Genetic inheritance plays a big role in age-related macular degeneration (AMD), the leading cause of vision loss in older adults, two new studies have shown.
"We took a very detailed look at a gene that had previously been identified as being involved in AMD," explained the lead researcher for one study, Goncalo Abecasis, an associate professor of biostatistics at the University of Michigan, Ann Arbor. "We found there were many variants of the gene that could increase the risk of AMD - some with very large effects," he added.
The reports were published in the September issue of Nature Genetics.
AMD is a degenerative disorder that affects the retina, gradually reducing vision. The risk of developing the condition increases with age and is influenced by environmental as well as genetic factors.
Earlier studies have found that a genetic variant of a protein called complement factor H (CFH) to be associated with increased risk of developing AMD. These new studies show that other variants of the CFH gene also play an important role in the risk of AMD.
The first study
In the first study, Abecasis' team examined gene variants associated with the CFH gene. They studied these variants in 726 people with AMD and in 268 people who didn't have the condition.
They found that variants linked to CFH gene - which do not change the protein itself - significantly contribute to the risk of AMD. They also showed that multiple variants taken together increases risk factors.
"What was unusual about the finding was that these variants didn't have an obvious impact on the protein," Abecasis said. This finding could give scientists a more accurate means of determining an individual's specific risk for AMD.
The discovery may also help lead to new treatments. "We would like to be able to target the gene to reduce the risk of developing AMD," Abecasis said. "There are also other genes involved in AMD which need to be examined just as this one was," he noted.
The second study
The second study was led by Mark Daly, an assistant professor of medicine at Massachusetts General Hospital. His team examined the genetic causes of AMD cases and found that a common variant of CFH influenced the risk for AMD. As with Abecasis' study, this variant appeared to have no relation to the CFH protein. The Boston group studied over 1 200 people with AMD and more than 900 people without the disease.
They also confirmed links between AMD susceptibility and variations in two other genes. Together, genetic variations in these three genes accounted for a large proportion of people's increased risk for AMD, the report found.
"We identified a new gene variant that is associated with AMD," Daly said. "And we have confirmed several other findings. There is now confirmation of three genes involved in AMD," he added.
Brothers and sisters of people with AMD have a 3- to 6-fold higher risk of developing AMD compared with the general population, experts say. Daly's group now estimates that variations in these three genes account for about half of that increased risk.
With this information, researchers can start to look at people to determine their personal risk for developing AMD, Daly said.
That might help in the future, if and when effective treatments arose. However, "At this point, if there were more substantial measures in treating AMD, this would be more valuable information," Daly said. "At present, there are not really compelling ways of preventing the onset of disease."
"The new findings could yield effective ways to prevent or treat AMD," Daly said. Two other experts agreed. "These studies confirm what has already been known, but give us a better view on the subject," said Rando Allikmets, the Acquavella associate professor in ophthalmology and director of the molecular genetics laboratory at Columbia University Medical Center in New York City.
"Targeting these genes might help treat AMD by suppressing inflammation in the eye," he said. Michael Dean, head of the human genetics section at the US National Cancer Institute, said "prevention will be key."
"Now that we can identify people at risk for AMD, we need to identify them when they are young and follow them over time to see when AMD starts occurring and to see if there is a way delay or prevent the disease," he said.
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