Gene-Gene Interaction Between CCR3 and Eotaxin Genes: The Relationship With Blood Eosinophilia in Asthma

PURPOSE: Eosinophils function as an effector cell in the development of asthma and allergic disease. Eotaxins are cytokines that promote pulmonary eosinophilia via the receptor CCR3. Single-nucleotide polymorphisms (SNPs) in CCR3 and eotaxin genes are associated with asthma. In this study, genetic interactions among SNPs of several eotaxin genes and CCR3 were assessed and their relationship with blood eosinophilia in asthma was examined. METHODS: A total of 533 asthmatics were enrolled in this study. Asthmatics with eosinophilia (>0.5×10(9)/L) were compared with those without eosinophilia (≤0.5×10(9)/L). Chi-square tests were used to compare SNP frequencies. Two different models were used to evaluate gene-gene interactions: logistic regression and generalized multifactor dimensionality reduction (GMDR). RESULTS: EOT2+304C>A (29L>I) was significantly associated with 3 of the 4 CCR3 SNPs among asthmatics with eosinophilia (P=0.037-0.009). EOT2+304C>A (29L>I) and the CCR3 SNPs were also significantly associated with blood eosinophilia in an interaction model constructed by logistic regression (P=0.0087). GMDR analysis showed that the combination of EOT2+304C>A (29L>I) and CCR3-174C>T was the best model (accuracy=0.536, P=0.005, CVC 9/10). CONCLUSIONS: The epistatic influence of CCR3 on eotaxin gene variants indicates that these variants may be candidate markers for eosinophilia in asthma.