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Genes Tied to Late-Onset Parkinson's

Mutations increase susceptibility to environmental factors

TUESDAY, Nov. 13, 2001 (HealthDayNews) -- Researchers say they now have convincing evidence that genetic flaws are involved in the most common form of Parkinson's disease that develops relatively late in life.

While specific genes previously have been linked to the relatively rare form of Parkinson's disease that strikes young people, the prevailing belief has been that the adult-onset form, which affects about 1 million Americans, is caused by as yet unidentified environmental factors.

Now researchers at Duke University Medical Center say a study of 174 families across the United States has established a link between several genes and a susceptibility to late-onset Parkinson's.

"What we have shown is that there is an underlying genetic susceptibility, but it's not that there is no environmental component. You have to have both," says lead study author Margaret A. Pericak-Vance, co-director of the Duke Center for Human Genetics. Findings appear in the Nov. 14 issue of the Journal of the American Medical Association.

The study links several genes, most notably a gene designated Parkin, which is known to be involved in both the early-onset form of Parkinson's and other Parkinson-related neurological disorders. Several other genes also are related to increased susceptibility to Parkinson's, the study finds.

Another report by Dr. Jeffrey Vance, Pericak-Vance's husband and co-director of the Duke Center for Human Genetics, says a gene designated "tau" is involved in Parkinson's. Though mutations of the tau gene have been linked to Alzheimer's disease and other conditions affecting mental function, this is the first time it has been linked to Parkinson's, Vance says.

The nature of that linkage and the role of the other genes identified in the studies still is not clear, he says. However, Vance says the important point is that "we have shown that genetics is important in Parkinson's disease. People have felt that it was much more an environmental disorder. It's going to end up being both. Some genes make people susceptible to different environmental factors, and not all the genes act in the same way."

The linkage differs from the genetics of other conditions, Vance says. "Now we are talking about susceptibility genes, not genes that actually cause the disease, like Tay-Sachs disease or Huntington's disease."

Almost nothing definite is known about the environmental risk factors that trigger Parkinson's, Vance says. There has been speculation but no specific proof about factors as diverse as cigarette smoking, pesticide exposure, head injuries and hormonal therapy for menopausal women.

"Now that we have identified the suspect genes, we can look for the environmental risk factors," says Pericak-Vance.

Vance says the findings open the possibility of preventive measures: "What it says is that there are ways of preventing it from happening. It is not a preordained thing."

What To Do: This is basic research that over years will enable follow-up studies of ways to attack and prevent Parkinson's disease. For comprehensive information about Parkinson's, consult the National Institute of Neurological Disorders and Stroke or the American Parkinson Disease Association.

SOURCES: Interviews with Margaret A. Pericak-Vance, Ph.D., and Jeffrey Vance, M.D., Ph.D., co-directors, Duke University Center for Human Genetics, Durham, N.C.; Nov. 14, 2001, Journal of the American Medical Association
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