Abstract

DO.13.01

Genetics of age-related macular degeneration – new perspectives

Scholl H. P. N.
Universitäts-Augenklinik Bonn

Age-related macular degeneration (AMD) is a genetically complex disorder affecting the photoreceptor-RPE-Bruch’s membrane-choriocapillaris complex. Family and twin studies have shown that the susceptibility for disease is genetically influenced. The heritability has been estimated to be up to 71%. Linkage and association studies have identified several chromosomal regions that are likely to contain susceptibility loci. The strongest evidence for an AMD susceptibility locus was found on chromosome 1q31 and 10q26. Variants in the complement factor H gene have been shown by several independent studies to be associated with an increased risk for AMD in Caucasian populations. These findings imply that the innate immune system may play a significant role in AMD pathogenesis. The LOC387715/HTRA1 locus within 10q26 has been identified as second major locus contributing to AMD pathogenesis. The two late forms of AMD, choroidal neovascularization and geographic atrophy, have not been found to be different in risk allele distribution. Variants within CFH and LOC387715/HTRA1 may contribute to the increased risk of advanced AMD largely or entirely through their impact on precursors, such as drusen and/or other RPE/Bruch’s membrane changes. Considering variants at CFH, LOC387715 and Factor B/Complement Component 2 (2-CFB), high-risk homozygotes at all three loci have a more than 250-fold greater risk compared to baseline. However, the identification of genetic factors has not resulted in therapeutic strategies to modify the disease so far and additional genetic and environmental factors are yet to be discovered in order to influence the onset and the progression of AMD.

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