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Published ahead of print on June 23, 2005, doi:10.1164/rccm.200501-092OC
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American Journal of Respiratory and Critical Care Medicine Vol 172. pp. 700-703, (2005)
© 2005 American Thoracic Society
doi: 10.1164/rccm.200501-092OC

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

D. Robin Taylor, Michael J. Epton, Martin A. Kennedy, Andrew D. Smith, Steven Iles, Allison L. Miller, Matthew D. Littlejohn, Jan O. Cowan, Tracey Hewitt, Maureen P. Swanney, Karen P. Brassett and G. Peter Herbison

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 {beta}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 {beta}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 {beta}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 {beta}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 {beta}2-agonist. The confounding effect of tolerance resulting from regular {beta}2-agonist use must be controlled when assessing the pharmacogenetic influences on clinical outcomes with {beta}2-agonists.

Key Words: asthma therapy • {beta}2-adrenoceptor • {beta}2-agonist • haplotype




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