An update on the genetics of age-related macular degeneration

[摘要] Age-related macular degeneration (AMD) is a genetically complexdisorder of the photoreceptor-RPE-Bruch's membrane-choriocapillariscomplex. Family and twin studies have shown that the susceptibility forthis disease is genetically influenced. The heritability has beenestimated to be up to 71%. Linkage and association studies haveidentified several chromosomal regions that are likely to containsusceptibility loci with strongest evidence found on chromosome 1q31 and10q26. Variants in the complement factor H (CFH) gene have been shown byseveral independent studies to be associated with an increased risk forAMD in Caucasian populations. These findings imply that the innateimmune system may play a significant role in AMD pathogenesis. TheLOC387715/HTRA1 locus within 10q26 has been identified as asecond major locus contributing to AMD pathogenesis. The two late formsof AMD, choroidal neovascularization and geographic atrophy, have notbeen found to be different in risk allele distribution. Variants withinCFH and LOC387715/HTRA1 may contribute to the increased riskof late AMD largely through their impact on precursors, such as drusenand/or other RPE/Bruch's membrane changes. Considering variants atCFH, LOC387715/HTRA1 and complement component 2-complementfactor B (C2-FB), high-risk homozygotes at all three loci may have a250-fold increased risk compared to baseline. However, theidentification of genetic factors has not resulted in therapeuticstrategies to modify the disease so far and additional genetic andenvironmental factors are yet to be discovered in order to influence theonset and the progression of AMD.

[学科分类] 生物化学/生物物理