臺大公衛學院-流行病學與預防醫學研究所;臺大公衛學院-基因、環境與健康研究中心;臺大醫學院-藥學系暨研究所;YUNG-LING LEESu, Ming-WeiMing-WeiSuTung, Kuan-YenKuan-YenTungPI-HUI LIANGLiang, Pi-HuiPi-HuiLiangTsai, Ching-HuiChing-HuiTsaiKuo, Nai-WeiNai-WeiKuoLee, Yungling LeoYungling LeoLeeChristensen, Brock C.Brock C.Christensen2018-09-102018-09-102012http://www.scopus.com/inward/record.url?eid=2-s2.0-84857097161&partnerID=MN8TOARShttp://scholars.lib.ntu.edu.tw/handle/123456789/374853Background: The importance of gene-gene and gene-environment interactions on asthma is well documented in literature, but a systematic analysis on the interaction between various genetic and environmental factors is still lacking. Methodology/Principal Findings: We conducted a population-based, case-control study comprised of seventh-grade children from 14 Taiwanese communities. A total of 235 asthmatic cases and 1,310 non-asthmatic controls were selected for DNA collection and genotyping. We examined the gene-gene and gene-environment interactions between 17 single-nucleotide polymorphisms in antioxidative, inflammatory and obesity-related genes, and childhood asthma. Environmental exposures and disease status were obtained from parental questionnaires. The model-free and non-parametrical multifactor dimensionality reduction (MDR) method was used for the analysis. A three-way gene-gene interaction was elucidated between the gene coding glutathione S-transferase P (GSTP1), the gene coding interleukin-4 receptor alpha chain (IL4Ra) and the gene coding insulin induced gene 2 (INSIG2) on the risk of lifetime asthma. The testing-balanced accuracy on asthma was 57.83% with a cross-validation consistency of 10 out of 10. The interaction of preterm birth and indoor dampness had the highest training-balanced accuracy at 59.09%. Indoor dampness also interacted with many genes, including IL13, beta-2 adrenergic receptor (ADRB2), signal transducer and activator of transcription 6 (STAT6). We also used likelihood ratio tests for interaction and chi-square tests to validate our results and all tests showed statistical significance. Conclusions/Significance: The results of this study suggest that GSTP1, INSIG2 and IL4Ra may influence the lifetime asthma susceptibility through gene-gene interactions in schoolchildren. Home dampness combined with each one of the genes STAT6, IL13 and ADRB2 could raise the asthma risk. ? 2012 Su et al.110 bytestext/html[SDGs]SDG3DNA; DNA; glutathione transferase P1; GSTP1 protein, human; IL4R protein, human; INSIG2 protein, human; interleukin 4 receptor alpha; membrane protein; signal peptide; accuracy; ADRB2 gene; article; asthma; case control study; child; childhood asthma; controlled study; female; gene; gene interaction; genotype; genotype environment interaction; GSTP1 gene; health status; human; IL13 gene; INSIG2 gene; interleukin 4 receptor alpha gene; major clinical study; male; population research; prematurity; questionnaire; school child; single nucleotide polymorphism; STAT6 gene; Taiwan; validation process; adolescent; asthma; comparative study; genetic predisposition; genetics; multifactor dimensionality reduction; newborn; polymerase chain reaction; single nucleotide polymorphism; Taiwan; Adolescent; Asthma; Case-Control Studies; Child; DNA; Female; Gene-Environment Interaction; Genetic Predisposition to Disease; Genotype; Glutathione S-Transferase pi; Humans; Infant, Newborn; Interleukin-4 Receptor alpha Subunit; Intracellular Signaling Peptides and Proteins; Male; Membrane Proteins; Multifactor Dimensionality Reduction; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Taiwanjournal article10.1371/journal.pone.0030694