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CFH and ARMS2 genetic polymorphisms predict response to antioxidants and zinc in patients with age-related macular degeneration.
Ophthalmology 2013; 120(11):2317-23O

Abstract

OBJECTIVE

The Age-Related Eye Disease Study (AREDS) demonstrated that antioxidant and zinc supplementation decreases progression to advanced age-related macular degeneration (AMD) in patients with moderate to severe disease. We evaluated the interaction of genetics and type of nutritional supplement on progression from moderate to advanced AMD.

DESIGN

Genetic analysis of a randomized, prospective clinical trial.

PARTICIPANTS

White patients with AREDS category 3 AMD in 1 eye and AREDS categories 1 through 4 AMD in the fellow eye enrolled in the AREDS with available peripheral blood-derived DNA (995).

METHODS

Subjects were evaluated for known AMD genetic risk markers and treatment category. The progression rate to advanced AMD was analyzed by genotypes and AREDS treatment group using Cox regression.

MAIN OUTCOME MEASURES

The effect of inherited gene polymorphisms on treatment group-specific rate of progression to advanced AMD.

RESULTS

Over an average of 10.1 years, individuals with 1 or 2 complement factor H (CFH) risk alleles derived maximum benefit from antioxidants alone. In these patients, the addition of zinc negated the benefits of antioxidants. Treatment with zinc and antioxidants was associated with a risk ratio (RR) of 1.83 with 2 CFH risk alleles (P = 1.03E-02), compared with outcomes for patients without CFH risk alleles. Patients with age-related maculopathy sensitivity 2 (ARMS2) risk alleles derived maximum benefit from zinc-containing regimens, with a deleterious response to antioxidants in the presence of ARMS2 risk alleles. Treatment with antioxidants was associated with an RR of 2.58 for those with 1 ARMS2 risk allele and 3.96 for those with 2 ARMS2 risk alleles (P = 1.04E-6), compared with patients with no ARMS2 risk alleles. Individuals homozygous for CFH and ARMS2 risk alleles derived no benefit from any category of AREDS treatment.

CONCLUSIONS

Individuals with moderate AMD could benefit from pharmacogenomic selection of nutritional supplements. In this analysis, patients with no CFH risk alleles and with 1 or 2 ARMS2 risk alleles derived maximum benefit from zinc-only supplementation. Patients with one or two CFH risk alleles and no ARMS2 risk alleles derived maximum benefit from antioxidant-only supplementation; treatment with zinc was associated with increased progression to advanced AMD. These recommendations could lead to improved outcomes through genotype-directed therapy.

Authors+Show Affiliations

Tennessee Retina, PC, Nashville, Tennessee.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23972322

Citation

Awh, Carl C., et al. "CFH and ARMS2 Genetic Polymorphisms Predict Response to Antioxidants and Zinc in Patients With Age-related Macular Degeneration." Ophthalmology, vol. 120, no. 11, 2013, pp. 2317-23.
Awh CC, Lane AM, Hawken S, et al. CFH and ARMS2 genetic polymorphisms predict response to antioxidants and zinc in patients with age-related macular degeneration. Ophthalmology. 2013;120(11):2317-23.
Awh, C. C., Lane, A. M., Hawken, S., Zanke, B., & Kim, I. K. (2013). CFH and ARMS2 genetic polymorphisms predict response to antioxidants and zinc in patients with age-related macular degeneration. Ophthalmology, 120(11), pp. 2317-23. doi:10.1016/j.ophtha.2013.07.039.
Awh CC, et al. CFH and ARMS2 Genetic Polymorphisms Predict Response to Antioxidants and Zinc in Patients With Age-related Macular Degeneration. Ophthalmology. 2013;120(11):2317-23. PubMed PMID: 23972322.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CFH and ARMS2 genetic polymorphisms predict response to antioxidants and zinc in patients with age-related macular degeneration. AU - Awh,Carl C, AU - Lane,Anne-Marie, AU - Hawken,Steven, AU - Zanke,Brent, AU - Kim,Ivana K, Y1 - 2013/08/21/ PY - 2013/05/31/received PY - 2013/07/24/revised PY - 2013/07/24/accepted PY - 2013/8/27/entrez PY - 2013/8/27/pubmed PY - 2014/1/11/medline SP - 2317 EP - 23 JF - Ophthalmology JO - Ophthalmology VL - 120 IS - 11 N2 - OBJECTIVE: The Age-Related Eye Disease Study (AREDS) demonstrated that antioxidant and zinc supplementation decreases progression to advanced age-related macular degeneration (AMD) in patients with moderate to severe disease. We evaluated the interaction of genetics and type of nutritional supplement on progression from moderate to advanced AMD. DESIGN: Genetic analysis of a randomized, prospective clinical trial. PARTICIPANTS: White patients with AREDS category 3 AMD in 1 eye and AREDS categories 1 through 4 AMD in the fellow eye enrolled in the AREDS with available peripheral blood-derived DNA (995). METHODS: Subjects were evaluated for known AMD genetic risk markers and treatment category. The progression rate to advanced AMD was analyzed by genotypes and AREDS treatment group using Cox regression. MAIN OUTCOME MEASURES: The effect of inherited gene polymorphisms on treatment group-specific rate of progression to advanced AMD. RESULTS: Over an average of 10.1 years, individuals with 1 or 2 complement factor H (CFH) risk alleles derived maximum benefit from antioxidants alone. In these patients, the addition of zinc negated the benefits of antioxidants. Treatment with zinc and antioxidants was associated with a risk ratio (RR) of 1.83 with 2 CFH risk alleles (P = 1.03E-02), compared with outcomes for patients without CFH risk alleles. Patients with age-related maculopathy sensitivity 2 (ARMS2) risk alleles derived maximum benefit from zinc-containing regimens, with a deleterious response to antioxidants in the presence of ARMS2 risk alleles. Treatment with antioxidants was associated with an RR of 2.58 for those with 1 ARMS2 risk allele and 3.96 for those with 2 ARMS2 risk alleles (P = 1.04E-6), compared with patients with no ARMS2 risk alleles. Individuals homozygous for CFH and ARMS2 risk alleles derived no benefit from any category of AREDS treatment. CONCLUSIONS: Individuals with moderate AMD could benefit from pharmacogenomic selection of nutritional supplements. In this analysis, patients with no CFH risk alleles and with 1 or 2 ARMS2 risk alleles derived maximum benefit from zinc-only supplementation. Patients with one or two CFH risk alleles and no ARMS2 risk alleles derived maximum benefit from antioxidant-only supplementation; treatment with zinc was associated with increased progression to advanced AMD. These recommendations could lead to improved outcomes through genotype-directed therapy. SN - 1549-4713 UR - https://www.unboundmedicine.com/medline/citation/23972322/CFH_and_ARMS2_genetic_polymorphisms_predict_response_to_antioxidants_and_zinc_in_patients_with_age_related_macular_degeneration_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-6420(13)00679-9 DB - PRIME DP - Unbound Medicine ER -