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Emily Y Chew, Michael L Klein, Traci E Clemons, Elvira Agron, Anand Swaroop, Rinki Ratna Priya, The Age-Related Eye Disease Study Research Group; Interaction of Genotypic Risks and the AREDS Supplements for Progression to Late Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4572.
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To assess interaction between genotype, Age-Related Eye Disease Study (AREDS) supplements and their components, and progression to late age-related macular degeneration (AMD).
Using an expanded AREDS cohort (N=1425), we reanalyzed initial results (N=876) of CFH (Y402H) and ARMS2 (A69S ) interaction with AREDS supplements in participants for whom supplements are clinically indicated to reduce progression to late AMD. These comprised participants with large drusen and/or late AMD in one eye. We also used a Cox proportional hazards model to assess treatment interactions between variants in these 2 loci using 9 genotypic subgroups, and progression to late AMD. The SNPs evaluated were CFH rs1061170, ARMS2 rs10490924.
We found that increasing the sample size did not provide statistically significant evidence for genetic interaction with AREDS supplements or their components. The overall Cox regression interaction term was P=0.77. Analyses with these and additional variants were conducted for each of the 9 genotypic subgroups to assess the treatment specific estimates of the progression to late AMD. The accompanying confidence intervals and p-values were calculated. Results showed wide, overlapping 95% confidence intervals and no-statistically significant evidence for a genetic by treatment interaction using antioxidants and zinc, antioxidants alone, or zinc alone.
We found a lack of statistically significant evidence for interaction between genetic factors and AREDS supplements or their components to justify changing the current clinical use of the AREDS formulation in patients with increased risk of developing late AMD. We recommend the continued use of the current AREDS formulation consisting of both antioxidant vitamins and zinc.
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