1998 From: Ohio State University
Gene-Toxin Link May Shed Light On Cause Of Parkinson's DiseaseCOLUMBUS, Ohio -- Researchers seeking a cause for dementia in patients with Parkinson's disease have discovered that the combination of a defective gene and exposure to pesticides may increase a person's risk for developing the dementia. A study found that a group of Parkinson's patients whohad a particular mutant gene, or allele, and who were exposedto pesticides in the past, were three times more likely to develop dementia than Parkinson's patients who lacked the two factors. About one out of every five Parkinson's patients develops dementia. "The gene alone, coupled with environmental exposure, turned out to be a potent risk factor for Parkinson's with dementia in a group of patients with the disease," said Jean Hubble, clinical associate professor of neurology at Ohio State University. According to the study, published in a recent issue of Neuroepidemiology, potential risks for developing Parkinson's disease with dementia (PD+D) include pesticide exposure and at least one defective copy of a gene called CYP 2D6 29B+. This gene activates a series of enzymes in the liver that metabolize and detoxify chemicals that get into the body. Parkinson's disease is a muscular disorder that causes a person to lose control of coordination. It also causes tremors, poor balance, slowness and stooped posture. These symptoms are more severe in people with PD+D. The researchers studied 43 patients with PD+D and 51 with Parkinson's disease but who did not have dementia. They analyzed three genes suspected of playing a role in predisposing a person to the disease. They also considered three other characteristics shown to be more common among Parkinson's patients with dementia: Having less than 12 years of formal education, the onset of symptoms after age 60 and greater motor impairment. The researchers also considered substantial pesticide exposure and family history of the disease. "There was a hint that chemical exposures might be important where dementia is concerned," Hubble said, noting that past research has shown pesticide exposure to be a risk factor for Parkinson's disease. Researchers paired the three suspect genes with each other and with pesticide exposure. Only the mutant CYP gene-pesticide exposure combination emerged as a significant risk factor for dementia in Parkinson's. In the 43 patients with PD+D, 12 percent had both the defective gene and a history of pesticide exposure while 2 percent of the same group had neither factor. The study defined exposure to pesticides as 20 or more days in any given year. Hubble said the 20-day exposure is based on typical use of chemicals in commercial farming. But it's unclear if pesticides are a direct cause of PD+D. "Pesticides may be perfectly safe for 90 percent of the U.S. population because most people can readily detoxify these chemicals," Hubble said. "Perhaps there's a small percentage of individuals who cannot handle or detoxify chemical compounds because of their mutant CYP allele or other genetic factors." She said the results of the study should be interpreted with caution. "Our study does not show that pesticide exposure is the cause of dementia in Parkinson's disease," Hubble said. "All we've shown is that these two factors together appear to raise the relative risk of developing dementia in Parkinson's disease." Hubble conducted the study with researchers from the University of Kansas Medical Center, the Barrow Neurological Institute in Phoenix and the Geriatric Research Education and Clinical Center in Seattle. The study was funded with grants from the National Institute on Aging and the Parkinson's Disease Research Fund at the Barrow Neurological Institute. Written by Holly Wagner, (614)292-8310; [email protected]
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