The effect of beta2-adrenoceptor haplotypes on bronchial hyper-responsiveness in patients with asthma.
The beta2-adrenoceptor exhibits genetic polymorphism which may be clinically relevant in terms of treatment response or bronchial hyper-responsiveness (BHR). The combined effect of these genotypes, or the haplotype, has not been fully characterized in terms of BHR. We performed a retrospective analysis of the effects of haplotypes of amino acid substitution at position 16 (Gly/Arg) and position 27 (Gln/Glu) on spirometry and BHR to methacholine and adenosine monophosphate (AMP) in 594 asthmatic patients. There was a significant (P < 0.05) overall effect for forced expiratory volume (FEV(1)) but not after correction for steroid dose and atopic status. There were no significant differences for BHR to methacholine or AMP between the different haplotypes and no difference between the numbers of patients with or without clinically relevant BHR. Methacholine PD20 geometric mean-fold difference was 1.63 (95% CI: 0.95-2.80) between Arg-Arg/Gln-Gln and Gly-Gly/Gln-Gln and 1.26 (95% CI: 0.75-2.11) between Gly-Gly/Gln-Gln and Gly-Gly/Glu-Glu. The degree of BHR to indirect and direct stimuli does not differ between beta2-adrenoceptor haplotypes, and haplotypes cannot be used to predict BHR in patients presenting with asthma. Although beta2-adrenoceptor haplotypes do not predict BHR they may be important in predicting response to bronchodilator therapy.