研究。综合分析显示，Trp64Arg突变与高血压风险显著增加相关，特别是，与64Trp/64Trp纯合子携带者相比，64Trp/64Arg杂合子携带者患高血压的可能性高1.23倍（OR = 1.23，95%CI：1.021.46，P = 0.021）。所有综合比较的发表偏倚极低。在分层分析中，在中国血统人群、回顾性研究、基于医院的研究、年龄匹配的病例对照研究、纳入平均体重指数<25 kg/m2患者的研究以及总样本量≥240的研究中发现了显著性。大多数分层比较的异质性得到改善。进一步在高血压患者中，64Trp/64Arg杂合子携带者的收缩压（WMD = 0.87 mmHg，95%CI：0.391.35，P < 0.001）和舒张压（WMD = 0.88 mmHg，95%CI：0.59~1.17，P < 0.001）显著高于64Trp/64Trp纯合子携带者。总之，ADRB3基因Trp64Arg突变与高血压易感性增加以及高血压患者收缩压/舒张压升高显著相关，表明Trp64Arg是一个重要的高血压易感性标志物。
