The Arms2 A69s Variant and Bilateral Advanced Age-Related Macular Degeneration

Abstract

Purpose To identify genetic associations between specific risk genes and bilateral advanced age-related macular degeneration (AMD) in a retrospective, observational case series of 1,003 patients: 173 patients with geographic atrophy in at least 1 eye and 830 patients with choroidal neovascularization in at least 1 eye. Methods Patients underwent clinical examination and fundus photography. The images were subsequently graded using a modified grading system adapted from the Age-Related Eye Disease Study. Genetic analysis was performed to identify genotypes at 4 AMD-associated variants (ARMS2 A69S, CFH Y402H, C3 R102G, and CFB R32Q) in these patients. Results There were no statistically significant relationships between clinical findings and genotypes at CFH, C3, and CFB. The genotype at ARMS2 correlated with bilateral advanced AMD using a variety of comparisons: unilateral geographic atrophy versus bilateral geographic atrophy (P = 0.08), unilateral choroidal neovascularization versus bilateral choroidal neovascularization (P = 9.0 × 10 −8), and unilateral late AMD versus bilateral late AMD (P = 5.9 × 10 −8). Conclusion In this series, in patients with geographic atrophy or choroidal neovascularization in at least 1 eye, the ARMS2 A69S substitution strongly associated with geographic atrophy or choroidal neovascularization in the fellow eye. The ARMS2 A69S substitution may serve as a marker for bilateral advanced AMD.

Risk characteristics of the combined geographic atrophy and choroidal neovascularisation phenotype in age-related macular degeneration

“…However, they have a similar genetic and environmental risk profile [5][6][7][8][9][10][11][12][13][14] and may be two possible advanced manifestations of a single disease process whose outcome is controlled by a balance of factors yet to be determined. The combined GA/ CNV form could then represent the outcome when all these factors are involved.…”

Patient-specific induced pluripotent stem cells (iPSCs) for the study and treatment of retinal degenerative diseases

“…Although the notion that AMD has a strong genetic component was advocated as early as the 1970s (Davanger and Evensen, 1971;Gass, 1973;Jiang et al, 2002;Snippert et al, 2010), our understanding of the biological mechanisms through which specific genetic loci contribute to the development and progression of AMD is still poorly understood. Genome wide association studies of AMD identified two loci on chromosomes 1 and 10 that are highlyassociated with disease risk (Edwards et al, 2005;Haines et al, 2005;Jakobsdottir et al, 2005;Klein et al, 2005;Rivera et al, 2005;Schwartz et al, 2012b;Yamanaka and Takahashi, 2006;Zareparsi et al, 2005). The risk associated with the chromosome 1q locus is predominantly due to a haplotype that harbors a missense mutation (Tyr402His) in the complement factor H (CFH) gene (Avilion et al, 2003;Chambers et al, 2003;Hageman et al, 2006;Mitsui et al, 2003;Nichols et al, 1998;Zhang et al, 2008).…”

Stem Cells as Tools for Studying the Genetics of Inherited Retinal Degenerations

“…Although the notion that AMD has a strong genetic component was advocated as early as the 1970s (Gass 1973), our understanding of the biological mechanisms through which specific genetic loci contribute to the development and progression of AMD is still rather poorly understood. Genome wide association studies of AMD identified two loci on chromosomes 1 and 10 that are highly associated with disease risk (Edwards et al 2005;Haines et al 2005;Jakobsdottir et al 2005;Klein et al 2005;Rivera et al 2005;Zareparsi et al 2005;Schwartz et al 2012). The risk associated with the chromosome 1q locus is predominantly because of a haplotype that harbors a missense mutation in the complement factor H (CFH) gene (Tyr402His) (Hageman et al 2006;Zhang et al 2008).…”