Genetic factors of age-related macular degeneration

Abstract

Age-related macular degeneration (AMD) is a leading cause of blindness in the United States and developed countries. Although the etiology and pathogenesis of AMD remain unknown, a complex interaction of genetic and environmental factors is thought to exist. The incidence and progression of all of the features of AMD are known to increase significantly with age. The tendency for familial aggregation and the findings of gene variation association studies implicate a significant genetic component in the development of AMD. This review summarizes in detail the AMD-related genes identified by studies on genetically engineered and spontaneously gene-mutated (naturally mutated) animals, AMD chromosomal loci identified by linkage studies, AMD-related genes identified through studies of monogenic degenerative retinal diseases, and AMD-related gene variation identified by association studies.

An apolipoprotein E variant may protect against age‐related macular degeneration through cytokine regulation

“…To date, age, cigarette smoking, nutrition, and exposure to light have been identified as AMD risk factors [Age-Related Eye Disease Study Research Group, 2000Seddon et al, 2001;Husain et al, 2002;Hyman and Neborsky, 2002]. Various studies also indicate a significant genetic contribution to AMD risk [Tuo et al, 2004a]. For example, it has been reported that advanced AMD is more prevalent in Caucasian populations when compared with other races that possess higher levels of uveal pigmentation and skin melanin [Friedman et al, 1999;Age-Related Eye Disease Study Research Group, 2000].…”

“…The higher occurrence of AMD among monozygotic twins and first-degree relatives of AMD patients when compared with spouses and unrelated individuals also indicates a significant genetic component in AMD risk [Meyers et al, 1995;Seddon et al, 2005]. A few studies have been able to demonstrate an association between AMD and various single nucleotide polymorphisms (SNPs) [Tuo et al, 2004a;Edwards et al, 2005;Haines et al, 2005;Klein et al, 2005;Tuo et al, 2006]. Apolipoprotein E (ApoE) is a multiple function protein highly expressed in the liver, brain, and retina [Anderson et al, 2001;Ribalta et al, 2003].…”

A common haplotype in the complement regulatory gene factor H ( HF1/CFH ) predisposes individuals to age-related macular degeneration

“…AMD is characterized by a progressive loss of central vision attributable to degenerative and neovascular changes that occur at the interface between the neural retina and the underlying choroid. At this location are the retinal photoreceptors, the retinal pigmented epithelium (RPE), a basement membrane complex known as Bruch's membrane (BM) and a network of choroidal capillaries.The prevailing view is that AMD is a complex disorder stemming from the interaction of multiple genetic and environmental risk factors (3,4). Familial aggregation studies indicate that a genetic contribution can be identified in up to 25% of the cases (5).…”

“…The prevailing view is that AMD is a complex disorder stemming from the interaction of multiple genetic and environmental risk factors (3,4). Familial aggregation studies indicate that a genetic contribution can be identified in up to 25% of the cases (5).…”

“…A recent study suggests a minor association with Fibl5 (10), although this has yet to be confirmed. Genome-wide linkage analyses (4,11) have linked one AMD phenotype (ARMD1; MIM 603075) to chromosomal region 1q25-q31 (12). Fibl6 has been tentatively identified as the causal gene (13), although it does not account for a significant disease load (14,15).…”