Chest
Clinical InvestigationsASTHMAEffects of Genetic Polymorphism on Ex Vivo and In Vivo Function of β2-Adrenoceptors in Asthmatic Patients
Section snippets
Patients
Sixty patients with stable mild-to-moderate asthma were enrolled in the study; we had no prior knowledge of theirβ 2-adrenoceptor genotype. Analysis ofβ 2-adrenoceptor polymorphism was subsequently performed on a post hoc basis in all patients at the end of the study. All patients were required to have a diagnosis of stable asthma of mild-to-moderate severity, according to American Thoracic Society criteria.14 All patients were nonsmokers and were required to have an FEV1 of at least 60% of
Results
The demographic data are summarized in Table 1 for homozygous and heterozygous (Het) polymorphisms at codon 16 and 27. There were no significant differences between the polymorphisms for age, FEV1, or inhaled corticosteroid dose. Moreover, there were no differences between the groups in terms of prior use of long- or short-acting β2-agonists.
The results for lymphocyte β2-adrenoceptor parameters are summarized in Table 2. Receptor binding parameters (Bmax and Kd) showed no differences between
Discussion
Our results show that genetic polymorphism at codon 16 or 27 does not influence lymphocyte β2-adrenoceptor binding density or affinity. There was also no impairment of functional coupling to the G-protein as evidenced by maximal isoproterenol-stimulated adenylyl cyclase activity, which was similar for each of the polymorphisms. Although basal cAMP activity was significantly different between Glu-27 and Het-27, there was no difference when comparing the two homozygous polymorphisms at either
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This study was supported by a joint grant from the Universities of Dundee and Nottingham. Dr. Hall is a National Asthma Campaign supportedsenior research fellow. Dr. Tan was also supported by the National Asthma Campaign.