Effect of Polymorphism of the β₂-Adrenergic Receptor on Response to Regular Use of Albuterol in Asthma

Background: Regular use of inhaled β-adrenergic agonists may have adverse effects in some asthma patients. Polymorphisms of the β₂-adrenergic receptor (β₂-AR) can affect its regulation; however, results of smaller studies of the effects of such polymorphisms on response to β-agonist therapy have been inconsistent. Methods: We examined the possible effects of polymorphisms at codons 16 (β₂-AR-16) and 27 (β₂-AR-27) on response to albuterol by genotyping 190 asthmatics who had participated in a trial of regular versus as-needed albuterol use. Results: During the 16-week treatment period, patients homozygous for arginine (Arg/Arg) at β₂-AR-16 who used albuterol regularly had a small decline in morning peak expiratory flow (AM PEF). This effect was magnified during a 4-week run-out period, when all patients returned to as-needed albuterol only. By the end of the study, Arg/Arg subjects who had used albuterol regularly had an AM PEF 30.5 ± 12.1 liters/min lower (p = 0.012) than Arg/Arg patients who had used albuterol as needed only. Subjects homozygous for glycine at β₂-AR-16 showed no such decline. Evening PEF also declined in the Arg/Arg regular but not in as-need albuterol users. No significant differences between regular and as-needed treatment were associated with polymorphisms at β₂-AR-27. Conclusions: Polymorphisms of the β₂-AR may influence airway responses to regular inhaled β-agonist treatment.