TY - JOUR
T1 - Gene-gene interaction between interleukin-4 and interleukin-4 receptor α in Korean children with asthma
AU - Lee, S. G.
AU - Kim, B. S.
AU - Kim, J. H.
AU - Lee, S. Y.
AU - Choi, S. O.
AU - Shim, J. Y.
AU - Hong, T. J.
AU - Hong, S. J.
PY - 2004/8
Y1 - 2004/8
N2 - 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 Gin/Gin 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.
AB - 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 Gin/Gin 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.
KW - Asthma
KW - Atopy
KW - Bronchial hyper-responsiveness
KW - Eosinophil
KW - Gene-gene interaction
KW - IL-4
KW - IL-4Rα
KW - Polymorphism
UR - https://www.scopus.com/pages/publications/4143122127
U2 - 10.1111/j.1365-2222.2004.02015.x
DO - 10.1111/j.1365-2222.2004.02015.x
M3 - Article
C2 - 15298559
AN - SCOPUS:4143122127
SN - 0954-7894
VL - 34
SP - 1202
EP - 1208
JO - Clinical and Experimental Allergy
JF - Clinical and Experimental Allergy
IS - 8
ER -
