Meta-analysis of the association of β2-adrenergic receptor polymorphisms with asthma phenotypes

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.