Purchase this article with an account.
Robert F. Mullins, John H. Fingert, Micaela N. Johnson, James C. Folk, Edwin M. Stone; Evaluation Of Morphologic Features Of AMD Related To ARMS2 A69S Genotype. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1229.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Age-related macular degeneration (AMD) is a common disease with strong genetic risk factors, including the chromosome 10 ARMS2/HTRA1 locus. In the current study we investigated the impact of a common AMD risk allele, A69S in the ARMS2 gene, on a series of morphological features we and others have previously shown to be associated with AMD.
DNA samples from human donor eyes were genotyped at the ARMS2 SNP rs10490924 with a Taqman assay. Histological samples of human donor maculae were evaluated for choriocapillaris vascular density, drusen cross sectional area, choroidal CD45+ leukocytes, and number of ghost capillaries. Morphological features were related to ARMS2 genotypes in a small set of donors homozygous for the low risk allele (n=10) compared to donors with at least one copy of the high risk allele (n=11) using a two sample t-test.
Donor eyes with one or more high risk allele showed a trend toward a lower choriocapillaris density, increased drusen cross sectional area and increased number of ghost vessels; however none of these measurements reached statistical significance (p>0.05). In contrast, choroidal leukocyte density was on average 2-fold higher in the donors with at least one high risk allele (p value = 0.013 uncorrected for multiple measures).
Although several AMD risk alleles have been identified, the mechanism(s) through which these variants predispose an individual toward developing AMD are less well understood. Evaluating human donor eyes with known genotypes offers an opportunity to explore these mechanistic questions. This study suggests that the A69S ARMS2 variant may directly or indirectly affect inflammatory processes in aging eyes, including leukocyte recruitment or activation in AMD. Studies with larger sample size will be required to verify these preliminary findings.
This PDF is available to Subscribers Only