Multilocus analysis of atopy in Korean children using multifactor-dimensionality reduction.
BACKGROUND
Atopy is considered to be a complex genetic trait and does not follow a simple mendelian pattern of inheritance. It is now well recognised that gene-gene interactions are important in complex genetic disease.


OBJECTIVE
To analyse the influence of gene-gene interactions in the development of atopy.


METHODS
A total of 2055 ethnically identical participants aged 10-18 years living in rural areas on Jeju Island, Korea, were randomly recruited. Atopy was defined as a positive skin prick test response to one or more common inhalant allergens. Gene-gene interactions among 12 polymorphic loci were analysed in the seven candidate genes of atopy using the multidimensionality-reduction method.


RESULTS
A significant interaction was found between V297I in the gene coding vascular endothelial growth factor receptor 2 (KDR) and -308G-->A in the gene coding tumour necrosis factor (TNF)alpha on the risk of atopy, with a cross-validation consistency of 10 out of 10 and a prediction error of 35.9% (p = 0.001). Conventional logistic regression also revealed significant interactions between KDR and TNF for atopy. Individuals with the variant allele of -308G-->A in TNF (GA or AA) and V297I in KDR (VI or II) had a significantly higher risk of atopy (OR 2.23; 95% CI 1.48 to 3.57).


CONCLUSIONS
KDR and TNF may synergistically influence the development of atopy through gene-gene interaction in Korean children and adolescents.
Park
Heung-Woo
HW
Department of Internal Medicine, Seoul National University, 28 Yongondong, Chongno-gu, Seoul 110-744, Republic of Korea.
Shin
Eun-Soon
ES
Lee
Jong-Eun
JE
Kwon
Hyouk-Soo
HS
Chun
Eunyoung
E
Kim
Sun-Sin
SS
Chang
Yoon-Seok
YS
Kim
Yoon-Keun
YK
Min
Kyung-Up
KU
Kim
You-Young
YY
Cho
Sang-Heon
SH
D000293:Adolescent; D002648:Child; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000453:epidemiology / Q000235:genetics*; D007723:Korea / Q000453:epidemiology; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012044:Regression Analysis; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*
D040301:Vascular Endothelial Growth Factor Receptor-2