POLYMORPHISM OF THE BETA(2)-ADRENOCEPTOR AND THE RESPONSE TO LONG-TERM BETA(2)-AGONIST THERAPY IN ASTHMA

Polymorphisms affecting amino acids 16 and 27 of the beta(2)-adrenocep tor alter receptor regulation in vitro, Whether these polymorphisms al ter the response to beta(2)-agonist therapy in asthma is unknown. In a previous study of 64 asthmatics, most experienced a deterioration in asthma control during regular inhaled beta 2-agonist (fenoterol) treat ment, while a minority improved. We have determined the beta(2)-adreno ceptor genotypes in these subjects, to establish whether changes in as thma control during the earlier study were influenced by beta(2)-adren oceptor polymorphism. The genotypes coding for amino acids 16 and 27 w ere identified in 60 subjects using allele-specific polymerase chain r eaction, The effects of regular beta(2)-agonist treatment on asthma co ntrol were compared between genotypes. There was no association betwee n genotype and change in overall asthma control during regular beta(2) -agonist treatment. Only two of 10 markers of asthma control showed ch anges that were significantly associated with genotype: subjects homoz ygous for glycine at position 16 had no increase in bronchial responsi veness to methacholine during regular treatment; subjects homozygous f or glutamic acid at position 27 had no increase in evening peak expira tory how rates during regular treatment. These differences are the opp osite of those that would have been predicted by the results of in vit ro studies. In these subjects, the deleterious response to regular inh aled beta(2)-agonist treatment was not related to beta(2)-receptor pol ymorphism.