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DURHAM, N.C. -- Inherited variations in proteins that produce energy for the body may provide protection from developing Parkinson's disease, according to a new study by scientists at Duke University Medical Center.

Furthermore, the inherited gene variations seem particularly to protect white women, which may help explain why Parkinson's disease is seen more often in men.

The study, published in the April 2003 issue of the American Journal of Human Genetics, is the first to assign specific genetic risk factors to the most common form of Parkinson's disease, which affects more than 1 million people in the United States.

The genetic risk factors for Parkinson's disease have been difficult to study because it is a complex disease that likely has both genetic and environmental components, said Jeffery Vance, M.D., lead author of the study. "We are finding that Parkinson's disease is not one disease; it is many diseases," he added.

The disease itself is a degenerative disorder of the portion of the brain that controls movement. Progressive nerve degeneration results in difficulty initiating movements such as walking, a loss of balance, rigidity and tremor.

Recent scientific studies had shown that people affected by Parkinson's disease have defects in mitochondria, the cellular components that produce energy for the body. Studies in rats have shown that chronic exposure to the common pesticide rotenone can cause damage to the energy producing proteins in the mitochondria and induce symptoms that mimic Parkinson's disease in people. These proteins, which together are called complex I, are among the few genes encoded in the genetic material of the mitochondria itself.

"Mitochondria have been implicated in Parkinson's disease, but no one really understood why," said Vance, an associate professor of medicine at Duke.

Vance and his colleagues decided to examine whether common gene variations called haplogroups that exist in the complex I proteins could change a person's susceptibility to developing Parkinson's disease.

The scientists examined the mitochondrial DNA of 609 Parkinson's disease patients and 340 normal controls who had no signs of the disease. In particular, they looked at nine well-known and well-studied gene variations that vary among ethnic groups. When they looked at the correlation between gene variation and incidence of Parkinson's disease, they discovered that one variant, called "J" was much more common in people who do not have Parkinson's disease, and particularly among women.

"The J haplogroup is much more common in unaffected individuals, so that would suggest it is protective," said Vance.

The J variant is found in about 26 percent of Caucasians, versus two-thirds of Asians and more than 90 percent of sub-Saharan Africans. However, the researchers noted that since they only studied Caucasians in this study, they could venture no conclusion about whether the J variant is protective in other ethnic groups.

"It is interesting, however, that this protective allele is more common in the groups that are thought to have a lower incidence of Parkinson disease," said Vance, adding that further research should help clarify the gene's protective effect.

The other gene variations studied showed no statistical variation among groups.

The scientists speculate that the J variant, which produces a protein differing by only one protein building block, turning the amino acid threonine into an alanine, may change its function slightly. The result, they say, could affect one's ability to process damaging oxygen free radicals that are a side effect of energy production. People carrying the J variant may be better prepared to handle oxidative stress than people carrying other variants.

"One of the mechanisms proposed to be responsible for degeneration of neurons involved in Parkinson's disease is excessive oxidative stress over time," said Vance. "The toxic effects resulting from excess oxygen damage, combined with exposure to pesticides such as rotenone, could act synergistically to cause Parkinson's disease. This is the first study to give substance to the idea."

Additional studies will be needed to further examine the link between variant J and Parkinson's disease, said Vance. Given the complex nature of the disease, the apparent protective effect of the J variant will need to be examined in other groups, and additional genetic and biochemical studies will be needed.

Joelle van der Walt, Kristin Nicodemis, Eden Martin, Ph.D., William Scott, Jeffrey Stajich, Adam McLaurin, Burton Scott, M.D., Donald Schmechel M.D., and Margaret Pericak-Vance, Ph.D., all of Duke, also contributed to the study, as did researchers from 14 additional medical centers across the United States.

The research was supported by a program project grant from the National Institutes of Health, and grants from the National Institute on Aging, the McKnight Foundation, GlaxoSmithKline, Inc. van der Walt is supported by a fellowship from the American Parkinson's Disease Foundation.