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Published Online First: 22 November 2006. doi:10.1136/thx.2006.065482
Thorax 2007;62:265-269
Copyright © 2007 BMJ Publishing Group Ltd & British Thoracic Society.

EPIDEMIOLOGY

Multilocus analysis of atopy in Korean children using multifactor-dimensionality reduction

Heung-Woo Park1, Eun-Soon Shin2, Jong-Eun Lee2, Hyouk-Soo Kwon1, Eunyoung Chun1, Sun-Sin Kim1, Yoon-Seok Chang1, Yoon-Keun Kim1,3, Kyung-Up Min1, You-Young Kim1, Sang-Heon Cho1

1 Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
2 DNA Link, Seoul, Republic of Korea
3 Department of Life Science, Pohang University of Science and Technology, Pohang, Republic of Korea

Correspondence to:
Dr S-H Cho
Department of Internal Medicine, Seoul National University, 28 Yongondong, Chongno-gu, Seoul 110-744, Republic of Korea; shcho{at}plaza.snu.ac.kr

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.

Aim: 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).

Conclusion: KDR and TNF may synergistically influence the development of atopy through gene–gene interaction in Korean children and adolescents.

Abbreviations: KDR, kinase insert domain-containing receptor; MDR, multifactor-dimensionality reduction; SNP, single-nucleotide polymorphism; TNF, tumour necrosis factor; VEGF, vascular endothelial growth factor


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