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Xavier Subiras Rodriguez, Tina Schick, Aileen Berghold, Bernd Kirchhof, Anneke I den Hollander, Sascha Fauser, Sandra Liakopoulos; Genetic and environmental risk factors for extramacular drusen. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2630.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate genetic and environmental risk factors for extramacular drusen (EMD) in patients with and without age-related macular degeneration (AMD).
In this case-control study, 1148 individuals from a multicenter genetic database for AMD (EUGENDA) were included. Fundus photographs were analyzed for the presence of EMD (none; ≥10 EMD; ≥30 EMD). AMD staging was performed by trained graders. Evaluated risk factors included 41 non-genetic risk factors and 41 single nucleotide polymorphisms. Univariate regression analysis was performed after adjustment for AMD.
At least 10 EMD were present in 500 subjects. Of these, 299 cases had ≥30 EMD. 587 individuals showed no AMD, 277 had early or intermediate AMD and 284 had late AMD. Genetic associations with EMD were found for the homozygous risk variant of ARMS2 (rs10490924) (Odds ratio (OR)=2.51; 95% Confidence Interval (CI)=1.45-4.36; p=0.001); the heterozygous risk variants of ADAMTS9 (rs6795735) (OR=1.54; CI=1.11-2.14; p=0.01) and VEGFA (rs943080) (OR=1.48; CI= 1.01-2.15; p=0.04). Associations were also found for past sunlight exposure (≥8h/day outside: OR= 6.83; CI=1.37-34.19; p=0.02) and current sunlight exposure (≥8h/day outside: OR= 7.28; CI=1.37-38.60; p=0.02; 4-8h/day outside: OR=5.55; CI=1.11-27.59; p=0.04). Analysis of subjects with ≥30 EMD showed significant associations with homozygous risk variants of ARMS2 (OR= 2.10; CI=1.12-3.98; p=0.02) and CFHY402H (rs1061170) (OR= 1.86; CI=1.13-3.06; p=0.01), past sunlight exposure (≥8 h/day outside: OR=15.37; CI= 1.50-157.54; p= 0.02) and current sunlight exposure (≥8h/day outside: OR= 16.90; CI=1.44-198.33; p=0.02; 4-8h/day outside: OR= 11.34; CI=1.04-124,04; p=0.047). Additionally, heterozygous risk variants of CFH (rs12144939) (OR= 0.61; CI=0.40-0.92; p=0.02) and SLC16A8 (rs8135665) (OR=0.66; CI=0.45-0.98; p=0.04) showed significant associations.
After adjustment for AMD, associations with ≥10 EMD were found for ARMS2 and sunlight exposure, however not for CFHY402H. At least 30 EMD were additionally associated with the homozygous but not with the heterozygous risk polymorphism in CFHY402H. CFH (rs12144939) and SLC16A8 appeared to have protective effects in EMD development. Additional AMD-independent factors may be involved in the pathogenesis of EMD and further studies are required to evaluate these risk factors.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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