PMID- 22376040 OWN - NLM STAT- MEDLINE DCOM- 20120504 LR - 20221207 IS - 1532-4303 (Electronic) IS - 0277-0903 (Linking) VI - 49 IP - 3 DP - 2012 Apr TI - Gene-gene interactions between candidate gene polymorphisms are associated with total IgE levels in Korean children with asthma. PG - 243-52 LID - 10.3109/02770903.2012.660294 [doi] AB - OBJECTIVE: To investigate associations between total serum immunoglobulin E (IgE) levels and single nucleotide polymorphisms (SNPs) from eight candidate genes (IL-4 rs2243250, IL-4Ralpha rs1805010, IL-13 rs20541, IL-13Ralpha1 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-13Ralpha1, 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-4Ralpha, IL-13, IL-13Ralpha1, 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-4Ralpha 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-13Ralpha1, IL-4Ralpha 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-4Ralpha, IL-13, IL-13Ralpha1, 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-13Ralpha1 polymorphisms showed synergistic effects in terms of increased total serum IgE levels in the present cohort. FAU - Choi, Won-Ah AU - Choi WA AD - Asan Institute for Life Sciences, Seoul, Korea. FAU - Kang, Mi-Jin AU - Kang MJ FAU - Kim, Young-Joon AU - Kim YJ FAU - Seo, Ju-Hee AU - Seo JH FAU - Kim, Hyung-Young AU - Kim HY FAU - Kwon, Ji-Won AU - Kwon JW FAU - Yu, Jinho AU - Yu J FAU - Park, Seoung-Ju AU - Park SJ FAU - Lee, Yong-Chul AU - Lee YC FAU - Hong, Soo-Jong AU - Hong SJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120229 PL - England TA - J Asthma JT - The Journal of asthma : official journal of the Association for the Care of Asthma JID - 8106454 RN - 0 (CTLA-4 Antigen) RN - 0 (CTLA4 protein, human) RN - 0 (IL13RA1 protein, human) RN - 0 (IL4R protein, human) RN - 0 (Interleukin-13) RN - 0 (Interleukin-13 Receptor alpha1 Subunit) RN - 0 (Interleukin-4 Receptor alpha Subunit) RN - 0 (Lipopolysaccharide Receptors) RN - 37341-29-0 (Immunoglobulin E) SB - IM MH - Asian People MH - Asthma/*blood/diagnosis/*genetics/immunology MH - CTLA-4 Antigen/genetics MH - Child MH - Child, Preschool MH - Female MH - Gene Frequency/genetics MH - Humans MH - Immunoglobulin E/*blood MH - Interleukin-13/genetics MH - Interleukin-13 Receptor alpha1 Subunit/genetics MH - Interleukin-4 Receptor alpha Subunit/genetics MH - Lipopolysaccharide Receptors/genetics MH - Male MH - Polymorphism, Single Nucleotide/*genetics MH - Skin Tests EDAT- 2012/03/02 06:00 MHDA- 2012/05/05 06:00 CRDT- 2012/03/02 06:00 PHST- 2012/03/02 06:00 [entrez] PHST- 2012/03/02 06:00 [pubmed] PHST- 2012/05/05 06:00 [medline] AID - 10.3109/02770903.2012.660294 [doi] PST - ppublish SO - J Asthma. 2012 Apr;49(3):243-52. doi: 10.3109/02770903.2012.660294. Epub 2012 Feb 29.