VEGF polymorphisms are associated with neovascular age-related macular degeneration

Hum Mol Genet. 2006 Oct 1;15(19):2955-61. doi: 10.1093/hmg/ddl238. Epub 2006 Aug 29.


Age-related macular degeneration (AMD) is the most common cause of blindness in the elderly. Linkage has been shown to the vascular endothelial growth factor (VEGF) gene and ocular levels of VEGF are raised in individuals with the neovascular form of disease. To examine the role of VEGF further, we conducted a case-control study where 45 individuals with neovascular AMD and 94 age-matched controls were genotyped for 14 single nucleotide polymorphisms (SNPs) in the VEGF promoter and gene. The single SNP +674 CC genotype was significantly associated with AMD (OR=2.40, 95%CI 1.09-5.26, P=0.027). Haplotype analysis of SNPs +674, +4618, +5092, +9162 and +9512 revealed that CTCCT and TCACC were associated with AMD (OR=15.77, 95% CI 1.91-130.24, P=0.0161 and OR=9.95, 95%CI 3.22-30.74, P=0.000053, respectively). The haplotype TCACT was associated with the control group (P=0.0001832). Furthermore, haplotype analysis of promoter SNPs revealed that possession of the -460T, -417T, -172C, -165C, -160C, -152G, -141A, -116A, +405C haplotype was strongly associated with AMD (OR=18.24, 95%CI 2.25-148.25, P=0.0074). This is the most extensive analysis of the VEGF gene in AMD, demonstrating a clear association with the exudative form of disease, thereby creating the possibility for predictive testing. Smoking, high fat intake and hypertension are negative environmental risk factors in AMD, whereas increased consumption of dietary antioxidants can have a protective effect. Identification of those at risk in the population would allow individual counselling with lifestyle advice to reduce the risks of blindness. (Genbank accession nos M63971 and AF437895).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions
  • Aged
  • Base Sequence
  • Case-Control Studies
  • DNA Primers / genetics
  • Genotype
  • Haplotypes
  • Humans
  • Macular Degeneration / etiology
  • Macular Degeneration / genetics*
  • Macular Degeneration / prevention & control
  • Neovascularization, Pathologic / genetics*
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic
  • Risk Factors
  • Vascular Endothelial Growth Factor A / genetics*


  • 5' Untranslated Regions
  • DNA Primers
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A