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Study: Genetic analysis for AMD risk factors supports individualized benefits of supplements
Patients without CFH risk alleles derived maximum benefit from zinc, while those without ARMS2 risk alleles benefited from antioxidants.
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Patients with moderate age-related macular degeneration may benefit differentially from nutritional supplements in keeping with their genetic make-up, according to one study.
Genotype-directed therapy for patients who lack any complement factor H (CFH) risk alleles, but with one or two age-related maculopathy sensitivity 2 (ARMS2) alleles, reaped maximum benefit from zinc-only supplementation, according to co-author Brent W. Zanke, MD, PhD, chairman and chief medical officer of ArcticDx. Conversely, patients with one or two CFH risk alleles and no ARMS2 risk alleles derived maximum advantage from antioxidant-only supplementation, that is, vitamin C and vitamin D.
However, patients with two CFH risk alleles who were treated with zinc were about twice as likely to progress to advanced AMD compared with the average population, Zanke and colleagues said in a study published in Ophthalmology.
“Taking vitamins and minerals in very high concentrations is only moderately effective at preventing early-stage disease from progressing to late-stage disease,” Zanke said.
Brent W. Zanke
Gene-nutrient relationships
“We realized that some of the gene products (proteins and enzymes) that are important for causing AMD have a biochemical relationship with some of the minerals that are being used. The nutrients and gene products bind to one another, and they interact with and change the way they function,” Zanke told Ocular Surgery News. “For instance, it is accepted that zinc is a powerful inactivator of CFH, a gene important for AMD risk.”
Hence, Zanke and colleagues thought it would make sense to evaluate whether people with particular genetic make-ups respond differently to various nutritional supplements.
Of the 4,757 patients enrolled in the Age-Related Eye Disease Study, the authors selected for study only white patients with AREDS category 3 disease in at least one eye at the time of enrollment, totaling 2,258 patients. Of this subset, DNA was available for 995 patients. Patients were taking various kinds of nutritional supplements and followed on average for 10.1 years.
“We found that in some people, a particular kind of nutritional supplement was better than others, and in a small group of people, the currently recommended vitamin preparation actually makes their eyes worse,” Zanke said. “Therefore, people who are taking vitamins for their eyes should be genetically tested and determine what is the very best type of supplements for them.”
Individualized therapy
Zanke said that administration of zinc and antioxidants can be personalized by knowing what version of the two genes a patient possesses. For example, those with a “good form” (non-risk allele) of CFH respond well to zinc, while those with a “bad form” (risk allele) of CFH are made worse by zinc. Similarly, for ARMS2, those with the “good” version are made better with antioxidants and those with the “bad” version attain no benefit.
“For the first time, the huge investment that has been made in human genetics and eye studies is translated in a very simple way to benefit people,” Zanke said of the analysis. “We are proposing an evolution in practice. It is important for all of us to embrace research and manage our patients in the most modern and effective way possible. This is personalized medicine. … Physicians should study the data and conclusions carefully, so that they can manage their patients in the most responsible fashion.” – by Bob Kronemyer
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Emily Y. Chew, MD
Genetic testing may indeed result in a “personalized” approach to therapies for diseases such as breast cancer. The study by Awh et al has generated hypotheses regarding the potential of genetic testing to help determine the genetic influence on the outcome of progression to late AMD with each of the components of the Age-Related Eye Disease Study supplement, consisting of antioxidant vitamins and zinc. The report recommends administration of zinc or antioxidant vitamins alone, or the combination, depending on the analyses of genotypic subgroups with small sample sizes. However, AREDS required thousands of participants to demonstrate that the combination of antioxidant vitamins and zinc is beneficial, and neither vitamins nor zinc by itself was superior. This combination remains the treatment of choice.
Such hypotheses-generating data from this report are considered to be observational or retrospective and cannot be translated into treatment recommendations. These are subgroup analyses with insufficient power to achieve both statistical and clinical significance. Further validations of the statistical methodology used and the genetic markers considered in this study are needed. The American Academy of Ophthalmology Task Force recommends confining genetic testing for AMD to research studies.
The clinical use of pharmacogenetic information must be based upon strong evidence. In the case of genetic testing determining supplements for patients with AMD, the evidence falls far short of this goal.
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