For people under 50, mutation may raise Parkinson’s risk

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A defect in a gene that produces dopamine in the brain appears to accelerate the onset of Parkinson’s disease. The effect is particularly dramatic for people under age 50.

Researchers found on average that Caucasians with one bad version of the gene—guanosine triphosphate cyclohydrolase-1 or GCH1—developed Parkinson’s symptoms five years earlier, and had a 23 percent increased risk for the disease.

However, young-to-middle-age adults with the mutation had a 45 percent increased risk of developing Parkinson’s disease. The presence of the defective gene in older adults had minimal effect.

Researchers know that rigidity and loss of muscle function associated with Parkinson’s is linked to a depletion of dopamine in the part of the brain that controls movement. For the current study scientists wanted to take a more holistic approach to better understand how the gene affects the course of the disease and certain outcomes such as motor skills and anxiety.

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Published in the journal Neurobiology of Aging, the study is the first to look at these different biological markers, as well has how the gene’s impact on dopamine production specifically affects Caucasian populations. Previous studies have focused primarily on Chinese and Taiwanese populations. The findings have the potential to help personalize medical care for people with a family history of Parkinson’s disease, similar to testing for the BRCA gene for women at risk for breast cancer.

“We want to have a more comprehensive understanding of what these genes related to Parkinson’s are doing at different points in someone’s lifetime,” says Auriel Willette, assistant professor of food science and human nutrition at Iowa State University. “Then, with genetic testing we can determine the risk for illness based on someone’s age, gender, weight, and other intervening factors.”

Data for the study were collected through the Parkinson’s Progression Markers Initiative, a public-private partnership sponsored by the Michael J. Fox Foundation for Parkinson’s Research. The initiative evaluates people with the disease to develop new and better treatments. The new study included 289 people recently diagnosed with Parkinson’s, but not on medication, and 233 healthy people.

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Researchers analyzed anxiety and motor function using the Unified Parkinson Disease Rating Scale—a tool that measures progression of the disease. They found those with the defective gene, regardless of age, were more anxious and struggled more with daily activities. However, the defective gene was not as strong of a predictor of developing Parkinson’s in people over 50.

“As we age, we progressively make less dopamine, and this effect strongly outweighs the genetic influences from the ‘bad version’ of this gene. Simply by aging, our dopamine production decreases to the point that the effects from a mutation in this gene are not noticeable in older adults, but make a big difference in younger populations,” says Joseph Webb, a graduate research assistant.

It is also important to pay attention to blood cholesterol levels. Cholesterol is directly related to the ability to produce dopamine. High LDL, or what’s considered “bad” cholesterol, is an established risk factor of Parkinson’s. The study shows that carriers of the defective GCH1 gene had higher cholesterol than non-carriers, which was true regardless of age.

Source: Iowa State University