Back to Search Start Over

Gene-gene and gene-environmental interactions of childhood asthma: a multifactor dimension reduction approach.

Authors :
Su MW
Tung KY
Liang PH
Tsai CH
Kuo NW
Lee YL
Source :
PloS one [PLoS One] 2012; Vol. 7 (2), pp. e30694. Date of Electronic Publication: 2012 Feb 15.
Publication Year :
2012

Abstract

Background: 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.<br />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.<br />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.

Details

Language :
English
ISSN :
1932-6203
Volume :
7
Issue :
2
Database :
MEDLINE
Journal :
PloS one
Publication Type :
Academic Journal
Accession number :
22355322
Full Text :
https://doi.org/10.1371/journal.pone.0030694