ADRB2 polymorphisms and risk of COPD exacerbations: the Rotterdam Study

Background: The role of the β2-adrenergic receptor (ADRB2) gene in patients with chronic obstructive pulmonary disease (COPD) is unclear. Aim: We investigated the association of ADRB2 polymorphisms and the risk of COPD exacerbations in patients treated with inhaled β2-agonists. Methods: Within the Rotterdam Study, we followed 1,147 COPD patients until the first COPD exacerbation or end of follow-up and extracted rs1042713 (16Arg>Gly) and rs1042714 (27Gln>Glu) in ADRB2. Exposure to inhaled β2-agonists was assessed based on dispensing data and categorised into current, past or no use on the index date (date of COPD exacerbation for cases and on the same day of follow-up for the controls). The associations of the SNPs with COPD exacerbations were assessed using Cox proportional hazards regression analysis, adjusting for age, sex, use of inhaled corticosteroids, daily dosage of β2-agonists and smoking. Results: In current users of inhaled β2-agonists, the risk of COPD exacerbations decreased by 21% (HR:0.79, 95%CI: 0.67-0.94) for each copy of the A allele (Arg) of rs1042713 and by 19% (HR:0.81, 95%CI: 0.70-0.95) for each copy of the C allele (Gln) of rs1042714. Current users of β2-agonists carrying the haplotype Arg16Gln27 had a significantly lower risk (HR:0.76, 95%CI: 0.63-0.90) of COPD exacerbations compared to the haplotype Gly16Glu27. Conclusion: The haplotype Arg16Gln27 in the ADRB2 gene was associated with a decreased risk of COPD exacerbation in current users of inhaled β2-agonists.