Eotaxin family (Eotaxin 1,2 and 3) recruits and activates CCR3-bearing cells such as eosinophil, mast cells, and Th2 lymphocytes that play a major role in allergic disorders. We examined the polygenetic effects of the Eotaxin gene family in a Korean population. Gene-gene interactions were tested using a multistep approach with multifactor dimensionality reduction (MDR) method between asthmatics and normal controls. The overall best MDR model of the main effect single nucleotide polymorphisms (SNPs) included EOT2 + 1272A > G and EOT3 + 77C > T (model 1) [testing accuracy 0.597, cross-validation consistency (CVC) 10/10, P < 0.001]. The overall best MDR model of the SNPs with no main effects included EOT2 + 304C > A, EOT3 + 716A > G, and EOT3 + 1579G > A (model 2) (testing accuracy 0.616, CVC 10/10, P < 0.001). Model 3 was obtained by including the MDR variables for models 1 and 2. This new composite model predicted asthma with better accuracy than either model 1 or model 2 (testing accuracy 0.643, CVC 10/10, P < 0.001). The detection of statistical interaction models is one evidence of gene-gene interactions among Eotaxin genes, and this interaction is thought to influence the development of asthma. Although the models are limited to determining statistical interactions within a population, they may be useful for identifying groups at high risk of developing asthma.