Polymorphisms in the β₂ adrenergic receptor and bronchodilator response, bronchial hyperresponsiveness, and rate of decline in lung function in smokers

Background: Non-specific bronchial hyperresponsiveness (NSBH) is a known predictor of accelerated rate of decline in lung function in smokers. Polymorphisms of the β₂ adrenergic receptor (ADRB2) have previously been associated with NSBH and bronchodilator response (BDR) in asthmatics. Based on these associations, we hypothesised that ADRB2 polymorphisms would be associated with NSBH and BDR as well as an accelerated rate of decline in lung function among smokers. Methods: The prevalence of two ADRB2 polymorphisms, Arg16→Gly and GIn27→Glu, was examined in 587 smokers chosen from the NHLBI Lung Health Study for having the fastest (n=282) and slowest (n=305) 5 year rate of decline in forced expiratory volume in 1 second (FEV₁; mean ΔFEV₁ -4.14 and + 1.08% predicted/year, respectively). Results: Contrary to our hypothesis, no ADRB2 allele or haplotype was associated with NSBH, BDR, or rate of decline in lung function. However, there was a significant negative association between heterozygosity at position 27 and a fast decline in lung function (adjusted odds ratio 0.56, 95% CI 0.40 to 0.78, p=0.0007). Conclusions: Heterozygosity at position 27 may be protective against an accelerated rate of decline in lung function. The polymorphism at position 16 does not contribute to the rate of decline in lung function, measures of NSBH, or BDR in smokers.