title: Of Pesticides and Men: a California Story of Genes and Environment in Parkinson's Disease.
abstract: At the start of the postgenomics era, most Parkinson's disease (PD) etiology cannot be explained by our knowledge of genetic or environmental factors alone. For more than a decade, we have explored gene-environment (GxE) interactions possibly responsible for the heterogeneity of genetic as well as environmental results across populations. We developed three pesticide exposure measures (ambient due to agricultural applications, home and garden use, and occupational use) in a large population-based case-control study of incident PD in central California. Specifically, we assessed interactions with genes responsible for pesticide metabolism (PON1); transport across the blood-brain barrier (ABCB1); pesticides interfering with or depending on dopamine transporter activity (DAT/SLC6A3) and dopamine metabolism (ALDH2); impacting mitochondrial function via oxidative/nitrosative stress (NOS1) or proteasome inhibition (SKP1); and contributing to immune dysregulation (HLA-DR). These studies established some specificity for pesticides' neurodegenerative actions, contributed biologic plausibility to epidemiologic findings, and identified genetically susceptible populations.
authors: Department of Epidemiology, Fielding School of Public Health, UCLA, 650 Charles Young Dr South, Los Angeles, CA, 90095-1772, USA. britz@ucla.edu.|Center for Occupational and Environmental Health, UCLA, Los Angeles, CA, USA. britz@ucla.edu.|Department of Neurology, Geffen School of Medicine, UCLA, 710 Westwood Plaza, Los Angeles, CA, 90095, USA. britz@ucla.edu.
authors: Beate R
authors: BR
authors: Ritz
authors: Department of Epidemiology, Fielding School of Public Health, UCLA, 650 Charles Young Dr South, Los Angeles, CA, 90095-1772, USA.
authors: Kimberly C
authors: KC
authors: Paul
authors: Department of Neurology, Geffen School of Medicine, UCLA, 710 Westwood Plaza, Los Angeles, CA, 90095, USA.
authors: Jeff M
authors: JM
authors: Bronstein
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D000368:Aged; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D043303:Aryldialkylphosphatase; D002140:California / Q000453:epidemiology; D016022:Case-Control Studies; D050483:Dopamine Plasma Membrane Transport Proteins; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D059647:Gene-Environment Interaction; D006684:HLA-DR Antigens; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D052248:Nitric Oxide Synthase Type I; D010300:Parkinson Disease / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D010575:Pesticides / Q000633:toxicity*; D044786:S-Phase Kinase-Associated Proteins
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D050483:Dopamine Plasma Membrane Transport Proteins; D006684:HLA-DR Antigens; D010575:Pesticides; D044786:S-Phase Kinase-Associated Proteins; C097351:SKP1 protein, human; C493214:SLC6A3 protein, human; C496320:NOS1 protein, human; D052248:Nitric Oxide Synthase Type I; C096127:ALDH2 protein, human; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human
keywords: Gene–environment interactions; Parkinson’s disease; Pesticides