CFH and LOC387715/ARMS2 Genotypes and Treatment with Antioxidants and Zinc for Age-Related Macular Degeneration
Received 19 October 2007; received in revised form 18 January 2008; accepted 18 January 2008. published online 17 April 2008.
Objective
To determine if CFH and LOC387715/ARMS2 genotypes influence treatment response to AREDS-type nutritional supplementation with antioxidants and zinc.
Design
Retrospective analysis of participants in a randomized, controlled clinical trial, the Age-Related Eye Disease Study (AREDS).
Participants and/or Controls
Eight hundred seventy-six AREDS study participants who were considered at high risk for developing advanced age-related macular degeneration (AMD).
Methods
Using DNA extracted from venous blood of 876 white participants in AREDS categories 3 and 4, that is, those considered to be at high risk for progression to advanced AMD, the authors genotyped for the single nucleotide polymorphisms in the CFH (Y402H, rs1061170) and LOC387715/ARMS2 (A69S, rs10490924) genes. The authors performed adjusted unconditional logistic regression analysis and assessed interactions of these genotypes to determine the relationship between CFH and LOC387715/ARMS2 genotype and treatment with antioxidants plus zinc.
Main Outcome Measures
Interaction between genetic variants and treatment response as determined by progression from high-risk to advanced AMD.
Results
Progression occurred in 264 of 876 patients from AREDS category 3 (intermediate AMD) to category 4 or 5 (unilateral or bilateral advanced AMD, respectively), or from category 4 to category 5. A treatment interaction was observed between the CFH Y402H genotype and supplementation with antioxidants plus zinc (CC; P = 0.03). An interaction (P = 0.004) was observed in the AREDS treatment groups taking zinc when compared with the groups taking no zinc, but not in groups taking antioxidants compared with those taking no antioxidants (P = 0.59). There were no significant treatment interactions observed with LOC387715/ARMS2.
Conclusions
The findings of this study indicate that an individual's response to AREDS supplements may be related to CFH genotype. This could have clinical relevance by predicting treatment outcome and potentially preventing unwanted side effects in those who may not benefit. Corroboration of these analyses is needed before considering modification of current management. This is among the first pharmacogenetic studies to suggest interaction between genotype and treatment.
Available online: April 17, 2008.
1Macular Degeneration Center, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon.
2Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts.
3Tufts-New England Medical Center, Ophthalmic Epidemiology and Genetics Service, Boston, Massachusetts.
4Laboratory of Statistical Genetics, Rockefeller University, New York, New York.
5Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
Correspondence to Michael L. Klein, MD, Casey Eye Institute, Oregon Health & Science University, 3375 SW Terwilliger Boulevard, Portland, OR 97239-4197.
Johanna M. Seddon, MD, ScM, Tufts-New England Medical Center, Ophthalmic Epidemiology and Genetics Service, 750 Washington Street, No. 450, Boston, MA 02111.
Manuscript no. 2007-1369.
Supported by the National Eye Institute, National Institutes of Health, Bethesda, Maryland (grant nos. R01-EY12203 [MLK] and R01-EY11309 [JMS]); China National Science Foundation, Beijing, China (grant no.: 30730057 [JO]); the Foundation Fighting Blindness, Owing Mills, Maryland (PJF, JMS, DWS); the Macular Vision Research Foundation, West Conshohocken, Pennsylvania (DWS); the Macular Degeneration Center Research Fund and the Goodall Macular Degeneration Fund, Casey Eye Institute, Portland, Oregon (MLK); Research to Prevent Blindness, Inc., New York, NY (unrestricted grants to the Casey Eye Institute and to Tufts-New England Eye Center and a Career Development Award to PJF); and the Macular Degeneration Research Fund, Tufts-New England Medical Center and Massachusetts Lions Eye Research Fund, Inc., Northboro, Massachusetts (JMS).
ABSTRACT