Variants of the ADRB2 Gene in COPD: Systematic Review and Meta-Analyses of Disease Risk and Treatment Response.

The β-adrenergic receptor (ADRB) is an important regulator of airway smooth muscle tone in chronic obstructive pulmonary disease (COPD). Variants that impair ADRB function could increase disease risk or reduce the response to endogenous and inhaled adrenergic agonists in COPD. We performed a systematic review and three meta-analyses to assess whether three functional variants (Thr164Ile, Arg16Gly, and Gln27Glu) in the ADRB gene are associated with elevated risk of disease or reduced therapeutic response to inhaled β-agonists in COPD. We searched the medical literature from 1966 to 2017 and found 16 relevant studies comprising 85381 study subjects. The meta-analyses found no significant association between ADRB genotype and COPD risk. The summary odds ratios (ORs) for COPD in Thr164Ile homozygotes and heterozygotes were 2.57 (95% confidence interval (CI): 0.54-12.4) and 1.17 (95% CI: 0.96-1.44), respectively. Corresponding summary ORs for COPD in Arg16Gly homozygotes and heterozygotes were 0.97 (95% CI: 0.76-1.22) and 1.01 (95% CI: 0.81-1.26), while summary ORs for COPD in Gln27Glu homozygotes and heterozygotes were 1.00 (95% CI: 0.80-1.25) and 0.94 (95% CI: 0.69-1.24), respectively. When stratified by ethnicity, the summary ORs for COPD did not differ from 1.0 for any of the ADRB variants among Asian, Caucasian, or African populations. We found no consistent associations between ADRB genotype and treatment response to inhaled β-agonists in COPD. This systematic review and meta-analyses found that COPD risk and response to inhaled β-agonists were not associated with Thr164Ile, Arg16Gly, and Gln27Glu genotypes. However, identified cases of Thr164Ile were few, and additional studies of rare ADRB genotypes are required.