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.