Background The hyper-sensitivity reaction of IgE, with its high-affinity receptors (FcɛRI), is central to the phenomenon of atopic diseases.
Objective To evaluate the genetic effects of non-synonymous single-nucleotide polymorphisms (SNPs) of FcɛRI on intermediate phenotypes of asthma, i.e. atopy and airway hyper-responsiveness (AHR), in the Korean general population.
Subjects and methods Atopy and AHR were evaluated in a cohort of 2055 subjects, aged 10–18 years, using skin prick tests (SPTs) for common aeroallergens and total serum IgE and methacholine bronchial provocation tests. All FcɛRI-α, FcɛRI-β, and FcɛRI-γ gene exons of 24 healthy subjects were sequenced to locate informative non-synonymous SNPs (minor allele frequency >2%). Informative SNPs were then scored, using the high-throughput single base extension method. Relative risk (RR) was determined by multiple logistic regression analysis, after adjusting for confounding factors. The functional relevance of non-synonymous SNPs was analysed using the sorting intolerant from tolerant (SIFT) program.
Results The SNP search found only one informative non-synonymous SNP in FcɛRI-β: E237G (minor allele frequency=0.21). The positive rate of AHR was lower among subjects with the 237*E allele than among those with 237*G [RR (95% confidence interval)=0.41 (0.19–0.89); P=0.01]. However, the E237G substitution was not associated with either a positive SPT response or total serum IgE levels. Sequence evolution analysis predicted that the E237G variation is an intolerant amino acid substitution, with functional importance.
Conclusion In the Korean general population, AHR is significantly associated with the E237G polymorphism of FcɛRI-β, which results in an intolerant amino acid substitution.