Association of Fc epsilon R1-beta polymorphisms with asthma and associatedtraits in Australian asthmatic families

Background Asthma is a genetically complex disease, and is characterized by elevated serum immunoglobulin E (IgE) levels, elevated blood eosinophil co unts and increased airway responsiveness. Polymorphisms in the beta subunit of the high affinity receptor for IgE (Fc epsilon R1-beta) have been previ ously associated with these phenotypes and with an increased risk of asthma . Objective To investigate the association of all known bi-allelic polymorphi sms in Fc epsilon R1-beta to asthma and quantitative traits associated with asthma in a selected sample of Australian asthmatic children and their nuc lear families. Methods Australian Caucasian nuclear families (n = 134 subjects) were recru ited on the basis of a child proband with current, severe, symptomatic asth ma. The quantitative traits assessed included serum levels of total IgE and specific IgE to house dust mite and mixed grass, blood eosinophil counts a nd the dose-response slope of the forced expiratory volume in is to histami ne provocation. Results Neither the Leu181 nor the E237G mutations were detected in this po pulation. Allele B of RsaI intron 2 (RsaI-in2*B) was significantly associat ed with physician-diagnosed asthma lever) (P = 0.002). Alleles of both the RsaI-in2 and RsaI exon 7 (RsaI-ex7) polymorphisms were significantly associ ated with log, total serum IgE levels and the combined RAST index. RsaI-ex7 was also associated with log, blood eosinophil counts. These associations were independent of age, sex and familial correlations. Conclusion This study supports a role for the Fc epsilon R1-beta gene or a nearby gene in the pathogenesis of asthma.