Association of β2-adrenergic receptor gene polymorphisms (rs1042713, rs1042714, rs1042711) with asthma risk: a systematic review and updated meta-analysis

BACKGROUND: The published data on the association between β2-adrenergic receptor gene polymorphisms and asthma susceptibility are inconclusive. To derive a more precise estimation of this association, a meta-analysis was performed. METHODS: A literature search was conducted in PubMed, Web of Science, EMBASE, Wanfang, and the China National Knowledge Infrastructure (CNKI) databases to identify eligible studies. The pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to calculate the strength of the association. A sensitivity analysis was performed to evaluate the influence of individual studies on the overall effect estimates, and funnel plots and Egger’s tests were used for indications of publication bias. RESULTS: Seventy three studies with three single nucleotide polymorphisms (SNP) (rs1042713, c.G46A, p.Gly16Arg; rs1042714, c.G79C, p.Gln27Glu; rs1042711, c.T-47C, p.Cys19Arg) were finally identified. For the rs1042713 polymorphism, no significant association with asthma risk was found in the overall population. However, a significant protective association was found in the Indian population in the dominant model comparison (OR = 0.72, 95% CI = 0.59–0.87, I(2) = 25%, studies = 5, cases = 1190, controls = 1241). A significant risk association was found in the Arab population in the dominant model comparison (OR = 1.75, 95% CI = 1.14–2.70, I(2) = 0%, studies = 2, cases = 307, controls = 361) and the homozygote model comparison (OR = 1.88, 95% CI = 1.17–3.02, I(2) = 0%, studies = 2, cases = 307, controls = 361), and in the Hispanic-Latino population in the dominant model comparison (OR = 1.68, 95% CI = 1.10–2.55, I(2) = 77%, studies = 5, cases = 1026, controls = 1412). For the rs1042714 polymorphism, we found a significant association in the recessive model comparison (OR = 0.83, 95% CI = 0.70–0.98, I(2) = 44%, studies = 52, cases = 8242, controls = 16,832), the homozygote genotype comparison (OR = 0.84, 95% CI = 0.72–0.98, I(2) = 25%, studies = 52, cases = 8242, controls = 16,832) and the allelic genetic model (OR = 0.91, 95% CI = 0.83–0.99, I(2) = 59%, studies = 52, cases = 8242, controls = 16,832) in the overall population. When stratified by age, a significant association was also found in children in the recessive model comparison (OR = 0.59, 95% CI = 0.39–0.88, I(2) = 58%, studies = 18, cases = 2498, controls = 2510) and the homozygote genotype comparison (OR = 0.63, 95% CI = 0.43–0.92, I(2) = 46%, studies = 18, cases = 2498, controls = 2510), but not in adult. For the rs1042711 polymorphism, no significant associations were found in the any genetic model. CONCLUSION: The meta-analysis suggests that the ADRB2 rs1042714 polymorphism has a protective association with asthma in the overall population and the pediatric subgroup.