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No CFH or ARMS2 Interaction with Omega-3 Fatty Acids, Low versus High Zinc, or β-Carotene versus Lutein and Zeaxanthin on Progression of Age-Related Macular Degeneration in the Age-Related Eye Disease Study 2: Age-Related Eye Disease Study 2 Report No. 18.
Ophthalmology. 2019 11; 126(11):1541-1548.O

Abstract

PURPOSE

To assess whether genotypes at 2 major loci associated with age-related macular degeneration (AMD), complement factor H (CFH), or age-related maculopathy susceptibility 2 (ARMS2), modify the response to oral nutrients for the treatment of AMD in the Age-Related Eye Disease Study 2 (AREDS2).

DESIGN

Post hoc analysis of a randomized trial.

PARTICIPANTS

White AREDS2 participants.

METHODS

AREDS2 participants (n = 4203) with bilateral large drusen or late AMD in 1 eye were assigned randomly to lutein and zeaxanthin, omega-3 fatty acids, both, or placebo, and most also received the AREDS supplements. A secondary randomization assessed modified AREDS supplements in 4 treatment arms: lower zinc dosage, omission of β-carotene, both, or no modification. To evaluate the progression to late AMD, fundus photographs were obtained at baseline and annual study visits, and history of treatment for late AMD was obtained at study visits and 6-month interim telephone calls. Participants were genotyped for the single-nucleotide polymorphisms rs1061170 in CFH and rs10490924 in ARMS2. Bivariate frailty models using both eyes were conducted, including a gene-supplement interaction term and adjusting for age, gender, level of education, and smoking status. The main treatment effects, as well as the direct comparison between lutein plus zeaxanthin and β-carotene, were assessed for genotype interaction.

MAIN OUTCOME MEASURES

The interaction between genotype and the response to AREDS2 supplements regarding progression to late AMD, any geographic atrophy (GA), and neovascular AMD.

RESULTS

Complete data were available for 2775 eyes without baseline late AMD (1684 participants). The participants (mean age ± standard deviation, 72.1±7.7 years; 58.5% female) were followed up for a median of 5 years. The ARMS2 risk allele was associated significantly with progression to late AMD and neovascular AMD (P = 2.40 × 10-5 and P = 0.002, respectively), but not any GA (P = 0.097). The CFH risk allele was not associated with AMD progression. Genotype did not modify significantly the response to any of the AREDS2 supplements.

CONCLUSIONS

CFH and ARMS2 risk alleles do not modify the response to the AREDS2 nutrient supplements with respect to the progression to late AMD (GA and neovascular AMD).

Authors+Show Affiliations

Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, Maryland.Preventive Medicine and Genetics, Genomics & Informatics, University of Tennessee Health Science Center, Memphis, Tennessee.Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, Maryland.Biostatistics, The EMMES Company, Rockville, Maryland.Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, Maryland.Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, Maryland.Casey Eye Institute, Oregon Health and Science University, Portland, Oregon.Department of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC.Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, Maryland. Electronic address: echew@nei.nih.gov.No affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31358387

