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

Abstract

Background: Atopy is considered to be a complex genetic trait and do not follow a simple Mendelian pattern of heritance. It is now well recognized that gene-gene interactions are important in complex genetic disease.

Methods: A total of 2,055 ethnically identical subjects aged from 10 to 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 allergen. We analyzed gene to gene interactions among 12 polymorphic loci in the 7 candidate genes of atopy using 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 tumor necrosis factor α (TNF) on the risk of atopy, with a cross-validation consistency of 10 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 significant higher risk of atopy [OR (95%CI) = 2.23 (1.48-3.57)].

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