Gene-Gene Interactions between Candidate Gene Polymorphisms Are Associated with Total IgE Levels in Korean Children with Asthma

Objective. To investigate associations between total serum immunoglobulin E (IgE) levels and single nucleotide polymorphisms (SNPs) from eight candidate genes (IL-4 rs2243250, IL-4R alpha rs1805010, IL-13 rs20541, IL-13R alpha 1 rs2495636, CD14 rs2569190, tumor necrosis factor-alpha (TNF-alpha) rs1800629, cytotoxic T lymphocyte-associated antigen (CTLA4) rs231775, FCER1B rs1441585) in children with asthma and to evaluate gene-gene interactions. Methods. A total of 669 Korean children with asthma (n = 544 atopic n = 125 non-atopic) were included. Asthma phenotypes, total serum IgE levels, and methacholine challenge test results were evaluated. SNPs were genotyped using the polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method. Multi-factor dimensionality reduction (MDR) was used to analyze gene-gene interactions. Results. The combination of the IL-13, IL-13R alpha 1, and CTLA4 polymorphisms was selected through MDR analysis of the data pertaining to children with atopic and non-atopic asthma (accuracy = 0.5459, cross validation consistency (CVC) = 10/10). The IL-4R alpha, IL-13, IL-13R alpha 1, CD14, and CTLA4 polymorphisms were selected as the best model of increased total serum IgE levels in non-atopic and atopic asthma (asthma: accuracy = 0.4726, CVC = 10/10; atopic asthma: accuracy = 0.4573, CVC = 10/10). Both the IL-4R alpha and the IL-13 polymorphisms were correlated with the IgE level. ANOVA analysis revealed that the combinations of the CTLA4 and IL-13, IL-13 and IL-13R alpha 1, IL-4R alpha and IL-13, and CD14 and IL-13 polymorphisms were all significantly associated with increased total serum IgE levels. Conclusions. The best model of increased IgE level included the IL-4R alpha, IL-13, IL-13R alpha 1, CD14, and CTLA4 polymorphisms. Of the various interactions between these polymorphisms, the combinations of the CTLA4 and IL-13 polymorphisms and the IL-13 and IL-13R alpha 1 polymorphisms showed synergistic effects in terms of increased total serum IgE levels in the present cohort.