The mutation of Trp64Arg in β3-adrenoreceptor-encoding gene is significantly associated with increased hypertension risk and elevated blood pressure: a meta-analysis

Hualing Yang, Dongmiao Cai, Qingping Zhu, Dongjin Wu, Qingxiang Wang and Zhanxiang Wang _

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Oncotarget. 2017; 8:46480-46490. https://doi.org/10.18632/oncotarget.16666

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Hualing Yang1,2,*, Dongmiao Cai1,2,*, Qingping Zhu2,3,*, Dongjin Wu1,2, Qingxiang Wang1,2 and Zhanxiang Wang2,4

1Department of Anesthesiology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China

2The First Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China

3Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China

4Department of Neurosurgery, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China

*These authors contributed equally to this work

Correspondence to:

Hualing Yang, email: [email protected]

Zhanxiang Wang, email: [email protected]

Keywords: hypertension, β3-adrenoreceptor, polymorphism, blood pressure, meta-analysis

Received: February 03, 2017     Accepted: March 16, 2017     Published: March 29, 2017


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: 1.02~1.46, 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: 0.39~1.35, 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.

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