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A. Farwick, D. Pauleikhoff, M. Stoll, H. W. Hense; Variants of the CFH Gene, Smoking and the Risk of Early and Late Age-Related Maculopathy. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1154.
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Numerous genetic variants within the Complement Factor H (CFH) gene have been shown to be associated with established age-related macular degeneration (AMD), i.e. geographic atrophy (GA) or neovascularisation (CNV). Less is known about the genetic associations with maculopathy (ARM), i.e. drusen and/or pigment abnormalities, the interaction between the different variants on risk, and about potential environmental modifiers.
We investigated these questions in a large cohort of patients with ARM (N = 440), AMD (n = 278) and controls (n = 177) from the Muenster Aging and Retina Study (MARS) in which all phenotypes were assigned after standardised grading of digital fundus photos. We genotyped all patients for CFH-SNPs: rs1061170, rs2274700 and rs1292487.
We observed that both, rs10611770 and rs2274700, significantly increased the risk of ARM in heterozygous (each OR = 1.9) and homozygous patients (OR 5.6 and 4.3, respectively). The AMD risk was substantially raised: OR = 2.0 and 1.9 for heterozygous 6.9 and 5.9, resp., in homozygous patients. Both SNPs were more strongly associated with CNV than GA, and only for CNV we found a significant risk increment due to smoking (homozygous smokers OR = 7.9 and 13.7, resp.; p < 0.0001). Furthermore, patients homozygous for both risk variants (30% of ARM and 35.4% of AMD) showed an 8.2-fold risk of ARM and 10.9 times higher risk of AMD compared to people carrying only the wild-types. By contrast, rs1292487 showed a significant and clear protective effect on both ARM and AMD (ORs from 0.73 to 0.19), in particular among the homozygous.
Our results indicate that several CFH variants are associated with early and late disorders of the ageing macula. The association is particularly pronounced for the occurrence of CNV, and smoking seems to confer substantial risk increments. The two risk variants act in a synergistical way and generate a cumulative risk of AMD. However, there are also less common variants which confer protection against the ageing disorders of the macula.
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