Researchers have identified a genetic link that may increase the risk of developing Age-Related Macular Degeneration (AMD).1 An easy-to-use genetic test can identify two specific genes, complement factor H (CFH), and ARMS2/HTRA that have been linked with the disease.4
Original research from the Age-related Eye Disease Study (AREDS) investigated the role of a nutritional supplement containing antioxidants and zinc on AMD disease progression. Since 2001, the AREDS formulation has been widely recommended and considered to be beneficial to most people.2,3,4 An update in 2018 determined that zinc may actually be harmful to some people with a particular genetic profile.
What is age-related macular degeneration (AMD)?
Age-related macular degeneration is the primary cause of visual impairment and blindness in people older than age 50. There is no known treatment to prevent the early stages of macular degeneration, a condition that eventually affects the quality of central vision.3 AMD is expected to afflict nearly 20 million people in the US by 2020.2 As people continue to live longer, the incidence of age-related macular degeneration will increase worldwide.
Genetics and macular degeneration
Advances in genetic testing have led researchers to investigate the influence of supplements on disease progression, and prevention, of AMD in people with age-related macular degeneration.4
The Age-Related Eye Disease Study (AREDS) found that in people with moderate to severe disease, use of antioxidant and zinc supplements can slow progression to advanced stages of AMD. New data suggests some nutritional supplements interact with genetics to impact disease progression.5
Polymorphisms and supplements
The ongoing study evaluated specific subgroups and findings suggest that certain gene variations, called polymorphisms, are linked with the risk for advanced disease following treatment with antioxidant and zinc supplementation.3
Two genes and what do they do
The two genes most closely associated with AMD are known as complement factor H (CFH) and ARMS2/HTRA. They are alleles, mutations on a gene, that are found at the same position on a chromosome.
Complement Factor H gene (CFH)
CFH is a complement pathway regulator, responsible for a sequence of reactions, which play a role in the immune system. Under inflammatory conditions, it may cause the immune system to attack the retina. People with the CFH alleles benefited from treatment with antioxidants only.5
Important: Adding zinc canceled out benefits of antioxidants for those with the CFH gene, and in some people, it was associated with increased progression to advanced AMD.5
The way the ARMS2/HTRA gene works is not fully understood. Yet studies on patients with 1 or 2 ARMS2-risk alleles found treatment with zinc derived maximum benefit.5
A simple genetics swab test can offer doctors information necessary to determine if the AREDS formulation of supplements can be beneficial or damaging in treating AMD.2 An interaction between a person’s genetics and their prescribed treatment could produce an individualized reaction. This suggests that the treatment response to an AREDS formulation, known by many brand names, is largely determined by genetics.3
How much is the genetic test?
The only commercial genetics test currently available is made by the Canadian company ArcticDx. A cheek swab is all it takes to evaluate the underlying genetic profile that could indicate the appropriateness of specific supplements. The test, covered under some health insurance plans, costs around $500.2 It is important to talk to your doctor and health plan to find out if the test is appropriate for you, and whether its cost may be covered by your insurance.
Genetic testing results and nutritional supplements
The results of genetic testing can offer prescribers insight into pharmacological management, allowing them to select the optimal nutritional supplement for each patient with AMD.4 The updated study results indicate that an AREDS formulation could help about 35 percent of patients, and be harmful to nearly 13 percent of those with a particular genetic marker, quickening the loss of vision.2
Antioxidants, zinc, and AREDS
The risk of developing AMD is influenced by age, environment, and genetics. Physicians should consider the appropriateness of genetic testing to determine the right nutritional supplement for each AMD patient.3
AMD treatment with an AREDS formulation, a combination of high-dose antioxidants and zinc, can be helpful or harmful to patients based on their underlying genetics.4 The strong link could lead to improved outcomes based on genotype-directed therapy.5 Variations in genes can be predictors of disease progression.3 Those genetic factors can significantly affect the effectiveness and response to the AREDS supplements formulation.4
Dunaief, J. Should You Receive Genetic Testing for Age-Related Macular Degeneration? Available at: https://www.brightfocus.org/macular/article/should-you-receive-genetic-testing-for-age-related-macular-degeneration-amd. Accessed 4.17.19
Macular Degeneration Association Issues Urgent Supplement Warning for Patients. Available at: http://www.prweb.com/releases/2016/03/prweb13251076.htm. Accessed 4.15.19
Vavvas, D., Small,K., Awh, C. CFH and ARMS2 genetic risk determines progression to neovascular age-related macular degeneration after antioxidant and zinc supplementation. Available at: https://www.pnas.org/content/115/4/E696.short. Accessed 4.16.19
New study shows strong interaction between genetics and nutritional supplement treatment on progression to neovascular age-related macular degeneration (AMD) Available at:
http://macularisk.com/breaking-news.html. Accessed 4.16.19
Awh, C., Lane, A. et al. CFH and ARMS2 Genetic Polymorphisms Predict Response to Antioxidants and Zinc in Patients with Age-related Macular Degeneration. Available at:
https://www.aaojournal.org/article/S0161-6420(13)00679-9/abstract. Accessed 4.16.19.