Gene-gene interactions for asthma and plasma total IgE concentration in Chinese children.
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.
Chan
Iris H S
IH
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
Leung
Ting F
TF
Tang
Nelson L S
NL
Li
Chung Y
CY
Sung
Ying M
YM
Wong
Gary W K
GW
Wong
Chun K
CK
Lam
Christopher W K
CW
D000293:Adolescent; D001249:Asthma / Q000235:genetics* / Q000276:immunology*; D054414:Chemokine CCL17; D019742:Chemokines, CC / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D007231:Infant, Newborn; D018793:Interleukin-13 / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D011110:Polymorphism, Genetic; D019948:Receptors, Interleukin-4 / Q000235:genetics*
C106230:CCL17 protein, human; D054414:Chemokine CCL17; D019742:Chemokines, CC; D018793:Interleukin-13; D019948:Receptors, Interleukin-4; D007073:Immunoglobulin E