The glutamine 27 beta(2)-adrenoceptor polymorphism is associated with elevated IgE levels in asthmatic families

[摘要] 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 allergic disease remains to be established. Objective: This large family study examines the contributions of these polymorphisms in determining the heritable component of markers for allergic disease in asthmatic families. Methods: Three hundred twenty-four individuals from 60 families multiplex for asthma selected by means of an asthmatic proband were characterized for the following markers of allergic disease: asthma, atopy, and serum IgE. The polymerase chain reaction was used to generate 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 performed. 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 and beta(2)-adrenoceptor polymorphisms at locus 27 (p = 0.037), However, there was no association between either the arginine-glycine 16 or the glutamine-glutamate 27 beta(2)-adrenoceptor polymorphism and an increased risk of asthma or atopy per se. Conclusion: The glutamine 27 beta(2)-adrenoceptor polymorphism appears to contribute to IgE variability in families with asthma. However, it seems that although both amino acid 16 and 27 beta(2)-adrenoceptor polymorphisms are disease-modifying in subjects with asthma, they do not contribute markedly to the development of the asthmatic phenotype.

[发布日期] 1997-08-01

[关键词] beta(2)-adrenoceptor polymorphism;IgE;asthma;atopy;chromosome 5q;genetics of asthma