S-Space College of Medicine/School of Medicine (의과대학/대학원) Immunology (면역학전공) Journal Papers (저널논문_면역학전공)
Association and functional relevance of E237G, a polymorphism of the high-affinity immunoglobulin E-receptor beta chain gene, to airway hyper-responsiveness
- Kim, Y. K.; Park, H. W.; Yang, J. S.; Oh, S. Y.; Chang, Y. S.; Shin, E. S.; Lee, J. E.; Kim, S.; Gho, Y. S.; Cho, S. H.; Min, K. U.; Kim, Y. Y.
- Issue Date
- Clin Exp Allergy. 2007 Apr;37(4):592-8.
- Adolescent; Amino Acid Sequence; Asthma/*genetics/immunology/physiopathology; Bronchial Provocation Tests; Child; Cohort Studies; Genetic Predisposition to Disease; Genotype; Humans; Immunoglobulin E/blood; Molecular Sequence Data; Phenotype; *Polymorphism, Single Nucleotide; Receptors, IgE/*genetics
- BACKGROUND: The hyper-sensitivity reaction of IgE, with its high-affinity receptors (FcepsilonRI), is central to the phenomenon of atopic diseases. OBJECTIVE: To evaluate the genetic effects of non-synonymous single-nucleotide polymorphisms (SNPs) of FcepsilonRI 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 FcepsilonRI-alpha, FcepsilonRI-beta, and FcepsilonRI-gamma 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 FcepsilonRI-beta: 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 FcepsilonRI-beta, which results in an intolerant amino acid substitution.
- 0954-7894 (Print)
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