Bronchodilator Response in Relation to β2-Adrenoceptor Haplotype in Patients with Asthma

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Abstract
Rationale: Genetic variation of the 2-adrenoceptor (ADRB2) influ- ences 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 re- sponse 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. Treat- ment 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 broncho- dilator response (% improvement in FEV1) with respect to any of the majorADRB2haplotypesor genotypes.Conclusions:Geneticvariation of the ADRB2 does not influence the immediate response to inhaled 2-agonist. The confounding effect of tolerance resulting from reg- ular 2-agonist use must be controlled when assessing the pharma- cogenetic influences on clinical outcomes with 2-agonists.