Effect of Polymorphism of the β2-Adrenergic Receptor on Response to Regular Use of Albuterol in AsthmaIsrael E.a · Drazen J.M.a · Liggett S.B.h · Boushey H.A.b · Cherniack R.M.i · Chinchilli V.M.f · Cooper D.M.c · Fahy J.V.b · Fish J.E.j · Ford J.G.d · Kraft M.i · Kunselman S.f · Lazarus S.C.b · Lemanske, Jr. R.F.g · Martin R.J.i · McLean D.E.e · Peters S.P.j · Silverman E.K.k · Sorkness C.A.g · Szefler S.J.i · Weiss S.T.k · Yandava C.N.k · for the National Heart, Lung, and Blood Institute’s Asthma Clinical Research Network
aBrigham and Women’s Hospital and Harvard Medical School, Boston, Mass., bUniversity of California at San Francisco, Calif., cThe Children’s Hospital and Harvard Medical School, Boston, Mass., dHarlem Hospital Center, New York, N.Y., eMontefiore Medical Center, New York, N.Y., fPennsylvania State University, Hershey, Pa., gUniversity of Wisconsin, Madison, Wisc., hUniversity of Cincinnati Medical Center, Cincinnati, Ohio, iNational Jewish Medical and Research Center, Denver, Colo., jThomas Jefferson University, Philadelphia, Pa., and kHarvard Medical School, Boston, Mass., USA
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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