In a study published this month in Nature Genetics, Paul Bernstein, MD, PhD, of the Moran Eye Center and other researchers from Iceland, San Diego, Germany, and the Netherlands revealed the findings of a study, titled "A rare nonsynonymous sequence variant in C3 is associated with high risk of age-related macular degeneration."
Before the study, scientists already knew about a number of well-known major risk loci for AMD, but since it is a complex disease there are also rare variants that confer risk that are yet to be discovered, said Bernstein.
As part of the study, a group of Icelandic scientists studied whole genome sequencing on thousands of Icelandic AMD patients and controls and identified a previously unrecognized variant in the of the immune-related gene, complement factor 3 (C3). They found the mutation to be strongly associated with AMD risk. Whenever a new genetic association is found for a complex disease such as AMD, it is critical to replicate the findings in independent populations —which is where the Moran Eye Center came into the study, said Bernstein.
In Utah, 355 AMD patients and 163 age-matched controls were part of the United States’ replicate group that confirmed the original finding of the Icelandic scientists. Bernstein said although the C3 gene mutation is typically found in just 1 of 200 people, it is important because laboratory studies indicate that this particular variant would alter regulation of inflammation in tissues, a process that could have major impact on the progression of AMD. The discovery also confirms that targeting this pathway could be a useful area for drug development for AMD.
According to the American Academy of Ophthalmology, more than 2 million Americans age 50 and older have AMD. The condition results from deterioration the eye's macula. The macula is a small area in the retina — the light-sensitive tissue lining the back of the eye —which is the part of the retina responsible for central vision.
View the complete study