Citation

van Asten, Freekje, et al. "No CFH or ARMS2 Interaction With Omega-3 Fatty Acids, Low Versus High Zinc, or β-Carotene Versus Lutein and Zeaxanthin On Progression of Age-Related Macular Degeneration in the Age-Related Eye Disease Study 2: Age-Related Eye Disease Study 2 Report No. 18." Ophthalmology, vol. 126, no. 11, 2019, pp. 1541-1548.
van Asten F, Chiu CY, Agrón E, et al. No CFH or ARMS2 Interaction with Omega-3 Fatty Acids, Low versus High Zinc, or β-Carotene versus Lutein and Zeaxanthin on Progression of Age-Related Macular Degeneration in the Age-Related Eye Disease Study 2: Age-Related Eye Disease Study 2 Report No. 18. Ophthalmology. 2019;126(11):1541-1548.
van Asten, F., Chiu, C. Y., Agrón, E., Clemons, T. E., Ratnapriya, R., Swaroop, A., Klein, M. L., Fan, R., & Chew, E. Y. (2019). No CFH or ARMS2 Interaction with Omega-3 Fatty Acids, Low versus High Zinc, or β-Carotene versus Lutein and Zeaxanthin on Progression of Age-Related Macular Degeneration in the Age-Related Eye Disease Study 2: Age-Related Eye Disease Study 2 Report No. 18. Ophthalmology, 126(11), 1541-1548. https://doi.org/10.1016/j.ophtha.2019.06.004
van Asten F, et al. No CFH or ARMS2 Interaction With Omega-3 Fatty Acids, Low Versus High Zinc, or β-Carotene Versus Lutein and Zeaxanthin On Progression of Age-Related Macular Degeneration in the Age-Related Eye Disease Study 2: Age-Related Eye Disease Study 2 Report No. 18. Ophthalmology. 2019;126(11):1541-1548. PubMed PMID: 31358387.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - No CFH or ARMS2 Interaction with Omega-3 Fatty Acids, Low versus High Zinc, or β-Carotene versus Lutein and Zeaxanthin on Progression of Age-Related Macular Degeneration in the Age-Related Eye Disease Study 2: Age-Related Eye Disease Study 2 Report No. 18. AU - van Asten,Freekje, AU - Chiu,Chi-Yang, AU - Agrón,Elvira, AU - Clemons,Traci E, AU - Ratnapriya,Rinki, AU - Swaroop,Anand, AU - Klein,Michael L, AU - Fan,Ruzong, AU - Chew,Emily Y, AU - ,, Y1 - 2019/06/12/ PY - 2018/08/26/received PY - 2019/05/21/revised PY - 2019/06/04/accepted PY - 2019/7/31/pubmed PY - 2020/3/14/medline PY - 2019/7/31/entrez SP - 1541 EP - 1548 JF - Ophthalmology JO - Ophthalmology VL - 126 IS - 11 N2 - PURPOSE: To assess whether genotypes at 2 major loci associated with age-related macular degeneration (AMD), complement factor H (CFH), or age-related maculopathy susceptibility 2 (ARMS2), modify the response to oral nutrients for the treatment of AMD in the Age-Related Eye Disease Study 2 (AREDS2). DESIGN: Post hoc analysis of a randomized trial. PARTICIPANTS: White AREDS2 participants. METHODS: AREDS2 participants (n = 4203) with bilateral large drusen or late AMD in 1 eye were assigned randomly to lutein and zeaxanthin, omega-3 fatty acids, both, or placebo, and most also received the AREDS supplements. A secondary randomization assessed modified AREDS supplements in 4 treatment arms: lower zinc dosage, omission of β-carotene, both, or no modification. To evaluate the progression to late AMD, fundus photographs were obtained at baseline and annual study visits, and history of treatment for late AMD was obtained at study visits and 6-month interim telephone calls. Participants were genotyped for the single-nucleotide polymorphisms rs1061170 in CFH and rs10490924 in ARMS2. Bivariate frailty models using both eyes were conducted, including a gene-supplement interaction term and adjusting for age, gender, level of education, and smoking status. The main treatment effects, as well as the direct comparison between lutein plus zeaxanthin and β-carotene, were assessed for genotype interaction. MAIN OUTCOME MEASURES: The interaction between genotype and the response to AREDS2 supplements regarding progression to late AMD, any geographic atrophy (GA), and neovascular AMD. RESULTS: Complete data were available for 2775 eyes without baseline late AMD (1684 participants). The participants (mean age ± standard deviation, 72.1±7.7 years; 58.5% female) were followed up for a median of 5 years. The ARMS2 risk allele was associated significantly with progression to late AMD and neovascular AMD (P = 2.40 × 10-5 and P = 0.002, respectively), but not any GA (P = 0.097). The CFH risk allele was not associated with AMD progression. Genotype did not modify significantly the response to any of the AREDS2 supplements. CONCLUSIONS: CFH and ARMS2 risk alleles do not modify the response to the AREDS2 nutrient supplements with respect to the progression to late AMD (GA and neovascular AMD). SN - 1549-4713 UR - https://www.unboundmedicine.com/medline/citation/31358387/No_CFH_or_ARMS2_Interaction_with_Omega_3_Fatty_Acids_Low_versus_High_Zinc_or_β_Carotene_versus_Lutein_and_Zeaxanthin_on_Progression_of_Age_Related_Macular_Degeneration_in_the_Age_Related_Eye_Disease_Study_2:_Age_Related_Eye_Disease_Study_2_Report_No__18_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-6420(18)32155-9 DB - PRIME DP - Unbound Medicine ER -