Genetic basis for Parkinson’s disease risk in pesticide-exposed individuals

The researchers emphasised the importance of understanding gene-environment interactions in elucidating PD pathogenesis and possibly developing strategies for prevention and treatment.
Genetic basis for Parkinson’s disease risk in pesticide-exposed individuals

VISAKHAPATNAM : A recent study conducted by scientists at the University of California, Los Angeles (UCLA) has shed further light on the relationship between pesticide exposure and Parkinson’s disease (PD) risk. Over decades, research has linked pesticide exposure to an increased risk of PD, prompting investigations into the underlying genetic factors that may contribute to this association.

Published in npj Parkinson’s Disease, the research analysed genetic data from a cohort of 757 PD patients enrolled in the Parkinson’s, Environment, and Genes (PEG) study. It focused on individuals with long-term exposure to pesticides commonly used on cotton crops, a population often subjected to repeated ambient pesticide exposure in agricultural regions of Central California. This pesticide cluster includes organophosphorus, organoarsenic, and n-methylcarbamate chemical classes.

Their analyses identified 36 variants in 26 genes that were enriched in PD patients with high pesticide exposure. Notably, the majority of these variants were found in genes associated with lysosomal function, which plays a crucial role in cellular waste disposal through a process called autophagy. Dysfunction of autophagy has also been implicated in Alzheimer’s disease.

The disruption of the lysosomal function can lead to the accumulation of toxic compounds, including alpha-synuclein, a protein implicated in PD pathology.

Of the 36 prioritised variants, 26 (72%) were linked to lysosomal function, suggesting a potential mechanism by which pesticide exposure may contribute to PD risk. Importantly, these variants were deemed deleterious to protein function, further supporting the hypothesis that impaired lysosomal activity may underlie the development of PD in individuals exposed to pesticides.

The study also highlighted the complex interplay between genetics and environmental factors in PD risk. While genetics alone accounts for a minority of PD cases, environmental exposures, such as pesticide exposure, can interact with genetic predispositions to increase disease risk.

The researchers emphasised the importance of understanding gene-environment interactions in elucidating PD pathogenesis and possibly developing strategies for prevention and treatment. The gene with the highest pesticide exposure and disease progression-associated variants identified in this study was EP300.

PD is the fastest-growing neurodegenerative disease worldwide. It is the second most common neurodegenerative disorder after Alzheimer’s. Understanding the genetic and environmental factors contributing to its development is crucial for improving prevention and treatment strategies.

The findings of this study build upon decades of research into the associations between pesticide exposure and PD risk. By identifying specific genetic variants associated with pesticide exposure and PD risk, the researchers have provided valuable insights into the underlying mechanisms of disease development.

Despite the study’s limitations, including the need for further investigation into the functional impact of identified variants, the researchers believe that continued research into gene-environment interactions could lead to novel strategies for PD prevention and treatment.

In all, 68 pesticides were studied for their links with PD. Several of the individual pesticides in the cluster have been previously linked to the disease. For example, trifluralin and phorate were associated with PD in an Agricultural Health Study, while aldicarb was linked to PD in a Dutch epidemiologic study. Other pesticides linked to autophagy and PD that could be of interest for future analysis, include chlorpyrifos, paraquat, and malathion, the researchers said.

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