Brent Fogel, MD, PhD and Kimberly Carol Paul, PhD: Genetic variations may predispose people to Parkinson’s disease following long-term pesticide exposure, study finds

"A new UCLA Health study found certain genetic variants could help explain how long-term pesticide exposure may increase the risk of Parkinson’s disease.

While decades of research have linked pesticide exposure and Parkinson’s disease risk, researchers have sought to explain why some individuals with high exposure develop the disease while others do not.

One longstanding hypothesis has been that susceptibility to the disease is a combination of both environmental and genetic factors.

The new study(Link is external) (Link opens in new window), published in the journal NPJ Parkinson’s Disease, used genetic data from nearly 800 Central Valley (California) residents with Parkinson’s disease, many of whom had long-term exposure to 10 pesticides used on cotton crops for at least a decade prior to developing the disease, with some patients having been exposed as far back as 1974. They examined their genetic makeup for rare variants in genes associated with the function of lysosomes, cellular compartments that break down waste and debris, thought to be associated with the development of Parkinson’s disease, and looked for enrichment of variants in patients with high exposure to pesticide use compared to a representative sample of the general population.

Researchers found that variants in these genes were enriched in patients with more severe Parkinson’s disease who also had higher exposure to pesticides. These genetic variants also appeared to be deleterious to protein function suggesting that disruption of lysosomal activity may be underling the development of Parkinson’s disease combined with pesticide exposure.

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Dr. Brent Fogel(Link opens in new window), the study’s corresponding author and professor of Neurology and Human Genetics, said while the specific interactions between pesticides and the expression of these genetic variants requires further study, the results suggest that in someone with such variants, long-term exposure to the cotton pesticides could lead to the buildup of toxic compounds, due to alterations of the cells’ ability to break down damaged proteins and organelles -- a process known as autophagy – and thus lead to Parkinson’s disease.

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The study’s co-lead author and assistant professor of Neurology at UCLA, Dr. Kimberly Paul(Link is external) (Link opens in new window), said Parkinson’s disease is the fastest growing neurodegenerative disease in the world. While an increase in the number of new patients is expected given the large aging population in the U.S., the rate of new Parkinson’s disease patients is outpacing the rate that is expected from aging alone, Paul said."

Read more at UCLA Health.