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Variants in three estrogen-related genes linked to Parkinson's disease in women

April 05, 2006

ROCHESTER, Minn. - Mayo Clinic researchers have discovered a possible connection between increased risk for Parkinson's disease and variants in three genes that control estrogen production and activity in the body.

The findings will be presented Tuesday at the American Academy of Neurology meeting in San Diego.

"We and other investigators have found evidence that estrogen helps protect women from developing Parkinson's," says Walter Rocca, M.D., M.P.H., Mayo Clinic neurologist and epidemiologist, and lead study investigator. "So, a gene variant that would decrease estrogen production or activity would put those women at greater risk for the disease."

The study associated variants in the following three genes with development of Parkinson's: estrogen receptor 1 gene (ESR1); estrogen receptor 2 gene (ESR2); and PR domain-containing protein 2 gene (PRDM2).

"The gene variants are not a defect or a problem in and of themselves - they are part of human differences, simply differences across people, like being slim, short or blue-eyed," says Dr. Rocca. "These differences make one subgroup of the population more susceptible to a disease like Parkinson's. However, sometimes the genetic variant is a weak risk factor, and the disease only manifests if another risk factor is present, such as a particular diet, physical exercise, taking certain medications or a medical event."

The study was conducted using a database from a previous study of the entire human genome for genes linked to Parkinson's. For the new study, the Mayo Clinic investigators examined several genes for variants in 172 women who had Parkinson's and 229 women who did not have the disease.

Dr. Rocca explains that some genetic variants the study pinpointed for association with Parkinson's are quite common, affecting 10 to 20 percent of the female population. As women are not routinely tested for these gene variations, however, those affected would be unaware, he says.

"If the findings of this study are replicated and confirmed, the hope is to use these variants to predict the risk of disease using a simple blood test," says Dr. Rocca. He explains that the test would be particularly useful for women and their physicians before deciding to conduct an elective ovariectomy, surgical removal of the ovaries, because a combination of estrogen-reducing factors could amplify a woman's risk for Parkinson's.

Mayo Clinic