Gene–gene interaction between interleukin-4 and interleukin-4 receptor 
in Korean children with asthma
Authors: S.-G. Lee1; B.-S. Kim2; J.-H. Kim2; S.-Y. Lee2; S.-O. Choi1; J.-Y. Shim3; T.-J. Hong4; S.-J. Hong2
Source: Clinical & Experimental Allergy, Volume 34, Number 8, August 2004 , pp. 1202-1208(7)
Publisher: Blackwell Publishing
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Abstract:
Background Interleukin-4 receptor (IL-4R), 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-4R polymorphisms are associated with susceptibility to asthma and whether there are gene–gene interactions between IL-4 and IL-4R 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-4R 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-4R 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-4R 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-4R 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-4R Arg551 allele significantly increases an individual's susceptibility to asthma.
Keywords:
asthma;
atopy;
bronchial hyper-responsiveness;
eosinophil;
gene–gene interaction;
IL-4;
IL-4R;
polymorphism
Document Type: Research article
DOI: 10.1111/j.1365-2222.2004.02015.x
Affiliations: 1: Asan Institute for Life Sciences, University of Ulsan, Seoul, Korea 2: Department of Pediatrics, University of Ulsan College of Medicine, Seoul, Korea 3: Department of Pediatrics, Sungkyunkwan University College of Medicine, Poongnap-Dong, Songpa-Gu, Seoul, Korea and 4: Department of Internal Medicine, Pusan National University, Ami-Dong Seo-Gu, Pusan, Korea
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