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Frances Wu, Ling Zhao, Wenting Wu, Hongrong Luo, Cindy Wen, Nicole Sfeir, Sherrina Patel, Henry Alexander Ferreyra, Michael Henry Goldbaum, Kang Zhang; Risk Prediction for Age-Related Macular Degeneration Using Genetic and Environmental Factors. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2232.
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To determine the individual and composite effects of genetic factors and smoking on the development of age-related macular degeneration (AMD), including the early form of AMD, which is characterized by the presence of confluent drusen in the retina, as well as the advanced forms of AMD, which include geographic atrophy (GA) and choroidal neovascularization (CNV).
DNA samples from 522 patients without AMD, 239 patients with confluent drusen, 271 patients with GA, and 1159 patients with CNV were analyzed for four genetic variants known to be associated with advanced AMD. Patients were also asked about their smoking status. Logistic regression was performed to generate a predictive model for AMD risk, and odds ratios were calculated based on individual and composite factors.
Odds ratios (ORs) for CNV were 5.26 (95% CI: 3.51-8.13) for HTRA1/ARMS2 rs10490924 TT, 2.15 (95% CI: 1.41-3.28) for CFH rs1061170 CC, 3.71 (95% CI: 2.31-6.00) for CFH rs2274700 CC, and 1.33 (95% CI: 1.05-1.68) for C3 rs2330199 CG when compared to individual reference genotypes. Smoking status alone was associated with an OR for CNV of 1.55 (95% CI: 1.24-1.95). ORs for GA were 3.85 (95% CI: 2.21-6.79) for HTRA1/ARMS2 rs10490924 TT, 1.89 (95% CI: 1.07-3.38) for CFH rs1061170 CC, 6.83 (95% CI: 3.10-16.21) for CFH rs2274700 CC, and 2.97 (95% CI: 1.61-5.52) for C3 rs2330199 GG when compared to individual reference genotypes. Smoking status alone was not associated with an increased risk of GA. The composite effect of all four genotypes combined with smoking was significant for CNV (p < 2*10-16), GA (p < 2*10-16) and drusen (p = 8.1*10-12). For smokers carrying a minimum of six out of eight possible risk alleles, the OR for CNV was 15.83 (95% CI: 6.06-45.19), and the OR for GA was 15.39 (95% CI: 3.47-110.84). For smokers carrying five risk alleles, the OR for drusen was 6.97 (95% CI: 2.13-27.86).
Combined genetic and environmental factors influence the risk of AMD significantly. CFH rs2274700 and C3 rs2330199 conferred greater risk for GA than for CNV. Because the onset of AMD can be insidious, it is important to develop predictive models to target high-risk individuals. Monitoring and early interventions may improve clinical outcomes in these patients.
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