THE GLUTAMINE-27 BETA(2)-ADRENOCEPTOR POLYMORPHISM IS ASSOCIATED WITHELEVATED IGE LEVELS IN ASTHMATIC FAMILIES

Background: The beta(2)-adrenoceptor polymorphisms occurring at amino acid positions 16 (arginine to glycine) and 27 (glutamine to glutamate ) are known to be functionally relevant and also disease-modifying in subjects with asthma. However, the contribution of these polymorphisms to the development of the asthmatic phenotype or other markers for al lergic disease remains to be established. Objective: This large family study examines the contributions of these polymorphisms in determinin g the heritable component of markers for allergic disease in asthmatic families. Methods: Three hundred twenty-four individuals from 60 fami lies multiplex for asthma selected by means of an asthmatic proband we re characterized for the following markers of allergic disease: asthma , atopy, and serum IgE. The polymerase chain reaction was used to gene rate a 234 base pair fragment spanning the region of interest, and the beta(2)-adrenoceptor polymorphism was then defined by allele-specific oligonucleotide hybridization. Segregation analysis was then performe d. Results: We found a significant association (p = 0.009) between the glutamine 27 beta(2)-adrenoceptor polymorphism and elevated levels of IgE, which was supported by the observation of linkage between IgE an d beta(2)-adrenoceptor polymorphisms at locus 27 (p = 0.037), However, there was no association between either the arginine-glycine 16 or th e glutamine-glutamate 27 beta(2)-adrenoceptor polymorphism and an incr eased risk of asthma or atopy per se. Conclusion: The glutamine 27 bet a(2)-adrenoceptor polymorphism appears to contribute to IgE variabilit y in families with asthma. However, it seems that although both amino acid 16 and 27 beta(2)-adrenoceptor polymorphisms are disease-modifyin g in subjects with asthma, they do not contribute markedly to the deve lopment of the asthmatic phenotype.