Analysis of the association between bronchial hyperresponsiveness and genetic polymorphism of beta2-adrenoceptor in adolescents with long-term asthma remission

Kang, Hee; Koh, Young Yull

Abstract

PURPOSE: We hypothesized that the persisting bronchial hyperresponsiveness (BHR) of adolescents with asthma remission may be controlled mainly by genetic factors, and the BHR of symptomatic asthma by airway inflammation. beta2-adrenoceptor gene is considered to be a candidate gene in the development of BHR. Thus, beta2-adrenoceptor gene polymorphism may be associated with the BHR of adolescents with asthma remission, but not with the BHR of symptomatic asthma. To evaluate this hypothesis, beta2-adrenoceptor gene polymorphism at 2 sites (Arg16-Gly, Gln27-Glu) were examined.
METHODS
Two hundred two adolescents with BHR (PC20<18 mg/mL) and long term remission (neither asthma-related symptoms nor medication during the previous 2 years) of their asthma (remission group), 182 adolescents with symptomatic asthma (symptomatic group), and 200 healthy adolescents (control group) were studied. Asthma phenotypes were determined using methacholine bronchial provocation test and skin prick test. Genotypes of beta2-adrenoceptor polymorphism were evaluated by PCR-based methods.
RESULTS
Gly/Gly allele and Gly16-Gln27 haplotype were more prevalent in the remission group than in the control group (P=0.01, P=0.02), although there was no difference between the symptomatic group and the control group. In the remission group, there was significant difference in geometric mean of PC20 among the 3 groups subdivided by the number of Gly16-Gln27 haplotype, showing that the Gly16-Gln27 haplotype was positively associated with BHR. However, no association was found between Gly16-Gln27 haplotype and BHR in the symptomatic group.
CONCLUSION
This study demonstrates that beta2-adrenoceptor polymorphism at amino acid 16 and 27 was associated with BHR persisting in adolescents with asthma remission.