Meta-analysis of the association of β2-adrenergic receptor polymorphisms with asthma phenotypes
Meta-analysis of the association of β2-adrenergic receptor polymorphisms with asthma phenotypes
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DOI：
10.1016/j.jaci.2004.12.1119
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发表时间：
2005-05-01
影响因子：
14.2
通讯作者：
Ioannidis, JPA
中科院分区：
文献类型：
--
作者：
Contopoulos-Ioannidis, DG;Manoli, EN;Ioannidis, JPA
背景：β2-肾上腺素能受体基因的两种常见多态性（Arg16Gly 和 Gln27Glu）已被广泛研究其与哮喘相关表型的可能关联，但个别研究的结果尚无定论。 目的：我们旨在定量整合关于 Arg16Gly 和 Gln27Gu 多态性与哮喘、夜间哮喘、哮喘严重程度和支气管哮喘之间关系的现有证据。方法：使用随机效应模型对病例对照和队列研究进行荟萃分析。结果：荟萃分析共纳入 28 项研究。总结估计表明，Gly16 和 Glu27 等位基因均不会导致总体哮喘易感性（比值比 [OR]，1.01；95% CI，0.90-1.13；OR，0.95；95% CI，0.83-1.09）或支气管高反应性（OR，0.90；95% CI，分别为 0.77-1.05；OR，1.07；95% CI，0.94-1.22。 Glyl 6 与夜间哮喘有很强的相关性（OR，2.20；95% CI，1.56-3.11），与重度或中度而非轻度哮喘的相关性较弱（OR，1.42；95% CI，1.04-1.94）。 Glu27 等位基因没有观察到这种效应（OR，1.02；95% CI，0.74-1.40；OR，0.82；95% CI，0.59-1.14）。此外，有证据表明，Gly16 纯合子比 Arg16 纯合子具有更高的夜间哮喘风险（OR，5.15；95% CI，2.44-10.84）和哮喘严重程度（OR，2.84；95% CI，1.62-4.96）。结论：β 2-肾上腺素能受体基因的 Gly16 等位基因容易患夜间哮喘，这也可以解释与哮喘严重程度的关系。这两种多态性都不会调节支气管高反应性或轻度哮喘的风险。
Background: Two common polymorphisms of the beta 2-adrenergic receptor gene (Arg16Gly and Gln27Glu) have been extensively studied for their possible association with asthma-related phenotypes, but the results of individual studies have been inconclusive.Objective: We aimed to integrate quantitatively the available evidence on the association of the Arg16Gly and the Gln27Gu polymorphisms with asthma, nocturnal asthma, asthma severity, and bronchial hyperresponsiveness.Methods: Meta-analysis of case-control and cohort studies using random effects models.Results: A total of 28 studies were included in the meta-analysis. The summary estimates suggested that neither the Gly16 nor the Glu27 allele contributes to asthma susceptibility overall (odds ratio [OR], 1.01; 95% CI, 0.90-1.13; and OR, 0.95; 95% CI, 0.83-1.09, respectively) or to bronchial hyperresponsiveness (OR, 0.90; 95% CI, 0.77-1.05; and OR, 1.07; 95% CI, 0.94-1.22, respectively). There was a strong association of Glyl 6 with nocturnal asthma (OR, 2.20; 95% CI, 1.56-3.11) and a less strong association with severe or moderate rather than milder asthma (OR, 1.42; 95% CI, 1.04-1.94). No such effects were seen for the Glu27 allele (OR, 1.02; 95% CI, 0.74-1.40; and OR, 0.82; 95% CI, 0.59-1.14, respectively). Moreover, there was evidence that Gly16 homozygotes had a much higher risk for nocturnal asthma (OR, 5.15; 95% CI, 2.44-10.84) and asthma severity (OR, 2.84; 95% CI, 1.62-4.96) than the Arg16 homozygotes.Conclusion: The Gly16 allele of the beta 2-adrenergic receptor gene predisposes to nocturnal asthma, and this may also explain the association with asthma severity. Neither polymorphism modulates the risk for bronchial hyperresponsiveness or mild asthma.