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Vol. 124, No. 1-3, 2001
Issue release date: January–March 2001

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

Israel 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
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Abstract

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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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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References

  1. Drazen JM, Israel E, Boushey HA, Chinchilli VM, Fahy JV, Fish JE, Lazarus SC, Lemanske RF, Martin RJ, Peters SP, Sorkness C, Szefler SJ: Comparison of regularly scheduled with as-needed use of albuterol in mild asthma. Asthma Clinical Research Network. N Engl J Med 1996;335:841–847.
  2. Reihsaus E, Innis M, MacIntyre N, Liggett SB: Mutations in the gene encoding for the beta2-adrenergic receptor in normal and asthmatic subjects. Am J Respir Cell Mol Biol 1993;8:334–339.
  3. Green SA, Cole G, Jacinto M, Innis M, Liggett SB: A polymorphism of the human beta 2-adrenergic receptor within the fourth transmembrane domain alters ligand binding and functional properties of the receptor. J Biol Chem 1993;268:23116–23121.
  4. Green SA, Turki J, Innis M, Liggett SB: Amino-terminal polymorphisms of the human beta 2-adrenergic receptor impact distinct agonist-promoted regulatory properties. Biochemistry 1994;33:9414–9419.
  5. Turki J, Lorenz JN, Green SA, Donnelly ET, Jacinto M, Liggett SB: Myocardial signaling defects and impaired cardiac function of a human beta 2-adrenergic receptor polymorphism expressed in transgenic mice. Proc Natl Acad Sci USA 1996;93:10483–10488.
  6. Green SA, Turki J, Bejarano P, Hall IP, Liggett SB: Influence of beta(2)-adrenergic receptor genotypes on signal transduction in human airway smooth muscle cells. Am J Respir Cell Mol Biol 1995;13:25–33.
  7. Liggett SB: Polymorphisms of the beta-2-adrenergic receptor and asthma. Am J Respir Crit Care Med 1997;156:S156–S162.


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