Gene for AMD has now been identified by researchers

Mar 13 2005

Age-related macular degeneration (AMD) is a debilitating eye disease affecting about 15 million people in the United States.

It destroys vision by attacking an area of the retina called the macula, it is common in people age 60 or older. The macula, the most sensitive region of the retina,is responsible for fine-detail vision, which is needed for reading, driving and playing sports,watching movies and television. Yellowish waste deposits (drusen), in the normal aging process, accumulate around the macula, but in individuals with AMD, the drusen are larger and more numerous, often killing cells necessary for the health of nearby retinal photoreceptor cells. As these cells die in and around the macula, central vision is lost. Peripheral vision is not affected by AMD.

A gene for AMD has now been identified by researchers at Yale School of Medicine, on a region of chromosome 1, opening up the possibility for targeted treatment for this widespread eye disease that causes blindness in millions of people.

The study, by the Department of Epidemiology and Public Health (EPH) at Yale School of Medicine, Science Express, Rockefeller University and the National Eye Institute, used an interdisciplinary approach to conclude that the gene for a substance known as complement factor H (CFH) on chromosome 1 is associated with AMD.

"This is the first study to identify a common variant of the specific gene being associated with AMD," said Josephine Hoh. Caucasian AMD patients are at least four times more likely to have one particular alteration in the CFH gene that produces a different form of the CFH protein compared to individuals without the disease, she said. AMD appears in two forms, the more common "dry" form and the less common "wet" form. The wet form can very quickly lead to blindness, while the dry form progresses more slowly. Both are associated with the same variant in the CFH gene. The team used new genetic analysis and microscopic imaging technologies to find the genetic variant of the AMD gene.The study is different from previous research in that many more genetic markers were used to find the specific gene and variation. Past research has involved collecting family data that pinpoints a region on chromosome 1, but fails to find the specific gene.

The DNA of unrelated patients with AMD was analysed and their genetic profile compared to that of AMD-free controls. They applied computation-intensive, statistical analyses to the DNA information and found the differences between the two groups. The gene association has been confirmed by at least three independent studies with results about to be published.

The study is also important because it highlights the value in new paradigms for whole genome analysis for chronic diseases, says Hoh, who believes that in order to find genes responsible for diseases, a totally different approach must be used, instead of an educated guess. Their findings support the use of this technique.

The study will be published online in the March 10 issue of Science Express. Other authors on the study are Caroline Zeiss, Susan T. Mayne, Michael B. Bracken, Colin Barnstable and Shrikant M. Mane of Yale; Robert J. Klein, Richard S. Sackler, M.D., Chad Haynes and Jurg Ott of Rockefeller University; and Alice K. Henning, John Paul San Giovanni, Emily Y. Chew, M.D., and Frederick L. Ferris, M.D. of the National Eye Institute.