Skip to comments.3 Studies Link Variant Gene to Risk of Severe Vision Loss (age-related macular degeneration)
Posted on 03/11/2005 8:25:29 PM PST by neverdem
Scientists say they have identified a genetic variation that substantially raises the risk of age-related macular degeneration, the leading cause of severe vision loss in the elderly.
The finding, being reported independently by three separate research groups, sheds light on the cause of the disease and could provide clues to how to develop treatments or strategies to prevent the condition.
The genetic variation "explains a lot of the risk," said Dr. Albert O. Edwards, an ophthalmology researcher in Dallas who led of one of the studies. "There's a primary biological explanation for A.M.D. now. It gives you some obvious avenues to start targeting treatments."
The variation, a change of a single unit of DNA out of the three billion units that make up the human genetic blueprint, appears to be common in the study subjects. So the findings could apply to many people.
Having the variant gene raises the risk of macular degeneration twofold to sevenfold, with the greatest risk for people with two copies of the variant gene.
More than 10 million Americans are estimated to have macular degeneration, though not all have vision loss, and experts expect the number to grow as baby boomers age. It damages the macula, the central part of the retina, which is responsible for detailed straight-ahead vision. People with advanced disease retain some peripheral vision but can lose the ability to drive, read, watch television or recognize faces, becoming functionally blind.
Two drugs are available to treat the more serious form of the disease, called wet A.M.D. Although they slow vision loss, they do not generally restore eyesight. There are no drugs to treat the dry form, which in itself does not usually lead to severe vision loss but often precedes the wet form.
Statements that a gene is linked to a disease sometime turn out to be premature, with other scientists' being unable to replicate the findings. But scientists said the new macular finding seemed strong, in part because it was made independently by groups using somewhat different approaches. The finding also seems to fit with other evidence.
Scientists said the variant might account for 20 percent to 50 percent of the risk of macular degeneration, but was not an absolute determinant. Some people in the studies who had the variant did not have the disease. Others did not have the variant but still had the disease.
"There are other things interacting here to come up with an individual final risk, things we don't even know about," said Dr. Margaret A. Pericak-Vance, director of the Center for Human Genetics at Duke University and a study leader.
Some factors are genetic and others environmental, scientists said. Previous studies have shown, for instance, that smoking or being obese raises the risk of macular degeneration and that eating leafy green vegetables, certain vitamins and zinc can lower it.
Dr. Stephen P. Daiger, a professor in the human genetics center at the University of Texas Health Science Center in Houston, said his lone doubt about the findings was that because the studies looked at small numbers of white Americans it is not known whether the findings apply to other ethnic groups. Dr. Daiger wrote a comment about the studies for the journal Science, which is publishing all three studies.
The authors of the studies said the disease was more frequent among whites. Dr. Edwards's study was done by scientists at the University of Texas Southwestern Medical Center in Dallas, Boston University and Sequenom, a biotechnology company in San Diego. Dr. Edwards has since left the University of Texas to start the Institute for Retina Research at Presbyterian Hospital of Dallas.
The study led by Dr. Pericak-Vance was at Duke and Vanderbilt. The third was led by Dr. Josephine Hoh at Yale and included researchers from the National Eye Institute and the Rockefeller University. Some of the institutions have applied for patents.
The genetic finding adds strong confirmation to accumulating evidence that macular degeneration, much like atherosclerosis, is at least partly caused by inflammation.
"The whole idea that inflammatory processes are involved in human diseases has taken on a lot of steam in recent years," said Dr. Lincoln V. Johnson, co-director of the Center for the Study of Macular Degeneration at the University of California, Santa Barbara. Dr. Johnson was not involved in the three studies but has conducted research that links inflammation to the disease.
All three studies pinpointed a single change in a letter of the genetic code in a gene that contains the code for a protein involved in the complement system, part of the body's immune response to invading pathogens. The change in the DNA letter led to a change of a single amino acid in the protein, complement factor H. Complement factor H acts as a brake on the immune response and inflammation. The variant form of the protein may be a less effective brake.
Dr. Johnson said anti-inflammatory drugs, or those that specifically inhibit the complement system, might one day help treat or prevent the disease. But he and other scientists said it would take years of testing to see whether any such drug worked for macular degeneration.
Similarly, Dr. Pericak-Vance of Duke said she would not recommend that people seek tests for the genetic variant to gauge increased risk. "We don't know enough about how to interpret it or what it means or what you would do about it," she said.
Previous studies of people with macular degeneration had linked a region of Chromosome 1 with macular degeneration. The Texas-Boston and the Duke-Vanderbilt teams focused on that region. The Yale group scanned the whole human genome, looking at more than 100,000 sites where the genetic code varies by one letter.
In the Texas study, 31.4 percent of the people with the disease had two copies of the variant gene, and 21.5 percent had no copies. In the control group without the disease, 13.7 percent had two copies of the variant and 42.6 percent had no copies. The rest, nearly half of both groups, had one copy of the variant.
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hmmm interesting. A.M.D. runs in my family. In fact, I think I got a letter from someone asking for test subjects and family groups or something. I gave it to my mom, who probably ignored it. It would have been a good family to use: grandma had 12 siblings and 7 children, lots of grandchildren from there.....
A friends mother has this and she is nearly blind in both eyes.
It seems more common than most people think.
I don't see how. Why would knowing it to be genetic change anything as far as patient care goes?
My 80 year old mother and one of other sisters, out of six siblings has this disorder. Both have complained most of their lives of the sun always being too bright and needing to wear sun glasses even on semi cloudy days to cut the glare. I don't know if there is a correlation or not.
Interesting, interesting. Thanks for the ping / post.
Good question. In the short term, not much, but in the long term drugs can be developed to counter the gene by disabling it or its effects. Lots of that type work going on. Most of the problems are not is the gene but the proteins associated with them.
My mother went almost blind, I have it and so does my son. The optomotist can see the early beginnings when she looks in my eyes but so far I don't think there's vision loss. I am very sensitive to light and my general vision continues to deteriorate... myopia, near sighted, astigmatism etc. oh well. may be the only way I get to retire. Sorry Judge, I can't read the pleadings.
There are some things currently used in alternative and integrative medicine that delay progression if done early enough.