Polymorphism of the beta2-adrenoceptor and the response to long-term beta2-agonist therapy in asthma.
Polymorphisms affecting amino acids 16 and 27 of the beta2-adrenoceptor alter receptor regulation in vitro. Whether these polymorphisms alter the response to beta2-agonist therapy in asthma is unknown. In a previous study of 64 asthmatics, most experienced a deterioration in asthma control during regular inhaled beta2-agonist (fenoterol) treatment, while a minority improved. We have determined the beta2-adrenoceptor genotypes in these subjects, to establish whether changes in asthma control during the earlier study were influenced by beta2-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 beta2-agonist treatment on asthma control were compared between genotypes. There was no association between genotype and change in overall asthma control during regular beta2-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 beta2-agonist treatment was not related to beta2-receptor polymorphism.
Hancox
R J
RJ
Dept of Medicine, University of Otago, Dunedin, New Zealand.
Sears
M R
MR
Taylor
D R
DR
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics; D004311:Double-Blind Method; D015536:Down-Regulation; D005280:Fenoterol / Q000008:administration & dosage / Q000627:therapeutic use*; D005838:Genotype; D018698:Glutamic Acid / Q000235:genetics; D005998:Glycine / Q000235:genetics; D006801:Humans; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D018343:Receptors, Adrenergic, beta-2; D005280:Fenoterol; D018698:Glutamic Acid; D005998:Glycine