Human, animal and cell models support a role for pesticides in the etiology of Parkinson disease. Susceptibility to pesticides may be modified by genetic variants of xenobiotic enzymes, such as paraoxonase, that play a role in metabolizing some organophosphates.
We examined associations between Parkinson disease and the organophosphates diazinon, chlorpyrifos, and parathion, and the influence of a functional polymorphism at position 55 in the coding region of the PON1 gene (PON1-55). From 1 January 2001 through 1 January 2008, we recruited 351 incident cases and 363 controls from 3 rural California counties in a population-based case-control study. Participants provided a DNA sample, and residential exposure to organophosphates was determined from pesticide usage reports and a geographic information system (GIS) approach. We assessed the main effects of both genes and pesticides in unconditional logistic regression analyses, and evaluated the effect of carrying a PON1-55 MM variant on estimates of effects for diazinon, chlorpyrifos, and parathion exposures.
Carriers of the variant MM PON1-55 genotype exposed to organophosphates exhibited a greater than 2-fold increase in Parkinson disease risk compared with persons who had the wildtype or heterozygous genotype and no exposure (for diazinon, odds ratio = 2.2 [95% confidence interval = 1.1–4.5]; for chlorpyrifos, 2.6 [1.3–5.4]). The effect estimate for chlorpyrifos, was more pronounced in younger-onset cases and controls (≤60 years) (5.3 [1.7–16]). No increase in risk was noted for parathion.
The increase in risk we observed among PON1-55 variant carriers for specific organophosphates metabolized by PON1 underscores the importance of considering susceptibility factors when studying environmental exposures in Parkinson disease.
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From the aDepartment of Epidemiology, UCLA School of Public Health, Los Angeles, CA; bDepartment of Environmental Health Sciences, School of Public Health, UC Berkeley, CA; cDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA; dDepartment of Neurology, UCLA School of Medicine, Los Angeles, CA; and eDepartment of Environmental Health Sciences, Center for Occupational and Environmental Health (COEH), UCLA School of Public Health, Los Angeles, CA.
Submitted 22 November 2008; accepted 23 April 2009; posted 10 November 2009.
Supported by NIEHS# ES10544, NIEHS# U54ES12078 and NINDS#NS 038367, and DOD- PC051037 (Department of Defense Prostate Cancer Research Program); in addition, initial pilot funding was provided by the American Parkinson's Disease Association.
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Correspondence: Beate Ritz, Department of Epidemiology, UCLA, Box 951772, Los Angeles, CA 90095. E-mail: firstname.lastname@example.org.