Premium
Gene–gene interaction between interleukin‐4 and interleukin‐4 receptor α in Korean children with asthma
Author(s) -
Lee S.G.,
Kim B.S.,
Kim J.H.,
Lee S.Y.,
Choi S.O.,
Shim J.Y.,
Hong T.J.,
Hong S.J.
Publication year - 2004
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2004.02015.x
Subject(s) - genotype , asthma , immunology , odds ratio , interleukin 13 , eosinophil , allele , restriction fragment length polymorphism , heterozygote advantage , interleukin 4 receptor , interleukin 4 , interleukin , polymorphism (computer science) , allergy , immunoglobulin e , allele frequency , biology , medicine , gene , genetics , cytokine , antibody
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.