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Paul R Healey, Jie Jin Wang, George Burlutsky, Caroline C W Klaver, Gabrielle HS Buitendijk, Victoria Flood, Andrew JR White, Gerald Liew, Paulus T V M De Jong, Paul Mitchell; CFH, ARMS2, Dietary Zinc and Age-Related Macular Degeneration; a Population-based Assessment. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2574. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the effect of CFH and ARMS2 risk alleles on the relationship between dietary zinc intake and incident late-stage age-related macular degeneration (AMD) in well-defined, European-derived, population-based cohorts.
Participants from the Blue Mountains Eye Study (BMES) and Rotterdam Study (RS) had dietary zinc intake assessed by food frequency questionnaires and genotyping performed using an Illumina Human 670-Quadv1 custom array and TaqMan assays. The cumulative 15-year probability of late-stage AMD was calculated using logistic regression analysis adjusting for age and smoking and after testing for interactions. Zinc intake was assessed both as a categorical and continuous variable. Participants were divided into four genotype groups according to CFH (C) and ARMS2 (A) risk allele number (0, 1 or 2); Group 1 (C01, A0), Group 2 (C2, A0), Group 3 (C01, A12), Group 4 (C2, A12).
A total of 5246 participants were studied. The frequencies of Groups 1, 2, 3 and 4 were 53.0%, 8.7%, 32.9%, 5.4% respectively in the BMES and 55.1%, 7.7%, 32.5%, 4.8% respectively in the RS. Mean zinc intake was 12mg/day and 10.6mg/day in the two population respectively, and not significantly different among genotype groups. The overall incidence of AMD was 5.0% and varied by genotype group, 2.7%, 8.2%, 6.2%, and 19.7% in Groups 1, 2, 3 and 4 respectively in a combined two-population dataset. After adjusting for age, smoking and zinc intake, AMD was 3.0, 2.5 and 11.8 times more likely in Groups 2, 3 and 4 compared with Group 1. Zinc intake was associated with a substantially reduced AMD incidence in Group 4 (per mg/day increase, OR 0.8, 95% CI 0.7-0.9, p=0.0042). Compared with the lowest quartile of zinc intake (7.5mg/day), those consuming the highest quartile (15.3mg/day) were 81% less likely to develop AMD (OR 0.19, 95% CI 0.06-0.64, p=0.0074). No statistically significant increase or decrease in AMD risk associated with dietary zinc intake levels was found in the other genotype groups.
The frequencies of CFH/ARMS2 risk genotypes vary in European-derived populations with the lowest risk genotype found in over 50% of populations. In the genotype group at highest risk of AMD, increased dietary zinc intake was associated with a substantial reduction in AMD risk, in a dose-dependent manner.
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