Genetic mutations and exposure to pesticides have both been identified as risk factors for the development of Parkinson’s disease. Genes are implicated in a minority of cases but shed light on the role of abnormal lysosomal activity resulting in the aggregation of alpha-synuclein, the main component of Lewy bodies. Researchers at the University of California, Los Angeles wanted to better understand how genetic mutations and exposure to pesticides may interact with each other in the development of Parkinson’s.
In a study published in NPJ Parkinson’s Disease last month, researchers extracted data from 757 patients with Parkinson’s from the Parkinson’s, Environment, and Genes (PEG) study. The PEG study followed a cohort of 2,000 individuals living in California’s Central Valley who had been exposed long-term to a cluster of pesticides used in growing cotton. The study population for the current analysis was reduced to 386 individuals for whom detailed pesticide exposure data were available.
The analysis focused on 85 genes associated with lysosomal function and/or risk of developing Parkinson’s disease and looked at whether these genes were “enriched,” or appeared more frequently than would be expected due to chance, because of exposure to pesticides.
Study participants were classified based on Parkinson’s disease progression and level of pesticide exposure. Researchers looked at the individuals with both higher levels of pesticide exposure and greater disease progression, which led to the identification of 36 enriched mutations across 26 genes, the majority of which (72%) are associated with lysosomal function. Researchers compared these results to another patient population that had not been exposed to pesticides and found that only 3% of the 36 mutations were enriched.
“On a day-to-day basis, these variants are not having much of an impact. But under the right stress, such as exposure to certain pesticides, they can fail and that could, over time, lead to the development of Parkinson’s disease,” said study author Dr. Brent Fogel. “Better understanding of the genetic and environmental influences leading to Parkinson’s disease can help understand who might be at the most risk for developing it…This takes us one step closer to being able to prevent Parkinson’s disease in the future.”
