title: Blood α-synuclein in agricultural pesticide handlers in central Washington State.
abstract: Epidemiologic studies suggest that occupational exposure to pesticides might increase Parkinson disease risk. Some pesticides, such as the organophosphorus insecticide chlorpyrifos, appear to increase the expression of α-synuclein, a protein critically involved in Parkinson disease. Therefore, we assessed total blood cell α-synuclein in 90 specimens from 63 agricultural pesticide handlers, mainly Hispanic men from central Washington State, who participated in the state's cholinesterase monitoring program in 2007-2010. Additionally, in age-adjusted linear regression models for repeated measures, we assessed whether α-synuclein levels were associated with butyrylcholinesterase-chlorpyrifos adducts or cholinesterase inhibition measured in peripheral blood, or with self-reported pesticide exposure or paraoxonase (PON1) genotype. There was no evidence by any of those indicators that exposure to chlorpyrifos was associated with greater blood α-synuclein. We observed somewhat greater α-synuclein with the PON1-108T (lower paraoxonase enzyme) allele, and with ≥ 10 h of exposure to cholinesterase inhibiting insecticides in the preceding 30 days, but neither of these associations followed a clear dose-response pattern. These results suggest that selected genetic and environmental factors may affect α-synuclein blood levels. However, longitudinal studies with larger numbers of pesticide handlers will be required to confirm and elucidate the possible associations observed in this exploratory cross-sectional study.
authors.affiliation: University of Washington, Department of Environmental and Occupational Health Sciences, Box 357234, Seattle, WA 98195, USA; University of Washington, Department of Neurology, Box 359775, Seattle, WA 98195-9775, USA. Electronic address: ssn@uw.edu.
authors.forename: Susan
authors.initials: S
authors.lastname: Searles Nielsen
authors.affiliation: University of California San Diego, Department of Family and Preventive Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA. Electronic address: hcheckoway@ucsd.edu.
authors.forename: Harvey
authors.initials: H
authors.lastname: Checkoway
authors.affiliation: University of Washington, Department of Pathology, Box 359635, Seattle, WA 98195, USA. Electronic address: zhangj@uw.edu.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: National Cancer Institute, Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, 9609 Medical Center Drive Bethesda, MD 20892, USA. Electronic address: hofmannjn@mail.nih.gov.
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Hofmann
authors.affiliation: National Farm Medicine Center, Marshfield Clinic Research Foundation, 1000 North Oak Avenue, Marshfield, WI 54449, USA. Electronic address: Keifer.matthew@mcrf.mfldclin.edu.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Keifer
authors.affiliation: University of Washington, Department of Environmental and Occupational Health Sciences, Box 357234, Seattle, WA 98195, USA. Electronic address: mpaulsen@uw.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Paulsen
authors.affiliation: University of Washington, Department of Environmental and Occupational Health Sciences, Box 357234, Seattle, WA 98195, USA. Electronic address: freddy@uw.edu.
authors.forename: Federico M
authors.initials: FM
authors.lastname: Farin
authors.affiliation: University of Washington, Department of Environmental and Occupational Health Sciences, Box 357234, Seattle, WA 98195, USA. Electronic address: ttjc@u.washington.edu.
authors.forename: Travis J
authors.initials: TJ
authors.lastname: Cook
authors.affiliation: University of Washington, Department of Environmental and Occupational Health Sciences, Box 357234, Seattle, WA 98195, USA. Electronic address: simpson1@uw.edu.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Simpson
mesh_terms: D000383:Agriculture; D006801:Humans; D008297:Male; D016273:Occupational Exposure; D010575:Pesticides / Q000633:toxicity*; D014861:Washington; D051844:alpha-Synuclein / Q000097:blood*
chemical_list: D010575:Pesticides; D051844:alpha-Synuclein
keywords: Aryldialkylphosphatase; Chlorpyrifos; Parkinson disease; Pesticides; α-Synuclein