Gene-gene interactions between candidate gene polymorphisms are associated with total IgE levels in Korean children with asthma
Autor: | Ji Won Kwon, Soo-Jong Hong, Young Joon Kim, Yong Chul Lee, Ju Hee Seo, Won Ah Choi, Seoung Ju Park, Mi Jin Kang, Hyung Young Kim, Jinho Yu |
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Rok vydání: | 2012 |
Předmět: |
Pulmonary and Respiratory Medicine
Male Candidate gene CD14 Lipopolysaccharide Receptors Single-nucleotide polymorphism Immunoglobulin E Polymorphism Single Nucleotide Antigen Asian People Gene Frequency Polymorphism (computer science) medicine Immunology and Allergy Humans CTLA-4 Antigen Child Gene Asthma Skin Tests Genetics Interleukin-13 biology business.industry Interleukin-4 Receptor alpha Subunit medicine.disease Interleukin-13 Receptor alpha1 Subunit Child Preschool Pediatrics Perinatology and Child Health Immunology biology.protein Female business |
Zdroj: | The Journal of asthma : official journal of the Association for the Care of Asthma. 49(3) |
ISSN: | 1532-4303 |
Popis: | 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.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.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.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. |
Databáze: | OpenAIRE |
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