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Genetic Polymorphisms of CFH and ARMS2 Do Not Predict Response to Antioxidants and Zinc in Patients with Age-Related Macular Degeneration
Open accessAbstract
Purpose Considerable controversy has erupted in recent years regarding whether genotyping should be part of standard care for patients with age-related macular degeneration (AMD) who are being considered for treatment with antioxidants and zinc. We aimed to determine whether genotype predicts response to supplements in AMD.Design Three separate statistical teams reanalyzed data derived from the Age-Related Eye Disease Study (AREDS), receiving data prepared by the AREDS investigators and, separately, data from investigators reporting findings that support the use of genotyping.Participants The population of interest was AREDS participants with AMD worse than category 1 and genotyping data available. Data from the 2 groups overlap imperfectly with respect to measurements made: the largest common set involved 879 participants for whom the same CFH and ARMS2 single nucleotide polymorphisms were measured by both groups.Methods Each team took a separate but complementary approach. One team focused on data concordance between conflicting studies. A second team focused on replicating the key claim of an interaction between genotype and treatment. The third team took a blank slate approach in attempting to find baseline predictors of treatment response.Main outcome measures Progression to advanced AMD.Results We found errors in the data used to support the initial claim of genotype-treatment interaction. Although we found evidence that high-risk patients had more to gain from treatment, we were unable to replicate any genotype-treatment interactions after adjusting for multiple testing. We tested 1 genotype claim on an independent set of data, with negative results. Even if we assumed that interactions in fact did exist, we did not find evidence to support the claim that supplementation leads to a large increase in the risk of advanced AMD in some genotype subgroups.Conclusions Patients who meet criteria for supplements to prevent AMD progression should be offered zinc and antioxidants without consideration of genotype.
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Additional investigators independently reviewed the AREDS data and concluded that no significant genetic associations existed.
“Additional investigators independently reviewed the AREDS data and concluded that no significant genetic associations existed [66].”
From Genetics and Age-Related Macular Degeneration: A Practical Review for Clinicians. (2024) · cites this paper as [66]
The Introduction and Discussion describe three independent statistical groups reanalyzing AREDS data and finding no evidence that genotype should guide antioxidant and zinc treatment. But “no significant genetic associations” is too broad: the Introduction reports a prognostic relationship between CFH/ARMS2 genotype and AMD progression, while the Results say no genotype–treatment interaction remained significant after correction for multiple testing. The indexed passages provide section labels but no page numbers. (LLM, conf=0.87)
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Metadata
- Authors
- Assel, M. J., Li, F., Wang, Y., Allen, A. S., Baggerly, K. A., & Vickers, A. J.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Duke University (US)
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Vickers, Andrew J.
- Venue
- Ophthalmology
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 125
- Issue
- 3
- Pages
- 391-397
- ISSN
- 0161-6420 (ISSN-L)
- PMC
- PMC5820191
- OpenAlex
- W2763231046
- Cited by
- 48
- References
- 12
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 11 · 2020: 8 · 2019: 9 · 2018: 9
- FWCI
- 6.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Ophthalmology (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (P30CA008748)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
- Keywords
- age-related macular degeneration, CFH gene, genetic polymorphism, genotype × treatment interaction, antioxidant supplementation, zinc supplementation, AREDS, treatment response prediction, data concordance, replication
- MeSH terms
- Aged, Alleles, Antioxidants, DNA, Female, Genotype, Humans, Macular Degeneration, Male, Prognosis, Proteins, Zinc, Complement Factor H, Disease Progression, Dietary Supplements, Polymorphism, Single Nucleotide
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