This Article Full Text Full Text (PDF) All Versions of this Article: 200501-092OCv1 172/6/700    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Taylor, D. R. Articles by Herbison, G. P. Search for Related Content PubMed PubMed Citation Articles by Taylor, D. R. Articles by Herbison, G. P.

Bronchodilator Response in Relation to 2-Adrenoceptor Haplotype in Patients with Asthma

Otago Respiratory Research Unit and Department of Preventive and Social Medicine, Dunedin School of Medicine; and Canterbury Respiratory Research Unit and Department of Pathology, Gene Structure and Function Laboratory, Christchurch School of Medicine, University of Otago, Dunedin, New Zealand

Correspondence and requests for reprints should be addressed to Professor D. Robin Taylor, M.D., F.R.C.P.(C)., Dunedin School of Medicine, P.O. Box 913, Dunedin, New Zealand. E-mail: robin.taylor{at}stonebow.otago.ac.nz

Rationale: Genetic variation of the 2-adrenoceptor (ADRB2) influences receptor function in vitro. There are reports that, in vivo, bronchodilator response is related to ADRB2 genotype, and that clinical outcomes during chronic therapy with 2-agonist drugs are also influenced by genotype. Whether these features are related to single nucleotide polymorphisms or to combinations (haplotypes) is unclear. Objectives: Our aim was to measure bronchodilator response in patients with asthma stratified by ADRB2 haplotype. This was done after eliminating the confounding effect of prior drug treatment with inhaled 2-agonists and corticosteroids. Methods: ADRB2 haplotype was determined in 176 patients with asthma, of whom 161 harbored the six most common combinations. Treatment with inhaled 2-agonists and inhaled corticosteroids was withheld for appropriate intervals. Spirometric changes 20 minutes after a single dose of albuterol (2.5 mg by nebulizer) were then recorded. Results: There were no significant differences in bronchodilator response (% improvement in FEV₁) with respect to any of the major ADRB2 haplotypes or genotypes. Conclusions: Genetic variation of the ADRB2 does not influence the immediate response to inhaled 2-agonist. The confounding effect of tolerance resulting from regular 2-agonist use must be controlled when assessing the pharmacogenetic influences on clinical outcomes with 2-agonists.

Key Words: asthma therapy • 2-adrenoceptor • 2-agonist • haplotype

This article has been cited by other articles:

				U. Frey Asthma as a nonlinear complex dynamic system: a novel approach to understand the temporal behaviour of chronic asthma and its response to {beta}-agonists Eur. Respir. Rev., June 1, 2008; 17(108): 67 - 69. [Full Text] [PDF]

				G. A. Hawkins, K. Tantisira, D. A. Meyers, E. J. Ampleford, W. C. Moore, B. Klanderman, S. B. Liggett, S. P. Peters, S. T. Weiss, and E. R. Bleecker Sequence, Haplotype, and Association Analysis of ADRbeta2 in a Multiethnic Asthma Case-Control Study Am. J. Respir. Crit. Care Med., November 15, 2006; 174(10): 1101 - 1109. [Abstract] [Full Text] [PDF]

				S. E. Wenzel and R. Covar Update in asthma 2005. Am. J. Respir. Crit. Care Med., April 1, 2006; 173(7): 698 - 706. [Full Text] [PDF]

				M. E. Wechsler, E. Lehman, S. C. Lazarus, R. F. Lemanske Jr., H. A. Boushey, A. Deykin, J. V. Fahy, C. A. Sorkness, V. M. Chinchilli, T. J. Craig, et al. beta-Adrenergic Receptor Polymorphisms and Response to Salmeterol Am. J. Respir. Crit. Care Med., March 1, 2006; 173(5): 519 - 526. [Abstract] [Full Text] [PDF]

				P. W. Ind Bigger May Be Better: Targeted {beta}2-Agonist Therapy Am. J. Respir. Crit. Care Med., September 15, 2005; 172(6): 656 - 657. [Full Text] [PDF]