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An Investigation into Household and Occupational Pesticide Exposures with Genetic Variants as Risk Factors for Parkinson's Disease


Epidemiologic studies suggest that pesticides are risk factors for Parkinson's Disease (PD) but predominantly assessed pesticide exposure as a broad category and often did not examine exposure modifying factors such as personal protective equipment (PPE) use and variants in genes that encode proteins involved in pesticide metabolism and distribution in the body. Only a handful have investigated household pesticide exposures alone. This dissertation research examined the relation between PD and exposures to pesticides from multiple exposure sources, including household use, occupational use, and ambient pesticide exposures from drift in addition to genetic variation in PON1 and ABCB1.

We recruited 360 incident PD cases and 827 population controls between 2001 through 2011 from central California, collected data on demographics, covariates, residential and occupational address history, and exposures to chemicals by telephone, and participants provided either whole blood or saliva samples.

Frequent use of any household pesticide increased PD risk by 47%; frequent use of products containing organophosphorus pesticides (OPs) increased risk more strongly by 71%, and frequent organothiophosphate use almost doubled the risk of PD. The largest odds ratios were estimated for frequent OP users who were carriers of the 192QQ paraoxonase genetic variant related to slower detoxification of OPs.

Ever occupational pesticide use for > 10 years doubled the risk of PD compared to never occupational pesticide users. PD risk was also increased with occupational use of fungicides, herbicides, insecticides, carbamates, OPs, and organochlorine (OC) pesticides. Surprisingly, we found higher risks among those who reported using PPE, possibly because these workers felt compelled to use PPE when handling toxic pesticides.

We replicated a prior finding of ABCB1 polymorphisms at both rs1045642 and rs2032582 modifying PD risk from occupational OC exposures. We also newly found that PD risk from occupational OP exposures is modified by these polymorphisms. However, we did not detect multiplicative interactions.

Our results suggest that exposures to OPs, carbamates, and OCs increase PD risk, and the risk from commonly used pesticides, specifically OCs and OPs, may be increased more strongly in individuals who are genetically susceptible to neurotoxic effects of pesticides.

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