Polymorphism of the β2-adrenoceptor and the response to long-term β2-agonist therapy in asthma

Abstract

Polymorphisms affecting amino acids 16 and 27 of the β2-adrenoceptor alter receptor regulation in vitro. Whether these polymorphisms alter the response to β2-agonist therapy in asthma is unknown. In a previous study of 64 asthmatics, most experienced a deterioration in asthma control during regular inhaled β2-agonist (fenoterol) treatment, while a minority improved. We have determined the β2-adrenoceptor genotypes in these subjects, to establish whether changes in asthma control during the earlier study were influenced by β2-adrenoceptor polymorphism. The genotypes coding for amino acids 16 and 27 were identified in 60 subjects using allele- specific polymerase chain reaction. The effects of regular β2-agonist treatment on asthma control were compared between genotypes. There was no association between genotype and change in overall asthma control during regular β2-agonist treatment. Only two of 10 markers of asthma control showed changes that were significantly associated with genotype: subjects homozygous for glycine at position 16 had no increase in bronchial responsiveness to methacholine during regular treatment; subjects homozygous for glutamic acid at position 27 had no increase in evening peak expiratory flow rates during regular treatment. These differences are the opposite of those that would have been predicted by the results of in vitro studies. In these subjects, the deleterious response to regular inhaled β2-agonist treatment was not related to β2-receptor polymorphism.