AMD prediction models consider genetics, environmental factors

NEW YORK – More than 20 genetic variants that influence the risk of age-related macular degeneration have been identified, knowledge that, when combined with environmental considerations, will allow for personalized medicine, according to Johanna M. Seddon, MD, ScM. Seddon, a professor of ophthalmology at Tufts University School of medicine and director of the ophthalmic epidemiology service at New England Eye Center, spoke at the Ocular Nutrition Society meeting, held in conjunction with Vision Expo East.

“The function of the common variants is poorly understood, but the rare variants – such as CFH, C3 and CFI – can have large biological effects and reveal disease mechanisms,” Seddon said.

For example, patients with complement factor H (CFH) have a high risk of developing AMD, she said.

“It causes early onset of disease and a more severe disease phenotype … through various mechanisms in the complement pathway,” Seddon said.

“The rare variants CFI, C3 and C9 were also found to be associated with a high risk,” she added.

Genes are important, but a patient’s environment can also modify genetic susceptibility, Seddon said. A favorable genotype in combination with a favorable diet results in lower risk.

C-reactive proteins (CRP) are independently associated with risk for AMD, Seddon said.

“The presence of both, a high CRP and risk variants for CFH and ARMS2, have been found to confer the highest risk,” she said.

“A possible treatment interaction between CFHY402H genotype and the AREDS supplement has also been found,” Seddon said. “The response to the AREDS supplement may be related to the CFH genotype; the low-risk genotype had greater reduction in risk. And it may be related to zinc components.”

Gene-supplement associations have been reported recently, she said.

“Awh found that if you didn’t have risk alleles for CFH, zinc only was better in terms of progression; if you didn’t have ARMS2, antioxidants were better and zinc appeared to increase progression,” Seddon said.

“Chew discussed the counterpoint, stating that simultaneous testing of all four treatment groups would be necessary,” Seddon said. “She said the number of the individuals in the subgroups in the Awh study was small, and the differences were not significant.

“There’s still some difference of opinion of this interpretation of that data,” she added.

Seddon shared her opinion: “These are plausible associations that require additional research and replication. There have been some suggestions of gene-nutrition, gene-supplement interactions and associations; they are definitely plausible. There’s not enough hard data to say it’s definite.”

She concluded: “We are in the era of personalized medicine whether we are ready or not. We will be facing doing genetic testing and prediction modeling in the not-too-distant future.” – by Nancy Hemphill, ELS

Disclosure: Seddon has no relevant financial disclosures.