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Genetic Protection Against Parkinson’s
  
By
Edward R. Winstead


In an interesting twist on reports linking genes to the cause of disease, scientists report that a variant of a gene in mitochondria may actually protect people against Parkinson’s disease. Another, more common, form of the same gene may be a risk factor for the disease.

Furthermore, women in the study seemed to benefit more from the protective variant than did men. This is consistent with the fact that many more men than women are diagnosed with Parkinson’s, a progressive nerve disorder that initially impairs movement and is eventually fatal.

“The sex effect was surprising to me,” says Jeffery M. Vance of Duke University Medical Center in Durham, North Carolina, who led the study. “The variant that’s providing the protection seems to work more strongly in females than in males, and in fact that’s what we see in the clinic.”


‘Parkinson's is not one disease, but rather many diseases.’

Taking a genomic approach, the researchers analyzed nine DNA variants in the mitochondrial genomes of nearly a thousand individuals, including 600 Parkinson’s patients.

The researchers identified different variants of a mitochondrial gene called ND3 that are associated with a greater or lesser risk for developing Parkinson’s. One variant, called J, is much more common among people without the disease.

The variation occurs in the ND3 gene, which codes for part of a protein involved in generating energy. The researchers speculate that some forms of the protein, called complex I, make cells more efficient producers of energy.

For instance, the protective variant may increase energy production in the brain and other tissues. This variant may also be less susceptible to damage caused by cellular stress, which is thought to contribute to Parkinson’s.

Some Parkinson’s patients lack energy, and mitochondrial defects involving complex I have been implicated in the disease. But the evidence has come mainly from studies in animals and cell cultures. The new study, published in the American Journal of Human Genetics, provides DNA evidence.

“The genetic evidence really strengthens the argument that complex I is involved in Parkinson’s,” says Joelle M. van der Walt, a member of the Duke research team.

Though preliminary, the findings could eventually lead to a DNA test that identifies individuals at high risk in families with a history of Parkinson’s. Like other complex diseases, Parkinson’s probably involves many genetic and environmental factors, and identifying specific causes for the disease is more difficult when the study population is diverse. Using the new information, the Duke team will now try to group study subjects into more homogenous populations according to their mitochondrial DNA.

“Parkinson’s is not one disease, but rather many diseases,” says Vance. “Patients with similar symptoms may actually have distinct forms of the disease.” As more data accumulate about the genetic and environmental contributions to Parkinson's, individuals at risk may be able to take steps to prevent or delay onset of the disease.


Cartoon of mitochondrion.

The protective J variant is much more common among Hispanics and persons of African descent than Caucasians, and the prevalence of Parkinson’s is generally thought to be lower in these two groups than in Caucasians. The Duke study used subjects from an ongoing Parkinson’s study and most of the subjects happened to be of European descent.

Future studies will address the question of whether the frequency of the J variant in non-European populations contributes to the relatively low incidence of the disease.

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Van Der Walt, J.M. et al. Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease. Am J Hum Genet 72, 804-811 (April 2003).
 

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