Title | CFH and ARMS2 Polymorphisms Interact with Zinc Supplements in Cognitive Impairment in the Women's Health Initiative Hormone Trial. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Kustra, R, Awh, CC, Rojas-Fernandez, C, Zanke, B |
Journal | J Alzheimers Dis |
Volume | 66 |
Issue | 2 |
Pagination | 707-715 |
Date Published | 2018 |
ISSN | 1875-8908 |
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. |
DOI | 10.3233/JAD-180673 |
Alternate Journal | J. Alzheimers Dis. |
PubMed ID | 30320589 |