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Published on: April 13, 2010
Bronchodilator response in relation to beta2-adrenoceptor haplotype in patients with asthma
D Robin Taylor1, Michael J Epton, Martin A Kennedy
1Otago Respiratory Research Unit and Department of Preventive and Social Medicine, Dunedin School of Medicine, New Zealand. robin.taylor@stonebow.otago.ac.nz
Rationale:
Genetic variation of the beta2-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 beta2-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 beta2-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 beta2-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 FEV(1)) 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 beta2-agonist. The confounding effect of tolerance resulting from regular beta2-agonist use must be controlled when assessing the pharmacogenetic influences on clinical outcomes with beta2-agonists.
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