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.
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