title: Gene-gene interactions between candidate gene polymorphisms are associated with total IgE levels in Korean children with asthma.
abstract: OBJECTIVE
  To investigate associations between total serum immunoglobulin E (IgE) levels and single nucleotide polymorphisms (SNPs) from eight candidate genes (IL-4 rs2243250, IL-4Rα rs1805010, IL-13 rs20541, IL-13Rα1 rs2495636, CD14 rs2569190, tumor necrosis factor-alpha (TNF-α) 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-13Rα1, 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-4Rα, IL-13, IL-13Rα1, 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-4Rα 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-13Rα1, IL-4Rα 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-4Rα, IL-13, IL-13Rα1, 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-13Rα1 polymorphisms showed synergistic effects in terms of increased total serum IgE levels in the present cohort.
authors.affiliation: Asan Institute for Life Sciences, Seoul, Korea.
authors.forename: Won-Ah
authors.initials: WA
authors.lastname: Choi
authors.forename: Mi-Jin
authors.initials: MJ
authors.lastname: Kang
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Kim
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Seo
authors.forename: Hyung-Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Kwon
authors.forename: Jinho
authors.initials: J
authors.lastname: Yu
authors.forename: Seoung-Ju
authors.initials: SJ
authors.lastname: Park
authors.forename: Yong-Chul
authors.initials: YC
authors.lastname: Lee
authors.forename: Soo-Jong
authors.initials: SJ
authors.lastname: Hong
mesh_terms: D044466:Asian People; D001249:Asthma / Q000097:blood* / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D060908:CTLA-4 Antigen / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D018793:Interleukin-13 / Q000235:genetics; D053661:Interleukin-13 Receptor alpha1 Subunit / Q000235:genetics; D053662:Interleukin-4 Receptor alpha Subunit / Q000235:genetics; D018950:Lipopolysaccharide Receptors / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012882:Skin Tests
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C508181:IL13RA1 protein, human; C504000:IL4R protein, human; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D053662:Interleukin-4 Receptor alpha Subunit; D018950:Lipopolysaccharide Receptors; D007073:Immunoglobulin E