Polymorphisms in the VEGFA and VEGFR-2 genes and neovascular age-related macular degeneration

摘要

Purpose: Genetic factors influence anindividual’s risk for developing neovascular age-related maculardegeneration (AMD), a leading cause of irreversible blindness. Previousstudies on the potential genetic link between AMD and vascularendothelial growth factor (VEGF), a key regulator of angiogenesis andvascular permeability, have yielded conflicting results. In the presentcase-control association study, we aimed to determine whether VEGF orits main receptor tyrosine kinase VEGFR-2 is genetically associatedwith neovascular AMD. Methods: A total of 515 Caucasianpatients with neovascular AMD and 253 ethically-matched controls weregenotyped for polymorphisms in the VEGFA and VEGFR-2genes. A tagging single nucleotide polymorphism (tSNP) approach wasemployed to cover each gene plus two kilobases on each side, spanningthe promoter and 3′ untranslated regions. SNPs with a minimum allelefrequency of 10% were covered by seven tSNPs in VEGFA and 20tSNPs in VEGFR-2. Two VEGFA SNPs previously linked withAMD, rs1413711and rs3025039,were also analyzed. Results: The 29 VEGFA and VEGFR-2SNPs analyzed in our cohort demonstrated no significant associationwith neovascular AMD. A single rare haplotype in the VEGFR-2gene was associated with the presence of neovascular AMD (p=0.034). Conclusions: This study is the first toinvestigate the association of VEGFR-2 polymorphisms with AMDand evaluates VEGFA genetic variants in the largest neovascularAMD cohort to date. Despite the angiogenic and permeability-enhancingeffects of VEGF/VEGFR-2 signaling, we found minimal evidence of asignificant link between polymorphisms in the VEGFA and VEGFR-2genes and neovascular AMD.