BACKGROUND: Atopy is a major risk factor in the development of asthma. Interleukin (IL)-4 and the IL-4 receptor alpha (IL-4R alpha ) play crucial roles for the binding and signal transduction of the IL-4 and IL-13 that participate in IgE production. OBJECTIVE: This study was performed to determine whether IL-4 and IL-4R alpha polymorphisms contribute to the susceptibility to atopic asthma, or non-atopic asthma, and to see if those polymorphisms are associated with the clinical parameters of asthma. Also, the genetic interactions between IL-4 and IL-4R alpha polymorphisms were investigated to see if they were associated with the clinical parameters of asthma. METHOD: An association study was conducted of the known polymorphisms of the IL-4 promoter ( 590C/T) and IL-4R alpha (Ile50Val, Arg551Gln), with atopic asthma or non- atopic asthma, in Korean children. One hundred and twenty- eight atopic asthmatic children, 21 non-atopic asthma, and 108 non-atopic healthy children were enrolled. The asthma phenotypes were determined by a physician, and the bronchial responsiveness to methacholine, and the genotypes of the IL-4 and IL-4R alpha polymorphisms identified using a PCR-RFLP method and DNA sequencing. RESULT: The allele frequencies of the IL-4 promoter (-590C/T) and Ile50Val of the IL-4R alpha gene polymorphism showed no statistical difference between the atopic asthma, non-atopic asthma, and non-atopic healthy children, and was not associated with the clinical parameters of asthma. In the polymorphisms of the Arg551Gln of the IL-4R alpha gene, the frequency of the Arg/Gln heterozygote and Arg/Arg homozygote in atopic asthma (25.7%, OR=2.08, 95% CI 1.07~4.02) was significantly increased compared to that in the non-atopic healthy children (14.8%). A meaningful gene-gene interaction between the IL-4 promoter ( 590) and IL-4Ralpha Arg551Gln, which was shown to be associated with PC20 (mg/ml) (P=0.040), was detected in the atopic asthmatics. And this study showed the trend that IgE (IU/ml) was higher if subjects had two risk alleles (P=0.074). CONCLUSION: These data suggest that the arginine 551 allele of the IL-4R alpha gene is the atopic asthma susceptibility gene in Korean children. In addition, a potential gene-gene interaction, between the IL-4 promoter ( 590) and IL-4R alpha Arg551Gln, may contribute to the clinical phenotype of asthma.