Evidence of a genetic risk factor for Parkinson’s disease

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A Mayo Clinic-led international research collaboration - one of the largest studies of its kind - provides strong evidence that a genetic risk factor may account for 3 percent of the cause of Parkinson’s disease.

Parkinson’s disease is a debilitating neurological disease that affects about 1 million people in the United States. Little is known about its causes and hence there is no cure.

“This is an important step forward because the contribution of common genetic risk factors to the development of Parkinson’s has long been suspected, but the high quality of data needed to make such discoveries has been missing,” says Demetrius Maraganore, M.D., Mayo Clinic neurologist and lead study investigator. “This well-designed and large study provides evidence that common genetic variants contribute to the cause of Parkinson’s.”

The collaboration included researchers from 11 countries. Their findings will be published in the Aug. 9 issue of the Journal of the American Medical Association. 

In their study, the researchers analyzed clinical and genetic data from 2,692 Parkinson’s disease patients and 2,652 healthy subjects who were matched to the Parkinson’s patients for age and gender. Results showed that persons with longer lengths of a DNA segment that promotes the activity of a gene known as alpha-synuclein had a 1.5 times greater risk for Parkinson’s disease.

Explains Dr. Maraganore, “Our study provides compelling evidence that variability in the alpha-synuclein gene is a risk factor for Parkinson’s disease worldwide. The common DNA variants that increase Parkinson’s disease risk cause the gene to produce too much alpha-synuclein protein in a process known as overexpression. Our findings support the development of therapies that reduce alpha-synuclein gene expression. Such therapies have the potential to prevent or delay the onset of Parkinson’s disease or to halt or slow its progression.”

Earlier, small studies showed that rare variations (mutations) in the alpha-synuclein gene caused Parkinson’s disease in a few isolated families. Further small studies suggested that common variations in the gene, while not sufficient to cause Parkinson’s, make people susceptible to the disease.

“However, the results of those small studies were inconsistent,” says Dr. Maraganore. “What was lacking was a well-designed, large study to see if common variations in the alpha-synuclein gene contribute to Parkinson’s risk worldwide. The current study provides this much-needed evidence. Alpha-synuclein gene variability was associated with Parkinson’s disease across several populations.”

http://www.mayo.edu

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