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

Mol Vis. 2009 Dec 10;15:2710-9.


Purpose: Genetic factors influence an individual's risk for developing neovascular age-related macular degeneration (AMD), a leading cause of irreversible blindness. Previous studies on the potential genetic link between AMD and vascular endothelial growth factor (VEGF), a key regulator of angiogenesis and vascular permeability, have yielded conflicting results. In the present case-control association study, we aimed to determine whether VEGF or its main receptor tyrosine kinase VEGFR-2 is genetically associated with neovascular AMD.

Methods: A total of 515 Caucasian patients with neovascular AMD and 253 ethically-matched controls were genotyped for polymorphisms in the VEGFA and VEGFR-2 genes. A tagging single nucleotide polymorphism (tSNP) approach was employed to cover each gene plus two kilobases on each side, spanning the promoter and 3' untranslated regions. SNPs with a minimum allele frequency of 10% were covered by seven tSNPs in VEGFA and 20 tSNPs in VEGFR-2. Two VEGFA SNPs previously linked with AMD, rs1413711 and rs3025039, were also analyzed.

Results: The 29 VEGFA and VEGFR-2 SNPs analyzed in our cohort demonstrated no significant association with neovascular AMD. A single rare haplotype in the VEGFR-2 gene was associated with the presence of neovascular AMD (p=0.034).

Conclusions: This study is the first to investigate the association of VEGFR-2 polymorphisms with AMD and evaluates VEGFA genetic variants in the largest neovascular AMD cohort to date. Despite the angiogenic and permeability-enhancing effects of VEGF/VEGFR-2 signaling, we found minimal evidence of a significant link between polymorphisms in the VEGFA and VEGFR-2 genes and neovascular AMD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Haplotypes / genetics
  • Humans
  • Linkage Disequilibrium / genetics
  • Macular Degeneration / complications*
  • Macular Degeneration / genetics*
  • Neovascularization, Pathologic / complications*
  • Neovascularization, Pathologic / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Vascular Endothelial Growth Factor A / genetics*
  • Vascular Endothelial Growth Factor Receptor-2 / genetics*


  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-2