Association between genetic variations of vascular endothelial growth factor receptor 2 and atopy in the Korean population

Abstract

Background: Vascular endothelial growth factor (VEGF) has been suggested to be a key mediator in the development of atopy and T(H)2 inflammation. Objective: We sought to evaluate the effects of variations in the gene coding VEGF receptor (VEGFR) 2 on intermediate phenotypes of asthma in the Korean population. Methods: A cohort of 2055 children and adolescents responded to a questionnaire concerning asthma symptoms and risk factors and underwent methacholine bronchial challenge and skin tests. The VEGFR2 gene, including the promoter area, was sequenced on 24 healthy subjects to discover informative single nucleotide polymorphisms (SNPs; minor allele frequency >2%). After haplotype reconstruction, 4 tagging SNPs (IVS6+54A>G, +889G>A, +1416T>A, and IVS25-92G>A) were scored. These SNPs were also scored in 480 adult asthmatic patients to verify the above genetic association study. Results: The prevalence of atopy was associated with a single SNP (+889G>A) of VFGFR2 with borderline significance (P =.048; relative risk, 1.13; 95% CI, 1.00-1.28). However, haplotype analysis showed that the atopy prevalence was strongly associated with a haplotype (AGAG) of VEGFR2 (P =.002; relative risk, 1.25; 95% CI, 1.09-1.42). As for airway hyperresponsiveness., neither individual SNPs nor haplotypes were found to be associated. Interestingly, the significant association was also found between atopy and the AGAG haplotype among adult asthmatic patients (P =.008; odds ratio, 1.66; 95% CI, 1.14-2.44). Conclusions: The present study demonstrated that genetic variations of VEGFR2 are significantly associated with atopy in the Korean population.