Blackwell Publishing Journal Backfiles 1879-2005
Background Interleukin-4 receptor α (IL-4Rα), which binds IL-4 and IL-13, is involved in signal transduction of those cytokines that lead to IgE production, and is also a key functional component of the Th2 lymphocyte phenotype.Objective To determine whether IL-4 and IL-4Rα polymorphisms are associated with susceptibility to asthma and whether there are gene–gene interactions between IL-4 and IL-4Rα polymorphisms.Methods We genotyped three groups of Korean children, consisting of 196 atopic asthmatics, 60 non-atopic asthmatics, and 100 healthy children, for an IL-4 promoter polymorphism (C-590T) and three IL-4Rα polymorphisms (Ile50Val, Pro478Ser, and Arg551Gln) using PCR-RFLP (restriction fragment length polymorphism) assays.Results The allele frequencies of the IL-4 (C/T) polymorphism and the Ile50Val and Pro478Ser polymorphisms of IL-4Rα did not differ statistically among the three groups of children. For the Arg551Gln polymorphism, the combined genotype frequency of the Arg/Gln heterozygote and the Arg/Arg homozygote was significantly higher in atopic asthmatics (27.6%) than in healthy children (16.0%) (odds ratio (OR)=1.97, 95% CI (confidence interval)=1.07–3.71). The eosinophil fraction (%) and bronchial responsiveness were higher in children with the Arg/Gln and Arg/Arg genotype than in those with the Gln/Gln genotype (P=0.036 and 0.024, respectively). In asthmatic children, combinations of the IL-4 CT/TT genotype and the IL-4Rα Arg/Gln and Arg/Arg genotypes were associated with significantly increased risk for development of asthma (OR=3.70, 95% CI=1.07–12.78, P=0.038).Conclusions In Korean children, the IL-4Rα Arg551 allele may play a role in susceptibility to atopic asthma and correlate with markers of asthma pathogenesis, including increased eosinophil fraction and enhanced bronchial hyper-responsiveness. In addition, a significant gene–gene interaction between the IL-4-590C and the IL-4Rα Arg551 allele significantly increases an individual's susceptibility to asthma.
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