Format

Send to

Choose Destination
Ophthalmology. 2015 Jan;122(1):162-9. doi: 10.1016/j.ophtha.2014.07.049. Epub 2014 Sep 4.

Treatment response to antioxidants and zinc based on CFH and ARMS2 genetic risk allele number in the Age-Related Eye Disease Study.

Author information

1
Tennessee Retina, PC, Nashville, Tennessee. Electronic address: carlawh@gmail.com.
2
Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada.
3
Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada; Department of Epidemiology, Ottawa Hospital Research Institute and Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, Canada; The Arctic Group of Companies, Toronto, Canada.

Abstract

OBJECTIVE:

To evaluate the impact of complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) risk alleles on the observed response to components of the Age-Related Eye Disease Study (AREDS) formulation.

DESIGN:

Genetic and statistical subgroup analysis of a randomized, prospective clinical trial.

PARTICIPANTS:

White patients from the AREDS with category 3 or 4 age-related macular degeneration (AMD) with available DNA (n = 989).

METHODS:

Four genotype groups based on CFH and ARMS2 risk allele number were defined. Progression to advanced AMD was analyzed by genotype and treatment using Cox proportionate hazards estimates and 7-year events.

MAIN OUTCOME MEASURES:

The effect of predefined genotype group on treatment-specific progression to advanced AMD.

RESULTS:

Patients with 2 CFH risk alleles and no ARMS2 risk alleles progressed more with zinc-containing treatment compared with placebo, with a hazard ratio (HR) of 3.07 (P = 0.0196) for zinc and 2.73 (P = 0.0418) for AREDS formulation (AF). Seven-year treatment-specific progression rates were: placebo, 17.0%; zinc, 43.2% (P = 0.023); and AF, 40.2% (P = 0.039). Patients with 0 or 1 CFH risk alleles and 1 or 2 ARMS2 risk alleles benefited from zinc-containing treatment compared with placebo, with an HR of 0.514 for zinc (P = 0.012) and 0.569 for AF (P = 0.0254). Seven-year treatment-specific AMD progression rates were as follows: placebo, 43.3%; zinc, 25.2% (P = 0.020); and AF, 27.3% (P = 0.011). Zinc and AF treatment each interacted statistically with these 2 genotype groups under a Cox model, with P values of 0.000999 and 0.00366, respectively. For patients with 0 or 1 CFH risk alleles and no ARMS2 risk alleles, neither zinc-containing treatment altered progression compared with placebo, but treatment with antioxidants decreased progression (HR, 0.380; P = 0.034). Seven-year progression with placebo was 22.6% and with antioxidants was 9.17% (P = 0.033). For patients with 2 CFH risk alleles and 1 or 2 ARMS2 risk alleles, no treatment was better than placebo (48.4%).

CONCLUSIONS:

The benefit of the AREDS formulation seems the result of a favorable response by patients in only 1 genotype group, balanced by neutral or unfavorable responses in 3 genotype groups.

PMID:
25200399
DOI:
10.1016/j.ophtha.2014.07.049
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center