Distinct association of genetic variations of vascular endothelial growth factor, transforming growth factor-β, and fibroblast growth factor receptors with atopy and airway hyperresponsiveness

Background: Recent studies showed that high levels of transforming growth factor (TGF)-beta 1 in the airways reduced airway responsiveness, which was reversed in conditions of basic fibroblast growth factor (FGF2) deficiency, whereas high levels of vascular endothelial growth factor (VEGF) enhanced airway sensitization to allergens and airway hyperresponsiveness (AHR). Objective: We investigated the effect of single-nucleotide polymorphisms (SNPs) in the VEGF, TGF-beta 1, and FGF2 receptors on the expression of atopy and AHR in the general population. Methods: Atopy and AHR were evaluated in a cohort of 2055 children and adolescents. Direct sequencing was used to identify informative SNPs (minor allele frequency > 5%) in the receptors of candidate genes. Tagging SNPs were scored using the high-throughput single-base pair extension method, and the statistical significance of these scores was assessed via haplotype analysis. Results: Informative SNPs were identified for VEGF receptors 1 (Flt-1); TGF-beta receptor 3 (TGFBR3); and FGR receptors 1, 2, and 4 (FGFR1, FGFR2, and FGFR4), and 13 tagging SNPs were scored in the cohort. Atopy was significantly associated with haplotypes of TGFBR3, FGFR1, and FGFR2. Meanwhile, AHR was significantly associated with haplotypes of Flt-1, FGFR1, and FGFR4. However, atopy was not associated with genetic variations of Flt-1 and FGFR4, whereas AHR not associated with TGFBR3 and FGFR2. Conclusion: The expression of atopy and AHR is distinctly associated with genetic variations in VEGF, TGF-beta 1, and FGFR in the Korean population.