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Gene-gene interactions for asthma and plasma total IgE concentration in Chinese children
Iris H S Chan1, Ting F Leung, Nelson L S Tang
1Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
Background:
Asthma is a complex disease resulting from interactions between multiple genes and environmental factors. Study of gene-gene interactions could provide insight into asthma pathophysiology.
Objective:
We investigated the interaction among 12 different loci in 8 candidate genes and asthma and increased plasma total IgE concentrations in 240 Chinese asthmatic subjects and 140 control subjects.
Methods:
Genotyping was performed by means of RFLP analysis. Multifactor dimensionality reduction and logistic regression were used to analyze gene-gene interactions.
Results:
A significant interaction was found between R130Q in the IL-13 gene (IL13) and I50V in the IL-4 receptor alpha gene (IL4RA) on the risk of asthma, with a cross-validation consistency of 10 of 10 and a prediction error of 33.7% (P = .014). The odds ratio of the high-risk to low-risk group was 2.6 (95% CI, 1.4-5.0; P = .004). For increased plasma total IgE concentration, the best 2-locus model consisted of R130Q in IL13 and C-431T in the thymus and activation-regulated chemokine gene (TARC). This model showed a maximum cross-validation consistency of 10 and a minimum prediction error of 36.1% (P = .022). The odds ratio of the high-risk to low-risk group was 3.9 (95% CI, 2.0-7.7; P = .0001). Logistic regression revealed significant interactions between IL13 and IL4RA for asthma (P = .042) and IL13 and TARC for increased total IgE concentration (P = .012).
Conclusions:
Our data suggest significant interactions between IL13 and IL4RA for asthma and IL13 and TARC for increased plasma total IgE concentrations in Chinese children.
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