Objective
To determine whether genotypes at 2 major loci associated with late age-related macular
degeneration (AMD),
complement factor H (
CFH) and
age-related maculopathy susceptibility 2 (
ARMS2), influence the relative benefits of Age-Related Eye Disease Study (AREDS) supplements.
Design
Unplanned retrospective evaluation of a prospective, randomized, placebo-controlled
clinical trial of vitamins and minerals for the treatment of AMD.
Subjects
AREDS participants (mean age, 69 years) who were at risk of developing late AMD and
who were randomized to the 4 arms of AREDS supplement treatment.
Methods
Analyses were performed using the Cox proportional hazards model to predict progression
to late AMD (neovascular or central geographic atrophy). Statistical models, adjusted
for age, gender, smoking status, and baseline AMD severity, were used to examine the
influence of genotypes on the response to therapy with 4 randomly assigned arms of
AREDS supplement components: placebo, antioxidants (vitamin C, vitamin E, β-carotene),
zinc, or a combination.
Main Outcome Measures
The influence of the genotype on the relative treatment response to the randomized
components of the AREDS supplement, measured as progression to late AMD.
Results
Of the 1237 genotyped AREDS participants of white ethnicity, late AMD developed in
385 (31.1%) during the mean follow-up of 6.6 years. As previously demonstrated,
CFH genotype (
P = 0.005),
ARMS2 (
P< 0.0001), and supplement were associated individually with progression to late AMD.
An interaction analysis found no evidence that the relative benefits of AREDS supplementation
varied by genotype. Analysis of (1)
CFH rs1061170 and rs1410996 combined with
ARMS2 rs10490924 with the 4 randomly assigned arms of AREDS supplement and (2) analysis
of the combination of
CFH rs412852 and rs3766405 with
ARMS2 c.372_815del443ins54 with the AREDS components resulted in no interaction (
P = 0.06 and
P = 0.45, respectively, before multiplicity adjustment).
Conclusions
The AREDS supplements reduced the rate of AMD progression across all genotype groups.
Furthermore, the genotypes at the
CFH and
ARMS2 loci did not statistically significantly alter the benefits of AREDS supplements.
Genetic testing remains a valuable research tool, but these analyses suggest it provides
no benefits in managing nutritional supplementation for patients at risk of late AMD.
Abbreviations and Acronyms:
AMD ( age-related macular degeneration), AREDS ( Age-Related Eye Disease Study), ARMS2 ( age-related maculopathy susceptibility 2), CFH ( complement factor H), df ( degree of freedom), SNP ( single nucleotide polymorphism)To read this article in full you will need to make a payment
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Article Info
Publication History
Published online: June 26, 2014
Accepted:
May 9,
2014
Received in revised form:
April 17,
2014
Received:
March 26,
2014
Footnotes
∗Supplemental material is available at www.aaojournal.org.
Financial Disclosure(s): The author(s) have made the following disclosure(s):
Albert O. Edwards: Patent royalties—University of Michigan, Ann Arbor, Michigan.
Anand Swaroop: Patent royalties—University of Michigan, Ann Arbor, Michigan.
Lars G. Fritsche: Patent royalties—University of Regensburg, Regensburg, Germany (for age-related macular degeneration testing).
Gonçalo R. Abecasis: Consultancy—Regeneron; Patent royalties—University of Michigan, Ann Arbor, Michigan.
Supported by the National Eye Institute/National Institutes of Health , (contract no.: HHS-NOI-EY-0-2127), Bethesda Maryland. The sponsor and funding organization participated in the design and conduct of the study; data collection, management, analysis, and interpretation; and the preparation, review, and approval of the manuscript. The NIH holds a royalty-bearing license issued to Bausch & Lomb for the Age-Related Eye Disease Study Supplement. The Age-Related Eye Disease Study was a clinical trial that was conducted before the required clinical trials registration.
Identification
Copyright
© 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
