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

• Published in: Thorax 2007-03, Vol.62 (3), p.265-269
• Main Authors: Park, Heung-Woo, Shin, Eun-Soon, Lee, Jong-Eun, Kwon, Hyouk-Soo, Chun, Eunyoung, Kim, Sun-Sin, Chang, Yoon-Seok, Kim, Yoon-Keun, Min, Kyung-Up, Kim, You-Young, Cho, Sang-Heon
• Format: Article
• Language: English
• Subjects: Adolescent; Allergies; Antigens; Asthma; Biological and medical sciences; Child; Cytokines; Epidemiology; Female; Gene Frequency; Genes; Genotype; Heart attacks; Humans; Hypersensitivity, Immediate - epidemiology; Hypersensitivity, Immediate - genetics; KDR; kinase insert domain-containing receptor; Korea - epidemiology; Logistics; Male; MDR; Medical sciences; multifactor-dimensionality reduction; Pneumology; Polymorphism, Single Nucleotide - genetics; Regression Analysis; single-nucleotide polymorphism; SNP; Studies; TNF; Tumor necrosis factor-TNF; tumour necrosis factor; vascular endothelial growth factor; Vascular Endothelial Growth Factor Receptor-2 - genetics; VEGF
• ISSN: 0040-6376; 1468-3296
• DOI: 10.1136/thx.2006.065482

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.