Genetics and genetic testing for age-related macular degeneration

Abstract

Considerable advances have been made in our understanding of age-related macular degeneration (AMD) genetics over the past decade. The genetic associations discovered to date are estimated to account for approximately half of AMD heritability, and functional studies of these variants have revealed new insights into disease pathogenesis, leading to the development of potential novel therapies. There is furthermore growing interest in genetic testing for predicting an individual's risk of AMD and offering personalised preventive or therapeutic treatments. We review the progress made so far in AMD genetics and discuss the possible applications for genetic testing.

Epigenetics in age-related macular degeneration: new discoveries and future perspectives

“…C3 has been shown to result in reduced binding to CFH and reduced complement regulation leading to increased membrane attack complex (MAC) deposition at the choriocapillaris [37,38]. The association of AMD pathogenesis with chromosome 10q26, which surrounds ARMS2 and HTRA1, has also been demonstrated in many studies although the debate is ongoing as to the causal allele and underlying pathogenic mechanism [39].…”

Das Komplementsystem: von den Grundlagen zur klinischen Bedeutung

“…In einer kürzlich durch-geführten, genomweiten Assoziationsstudie (GWAS) wurden 52 häufige und seltene Genvarianten identifiziert, die unabhängig voneinander mit AMD assoziiert sind [108]. Unter ihnen befindet sich mehr als ein Drittel (19/52) in oder in der Nähe eines Komplementgens [103,105,108,109]. Insbesondere Varianten der Komplementgene CFH, CFI, C2/CFB, C3, C9, CD55 und Vitronectin (VTN) wurden mit einem erhöhten Risiko für die Entwicklung von AMD in Verbindung gebracht [108, 110 -112].…”

Sorsby fundus dystrophy: Insights from the past and looking to the future

“…This observation has led to the hypothesis that rare TIMP3 protein-altering variants together with alleles at other AMD risk loci contribute to AMD development (Fritsche et al, 2016). A retrospective, observational case series has recently shown that patients initially diagnosed with neovascular AMD carry the SFD-associated p.(Ser38Cys)-TIMP3 mutation (Warwick & Lotery, 2017). SFD phenotypic expressivity varies considerably including large intra-and interfamilial variability in the age of onset of visual symptoms (Gliem, Muller, Mangold, Holz, et al, 2015).…”