Affiliations: [a] The Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| [b]
Tennessee Retina PC, Nashville, TN, USA
| [c]
CRF Health Outcomes Research Consulting, Waterloo, Ontario, Canada
| [d] Faculty of Medicine, Division of Hematology, University of Toronto, Toronto, Canada
Correspondence:
[*]
Correspondence to: Brent Zanke, MD, PhD, Arctic Medical Laboratories, 801 Broadway Avenue NW, Suite 303, Grand Rapids, MI, 49504, USA. Tel.: +1 866 964 5182. E-mail: bzanke@arcticdx.com.
Abstract: Background:An interaction between genetic variants in complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) and high-dose zinc supplementation on progression to advanced age-related macular degeneration (AMD) exists. Because cognitive impairment (CI) is associated with AMD, we used data from the Women’s Health Initiative (WHI) to search for a zinc/genetics interaction. Objective: To study the interaction of chronic zinc supplementation with genetic variants in CFH and ARMS2 on the development of CI. Background:Zinc dietary supplements, CFH and ARMS2 genotypes, and serial mental status was analyzed in participants with available genetic data (n = 7,483). Cognition was assessed using the Modified Mini-Mental State Examination. The development of CI over 5 years was analyzed by genotype and zinc intake using a repeated measures logistic regression model. Results:Zinc supplementation of approximately 15 mg/day was associated with decreased development of CI in women with 1 or 2 CFH and no ARMS2 risk alleles (OR = 0.46: 1 CFH risk allele; 0.20: 2 CFH risk alleles; p = 0.002). Conclusion:Low-dose zinc (approximately 15 mg) is associated with reduced CI in women with 2 CFH and 0 ARMS2 AMD risk alleles. This interaction is opposite in direction to that observed in AMD, where patients with 2 CFH and 0 ARMS2 risk alleles had increased progression to neovascular AMD if treated with 80 mg/day of zinc. This may be due to a zinc dose-response or to a fundamental difference in the role of zinc in the progression of early CI versus advanced AMD.
