Association between bronchodilating response to short-acting β-agonist and non-synonymous single-nucleotide polymorphisms of β2-adrenoceptor gene

Background With beta-agonists being the most widely used agents in the treatment of asthma, in vitro studies reported that beta(2)-adrenergic receptor (ADRB2) polymorphisms are associated with agonist-promoted down-regulation. Objective The present population-based study aimed to evaluate the association between bronchodilating response to inhaled short-acting beta-agonist and two non-synonymous single-nucleotide polymorphisms (SNPs) of ADRB2 (ADRB2-16 and ADRB2-27). Methods Two hundred and nine children with reduction in forced expiratory volume in 1s of more than 20% on methacholine bronchial challenge underwent bronchodilating response testing 5min after the inhalation of 200 mu g of albuterol. Of these 209, 195 gave peripheral blood for genotyping of ADRB2 polymorphisms. Results The bronchodilating response was significantly higher in subjects with the homozygous Arg16 than in those with the homozygous Gly16. It was further demonstrated that haplotype pairs of the homozygous Arg16Gln27 and of the heterozygous Arg16Gln27/Gly16Glu27 showed the highest bronchodilating responses, and the haplotype pairs of the homozygous Gly16Gln27 the lowest response. As a whole, the bronchodilating response was more positively associated with the combined quantity of Arg16 and Glu27 polymorphisms than with that of Arg16 alone. Conclusion Non-synonymous SNPs of ADRB2 at codons 16 and 27 is significantly associated with bronchodilating response to inhaled short acting beta-agonists.