Purchase this article with an account.
James C. Folk, Michael D. Abramoff, Jason A. Orien, Mark A. Christopher, Todd E. Scheetz, Robert F. Mullins, Mari E. Eyestone, Jade S. East, Emily I. Schindler, Edwin M. Stone; Age-Related Macular Degeneration Risk Alleles and Response to Treatment with Anti-VEGF Agents. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5238.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
1. To compare the frequency of known risk alleles in a large population of patients with age-related macular degeneration (AMD) at Iowa to a normal control group. 2. To determine whether any of these risk alleles affect the response to anti-vascular endothelial growth factor (anti-VEGF) agents in patients with neovascular AMD.
A Fluidigm allele-specific array tested 44 genetic variants over 28 genes in AMD patients with category 3 or 4 AMD and normal controls with no drusen. Response to anti-VEGF agents was determined by outlining the areas of subretinal and intraretinal fluid on optical coherence tomography (OCT) and then calculating the difference between baseline, 3 months and 6 months. Visual acuity at 6 months was also used to determine response to treatment. Chi-squared analysis was used to test for genetic association of AMD diagnosis to the 44 genetic variations. Analysis of variance (ANOVA) was used to test for genetic association between the fluid and visual acuity measurements and the CFH and ARMS2 genetic variants in the anti-VEGF treated cohort. Because multiple genotype-phenotype hypotheses were tested, a Bonferroni correction was applied when assessing the statistical significance of the resulting p-values.
For the assessment of risk allele frequency, 782 patients with AMD and 331 normal control patients from the same clinic were tested with the following results demonstrating the significance of association of each allele with AMD, given in p-values: ARMS (A69S) 3x10-23, HTRA1 2x10-16, CFH (Y402H) 2x10-20, PLEKHA1 1x10-10, C2 5x10-8, APOE (R176C) 7x10-4. Genes that were not statistically associated with AMD in this study included: ABCA4, CFB, CFI, C7, CST3, CX3CR1, ELOVL4, ERCC6, IL8, MAP2, MBL2, MMP9, ND2, ND4, PON1, SERPING1, TLR3, TLR4, and VEGFA. In analysis of the effect of risk alleles on treatment response to anti-VEGF agents, no statistically significant difference was seen between risk ARMS2 and CFH alleles and controls with respect to change in visual acuity or presence of fluid on OCT after 6 months of treatment.
The ARMS2 risk allele had the highest association with AMD in our Iowa population and deserves further study since it appears to be as important as complement factor genes in AMD.
This PDF is available to Subscribers Only