The effect of polymorphisms of the β2-adrenergic receptor on the response to regular use of albuterol in asthma

Elliot Israel, Jeffrey M. Drazen, Stephen B. Liggett, Homer A. Boushey, Reuben M. Cherniack, Vernon M. Chinchilli, David M. Cooper, John V. Fahy, James E. Fish, Jean G. Ford, Monica Kraft, Susan Kunselman, Stephen C. Lazarus, Robert F. Lemanske, Richard J. Martin, Diane E. Mclean, Stephen P. Peters, Edwin K. Silverman, Christine A. Sorkness, Stanley J. SzeflerScott T. Weiss, Chandri N. Yandava

Research output: Contribution to journalArticle

474 Citations (Scopus)

Abstract

Inhaled β-adrenergic agonists are the most commonly used medications for the treatment of asthma although there is evidence that regular use may produce adverse effects in some patients. Polymorphisms of the β2- adrenergic receptor (β2-AR) can affect regulation of the receptor. Smaller studies examining the effects of such polymorphisms on the response to β- agonist therapy have produced inconsistent results. We examined whether polymorphisms at codon 16 (β2-AR-16) and codon 27 (β2-AR-27) of the β2- AR might affect the response to regular versus as-needed use of albuterol by genotyping the 190 asthmatics who had participated in a trial examining the effects of regular versus as needed albuterol use. During the 16-wk treatment period there was a small decline in morning peak expiratory flow in patients homozygous for arginine at B2-AR-16 (Arg/Arg) who used albuterol regularly. This effect was magnified during a 4-wk run out period, during which all patients returned to using as-needed albuterol, so that by the end of the study Arg Arg patients who had regularly used albuterol had a morning peak expiratory flow 30.5 ± 12.1 L/min lower (p = 0.012) than Arg/Arg patients who had used albuterol on an as needed basis. There was no decline in peak flow with regular use of albuterol in patients who were homozygous for glycine at β2-AR-16. Evening peak expiratory flow also declined in the Arg/Arg patients who used albuterol regularly but not in those who used albuterol on an as-needed basis. No significant differences in outcomes between regular and as-needed treatment were associated with polymorphisms at position 27 of the β2-AR. No other differences in asthma outcomes that we investigated occurred in relation to these β2-AR polymorphisms. Polymorphisms of the β2-AR may influence airway responses to regular inhaled β-agonist treatment.

Original languageEnglish (US)
Pages (from-to)75-80
Number of pages6
JournalAmerican journal of respiratory and critical care medicine
Volume162
Issue number1
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

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Albuterol
Adrenergic Receptors
Asthma
Codon
Therapeutics
Adrenergic Agonists
Glycine
Arginine

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

The effect of polymorphisms of the β2-adrenergic receptor on the response to regular use of albuterol in asthma. / Israel, Elliot; Drazen, Jeffrey M.; Liggett, Stephen B.; Boushey, Homer A.; Cherniack, Reuben M.; Chinchilli, Vernon M.; Cooper, David M.; Fahy, John V.; Fish, James E.; Ford, Jean G.; Kraft, Monica; Kunselman, Susan; Lazarus, Stephen C.; Lemanske, Robert F.; Martin, Richard J.; Mclean, Diane E.; Peters, Stephen P.; Silverman, Edwin K.; Sorkness, Christine A.; Szefler, Stanley J.; Weiss, Scott T.; Yandava, Chandri N.

In: American journal of respiratory and critical care medicine, Vol. 162, No. 1, 01.01.2000, p. 75-80.

Research output: Contribution to journalArticle

Israel, E, Drazen, JM, Liggett, SB, Boushey, HA, Cherniack, RM, Chinchilli, VM, Cooper, DM, Fahy, JV, Fish, JE, Ford, JG, Kraft, M, Kunselman, S, Lazarus, SC, Lemanske, RF, Martin, RJ, Mclean, DE, Peters, SP, Silverman, EK, Sorkness, CA, Szefler, SJ, Weiss, ST & Yandava, CN 2000, 'The effect of polymorphisms of the β2-adrenergic receptor on the response to regular use of albuterol in asthma', American journal of respiratory and critical care medicine, vol. 162, no. 1, pp. 75-80. https://doi.org/10.1164/ajrccm.162.1.9907092
Israel, Elliot ; Drazen, Jeffrey M. ; Liggett, Stephen B. ; Boushey, Homer A. ; Cherniack, Reuben M. ; Chinchilli, Vernon M. ; Cooper, David M. ; Fahy, John V. ; Fish, James E. ; Ford, Jean G. ; Kraft, Monica ; Kunselman, Susan ; Lazarus, Stephen C. ; Lemanske, Robert F. ; Martin, Richard J. ; Mclean, Diane E. ; Peters, Stephen P. ; Silverman, Edwin K. ; Sorkness, Christine A. ; Szefler, Stanley J. ; Weiss, Scott T. ; Yandava, Chandri N. / The effect of polymorphisms of the β2-adrenergic receptor on the response to regular use of albuterol in asthma. In: American journal of respiratory and critical care medicine. 2000 ; Vol. 162, No. 1. pp. 75-80.
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AU - Israel, Elliot

AU - Drazen, Jeffrey M.

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AU - Boushey, Homer A.

AU - Cherniack, Reuben M.

AU - Chinchilli, Vernon M.

AU - Cooper, David M.

AU - Fahy, John V.

AU - Fish, James E.

AU - Ford, Jean G.

AU - Kraft, Monica

AU - Kunselman, Susan

AU - Lazarus, Stephen C.

AU - Lemanske, Robert F.

AU - Martin, Richard J.

AU - Mclean, Diane E.

AU - Peters, Stephen P.

AU - Silverman, Edwin K.

AU - Sorkness, Christine A.

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AU - Weiss, Scott T.

AU - Yandava, Chandri N.

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N2 - Inhaled β-adrenergic agonists are the most commonly used medications for the treatment of asthma although there is evidence that regular use may produce adverse effects in some patients. Polymorphisms of the β2- adrenergic receptor (β2-AR) can affect regulation of the receptor. Smaller studies examining the effects of such polymorphisms on the response to β- agonist therapy have produced inconsistent results. We examined whether polymorphisms at codon 16 (β2-AR-16) and codon 27 (β2-AR-27) of the β2- AR might affect the response to regular versus as-needed use of albuterol by genotyping the 190 asthmatics who had participated in a trial examining the effects of regular versus as needed albuterol use. During the 16-wk treatment period there was a small decline in morning peak expiratory flow in patients homozygous for arginine at B2-AR-16 (Arg/Arg) who used albuterol regularly. This effect was magnified during a 4-wk run out period, during which all patients returned to using as-needed albuterol, so that by the end of the study Arg Arg patients who had regularly used albuterol had a morning peak expiratory flow 30.5 ± 12.1 L/min lower (p = 0.012) than Arg/Arg patients who had used albuterol on an as needed basis. There was no decline in peak flow with regular use of albuterol in patients who were homozygous for glycine at β2-AR-16. Evening peak expiratory flow also declined in the Arg/Arg patients who used albuterol regularly but not in those who used albuterol on an as-needed basis. No significant differences in outcomes between regular and as-needed treatment were associated with polymorphisms at position 27 of the β2-AR. No other differences in asthma outcomes that we investigated occurred in relation to these β2-AR polymorphisms. Polymorphisms of the β2-AR may influence airway responses to regular inhaled β-agonist treatment.

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