Abstract
Purpose :
To assess whether genotypes at two major loci associated with age-related macular degeneration (AMD), complement factor H (CFH) or age-related maculopathy susceptibility 2 (ARMS) interact with the response to oral nutrients for the treatment of AMD in a clinical trial, the Age-Related Eye Disease Study 2 (AREDS2).
Methods :
AREDS2 participants (n=4203) who had bilateral intermediate AMD (large drusen) or late AMD in 1 eye were randomly assigned to lutein/zeaxanthin, omega-3 fatty acids (DHA and EPA), low or high doses of zinc (25 mg vs. 80 mg). At baseline and annual study visits, history of treatment for late AMD and fundus photographs were obtained to evaluate for progression to late AMD. The outcome was late AMD, which was further evaluated for either geographic atrophy (GA) or neovascular AMD. Mixed effect Cox regression models using both eyes were conducted adjusting for age, sex, education level, and smoking history.
Results :
1732 participants had complete data including the genetic information. SNPs rs1061170 in the CFH gene and rs10490924 in the ARMS2 gene were evaluated. The participants (median age (SE): 72.5 y (7.8), 58.8% female, 97.1% white) were followed for a median of 6.5 years. These genetic variants in CFH and ARMS2 were found to increase the risk of progression. The test of interaction for each of the treatments with lutein and zeaxanthin, omega3-fatty acids, and varying dosage of zinc show no statistically significant interaction of the SNPs on the response to the oral supplements (see Table).
Conclusions :
There was no interaction of the response to any of the nutrient supplements with the known genetic SNPs that are associated with increased risk of progression to late AMD, including GA and neovascular AMD in AREDS2. Because only approximately half of our participants had genetic testing we may be limited in our power to truly evaluate for interaction. However, previous studies of genetic interactions in the first AREDS found that there were similar responses to the nutrient supplements, regardless of genetic factors.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.