Could effectiveness of AREDS formula differ by genotype?

05-Dec-2016 - Last updated on 05-Dec-2016 at 15:05 GMT

AMD is a leading cause of vision loss among in people over 50. Image © iStock / Photokanok

The potential benefits of the AREDS formulation of antioxidants and zinc may be linked to your genotype, says a new study from Tufts and Harvard.

The effectiveness of AREDS supplements to reduce the risk of progression of age-related macular degeneration (AMD) was linked to specific genotypes associated with the disease, according to data published in the British Journal Ophthalmology.

“It is apparent that genetic susceptibility modifies the risk of progression to advanced AMD, can possibly affect response to anti-VEGF [antivascular endothelial growth factor] treatment and dietary patterns and the effectiveness of combination antioxidant and zinc supplementation may also differ by genotype,” wrote the authors.

“In this era of personalised medicine, genetic factors may become relevant when selecting specific treatments.”

AREDS formulation

The study was led by Dr Joanna Seddon, who was the first to report a link between lutein and eye health (JAMA, Vol. 272, pp. 1413-1420). While lutein and zeaxanthin were included in the second Age-Related Eye Disease Study (AREDS2), the original AREDS formulation contained only vitamin C (500 mg), vitamin E (400 IU), beta-carotene (15 mg), and zinc (80 mg).

For the new study Dr Seddon and her co-workers analyzed data from the original AREDS study and focused on two single nucleotide polymorphisms (SNPs) associated with AMD: complement factor H (CFH) Y402H (rs1061170) and age-related maculopathy susceptibility 2 (ARMS2) (rs10490924).

AREDS supplementation in people with a CFH (TT) genotype was associated with a 45% lower risk of AMD progression, compared with placebo, whereas no effect of the supplement was observed in people with CFH (CC) genotype.

In people with the ARMS2 (TT) genotype, considered at higher risk of AMD, the results showed that the AREDS supplements offered protection against AMD progression (48% lower risk, compared with placebo).

Building the science

DNA © iStock HYWARDS — Risk factors for AMD include age, smoking, race, and genetics. According to the National Eye Institute, researchers have identified about 20 genes that can affect AMD risk.Image © iStock/HYWARDS

“We first reported the independent association of these two genetic variants with progression to advanced stages of AMD in 2007, demonstrating a seven times increase in risk among the combined homozygous risk genotypes,” wrote the authors. “An interaction was suggested between CFH Y402H and the combination AREDS treatment (TT genotype, proportion progressing = 11% combination treatment, 34% placebo; CC genotype, proportion progressing = 39% combination treatment, 44% placebo).”

“Our present study further evaluates this potential interaction and underscores the differential effect of the combination antioxidant and zinc supplement by CFH genotype. Subjects with the non-risk genotype had a significantly lower risk of progression after treatment, while those with one or two risk alleles did not benefit.

“Our results implicate a possible interaction with ARMS2, where a protective effect of the combined supplementation was observed among high-risk ARMS2 carriers,” they wrote. Other studies have reported that DHA and/or EPA omega-3s may also have a beneficial effect in people with this genotype, they added.

Dr Seddon and her co-authors called for additional studies to determine the biological mechanism(s) and the “implications for the comprehensive management of AMD”.

Source: British Journal Ophthalmology
2016, Volume 100:1731-1737 doi:10.1136/bjophthalmol-2016-308624
“Response to AREDS supplements according to genetic factors: survival analysis approach using the eye as the unit of analysis”
Authors: J.M. Seddon et al.