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.
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: email@example.com.