Vascular Endothelial Growth Factor (VEGF) Polymorphisms and Their Association With Age-Related Macular Degeneration

Abstract

Purpose:: Age-related macular degeneration (AMD) is the leading cause of severe visual loss in people over 50 years of age in the United States. Vascular endothelial growth factor (VEGF)-A has been found to play a major role in retinal and choroidal neovascularization. The use of anti-VEGF medications has become the standard treatment for neovascular AMD. Churchill and colleagues recently examined the association between neovascular AMD and VEGF and reported a signifiicant association with the SNP rs 1413711 and neovascular AMD. The purpose of this study is to evaluate the assocation of rs1413711 and neovascular AMD in a Utah cohort and investigate any association with different subtypes of AMD

Methods:: Patients with AMD at the University of Utah Moran Eye Center in Salt Lake City, Utah underwent dilated fundus examination and fluorescein angiography if needed. Based upon these findings patients were grouped into 3 different AMD subtypes: geographic atrophy, soft confluent drusen and neovascular AMD. Blood samples were collected after obtaining informed consent and genotyped with snapshot kits using a ABI 3130 sequencer. The allele frequencies of the SNP rs 1413711 were compared in cases and controls and with the different AMD subtypes. Statistical analysis was performed using the SPSS program, and p-values reported using Pearson’s chi-square.

Results:: 75 patients with geographic atrophy, 82 patients with soft confluent drusen, 292 patients with exudative AMD and 200 controls were genotyped. There was no significant assocation found between SNP rs 1413711 and neovascular AMD (p=0.252). Additionally, there was no assocation between the SNP rs1413711 and any of the other subtypes of AMD, including those patients with geographic atrophy (p=0.323 ) and soft confluent drusen (p=0.186).

Conclusions:: Churchill and colleagues found a significant association with SNP rs1413711 and neovascular AMD. However, our analysis showed no significiant association. There was also no association found in the geographic atrophy and soft confluent drusen groups. Additional analysis needs to be performed to investigate if any other SNPs in VEGF play a role in AMD. Genotyping of additional SNPs in VEGF is in progress and will be presented.

Keywords: age-related macular degeneration • clinical (human) or epidemiologic studies: risk factor assessment • gene screening