Effect of Polymorphism of the β2-Adrenergic Receptor on Response to Regular Use of Albuterol in AsthmaIsrael E. · Drazen J.M. · Liggett S.B. · Boushey H.A. · Cherniack R.M. · Chinchilli V.M. · Cooper D.M. · Fahy J.V. · Fish J.E. · Ford J.G. · Kraft M. · Kunselman S. · Lazarus S.C. · Lemanske, Jr. R.F. · Martin R.J. · McLean D.E. · Peters S.P. · Silverman E.K. · Sorkness C.A. · Szefler S.J. · Weiss S.T. · Yandava C.N. · for the National Heart, Lung, and Blood Institute’s Asthma Clinical Research Network
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.
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