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Acta Ophthalmol. 2014 Dec;92(8):745-8. doi: 10.1111/aos.12437. Epub 2014 May 22.

Environmental and genetic risk factors for retinal angiomatous proliferation.

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Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany.



To identify genetic and environmental risk factors in patients with retinal angiomatous proliferation (RAP), a clinical subtype of age-related macular degeneration (AMD).


In this case-control study, 108 AMD cases with RAP, 258 AMD patients with choroidal neovascularization (CNV) without RAP and 443 healthy controls were evaluated. Single nucleotide polymorphisms in age-related maculopathy susceptibility 2 (ARMS2) and complement factor H (CFH) and various environmental risk factors were analysed. Statistical analysis was performed by univariate and multivariate regression analysis.


High age, female sex and genetic variants in CFH and ARMS2 were identified as risk factors for developing any CNV. In RAP patients, arterial hypertension was also identified as a risk factor (OR 2.39; p = 0.0005). Compared with the 'non-RAP' CNV group, the association with high age (OR 1.05; p = 0.008) and arterial hypertension (OR 1.82; p = 0.02) was significantly higher in RAP patients, while the association with CFH risk alleles (homozygous OR 0.40; p = 0.003) was significantly lower, which was confirmed in a multivariate analysis (OR 0.41; p = 0.03 for the heterozygous risk allele and OR 0.38; p = 0.03 for the homozygous risk allele).


The association with the CFH Y402 risk allele was less pronounced in RAP patients than in 'non-RAP' CNV patients, while the association with high age and arterial hypertension appeared to be stronger. These findings stress the importance of detailed phenotyping in AMD to identify homogeneous AMD subtypes and their different risk factors and disease mechanisms.


ARMS2; CFH; age-related macular degeneration; hypertension; retinal angiomatous proliferation; risk factor

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