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Epidemiology
Multilocus analysis of atopy in Korean children using multifactor-dimensionality reduction
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  1. Heung-Woo Park1,
  2. Eun-Soon Shin2,
  3. Jong-Eun Lee2,
  4. Hyouk-Soo Kwon1,
  5. Eunyoung Chun1,
  6. Sun-Sin Kim1,
  7. Yoon-Seok Chang1,
  8. Yoon-Keun Kim1,3,
  9. Kyung-Up Min1,
  10. You-Young Kim1,
  11. Sang-Heon Cho1
  1. 1Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
  2. 2DNA Link, Seoul, Republic of Korea
  3. 3Department of Life Science, Pohang University of Science and Technology, Pohang, Republic of Korea
  1. 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

Abstract

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)α 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.

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

https://doi.org/10.1136/thx.2006.065482

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