Associations of Complement Factor H and Smoking with Early Age-Related Macular Degeneration: The ALIENOR Study

PURPOSE. To assess the associations of complement factor H (CFH) Y402H polymorphism and smoking with specific features of early AMD (type, location, and area). METHODS. The ALIENOR study is a population-based study of age-related eye diseases in 963 residents of Bordeaux (France), aged 73 years or more. AMD features were graded from non-mydriatic color retinal photographs. CFH Y402H was genotyped by using DNA extracted from blood. Statistical analyses included 796 subjects with complete data. RESULTS. CFH CC genotype was strongly associated with late neovascular AMD (OR, 6.0; 95% confidence interval [CI], 1.5-23.5) but not with late atrophic AMD (OR, 0.9; 95% CI, 0.2-4.3). Among early characteristics, it was associated with central soft drusen (within 500 mu m of the fovea), whether of intermediate (63-125 mu m; OR, 2.7; 95% CI, 1.5-4.8), or large (>125 mu m; OR, 5.9; 95% CI, 2.2-15.7) size, but not with pericentral soft drusen (500-3000 mu m from the fovea). It was also strongly associated with a large central area of soft drusen (OR, 5.7; 95% CI, 1.7-19.2). Similarly, heavy smoking (>20 pack-years) was strongly associated with central large drusen (OR, 3.9; 95% CI, 1.6-9.6) and a large central area of drusen (OR, 3.5; 95% CI, 1.2-10.0), but not with pericentral soft drusen. By contrast, both CFH CC and smoking tended to be more strongly associated with pericentral pigmentary abnormalities. CONCLUSIONS. Location of abnormalities, together with type and area, may prove useful for the identification of subjects at high risk for late AMD. (Invest Ophthalmol Vis Sci. 2011;52:5955-5962) DOI: 10.1167/iovs.10-6235