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Response to AREDS supplements according to genetic factors: survival analysis approach using the eye as the unit of analysis
- Source :
- British Journal of Ophthalmology. 100:1731-1737
- Publication Year :
- 2016
- Publisher :
- BMJ, 2016.
-
Abstract
- Background/aims The Age-Related Eye Disease Study (AREDS) reported the beneficial impact of antioxidant and zinc supplements on the risk of progression to advanced stages of age-related macular degeneration (AMD). We evaluated the role of genetic variants in modifying the relationship between supplementation and progression to advanced AMD. Methods Among 4124 eyes (2317 subjects with a genetic specimen), 882 progressed from no AMD, early or intermediate AMD to overall advanced disease, including geographic atrophy (GA) and neovascular disease (NV) over the course of the clinical trial. Survival analysis using individual eyes as the unit of analysis was used to assess the effect of supplementation on AMD outcomes, with adjustment for demographic, environmental, ocular and genetic covariates. Interaction effects between supplement groups and individual complement factor H (CFH) Y402H and age-related maculopathy susceptibility 2 ( ARMS2 ) genotypes, and composite genetic risk groups combining the number of risk alleles for both loci, were evaluated for their association with progression. Results Among antioxidant and zinc supplement users compared with the placebo group, subjects with a non-risk genotype for CFH (TT) had a lower risk of progression to advanced AMD (HR: 0.55, 95% CI 0.32 to 0.95, p=0.033). No significant treatment effect was apparent among subjects who were homozygous for the CFH risk allele (CC). A protective effect was observed among high-risk ARMS2 (TT) carriers (HR: 0.52, 95% CI 0.33 to 0.82, p=0.005). Similar results were seen for the NV subtype but not GA. Conclusions The effectiveness of antioxidant and zinc supplementation appears to differ by genotype. Further study is needed to determine the biological basis for this interaction. Trial registration number NCT00594672, pre-results.
- Subjects :
- Male
0301 basic medicine
Oncology
medicine.medical_specialty
Pathology
Genotype
genetic structures
Eye disease
Lower risk
Polymorphism, Single Nucleotide
Article
Antioxidants
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Double-Blind Method
Risk Factors
Geographic Atrophy
Internal medicine
Epidemiology
medicine
Humans
Prospective Studies
Allele
Prospective cohort study
Alleles
Survival analysis
Aged
business.industry
Proteins
DNA
Middle Aged
Macular degeneration
medicine.disease
Survival Analysis
eye diseases
Sensory Systems
Ophthalmology
030104 developmental biology
Zinc Compounds
Complement Factor H
Dietary Supplements
Disease Progression
030221 ophthalmology & optometry
Female
sense organs
business
Follow-Up Studies
Subjects
Details
- ISSN :
- 14682079 and 00071161
- Volume :
- 100
- Database :
- OpenAIRE
- Journal :
- British Journal of Ophthalmology
- Accession number :
- edsair.doi.dedup.....d91d0e1c56fdb5eb9403579b38c32b9b
- Full Text :
- https://doi.org/10.1136/bjophthalmol-2016-308624