title: Rotenone, paraquat, and Parkinson's disease.
abstract: BACKGROUND
  Mitochondrial dysfunction and oxidative stress are pathophysiologic mechanisms implicated in experimental models and genetic forms of Parkinson's disease (PD). Certain pesticides may affect these mechanisms, but no pesticide has been definitively associated with PD in humans.
  
  
  OBJECTIVE
  Our goal was to determine whether pesticides that cause mitochondrial dysfunction or oxidative stress are associated with PD or clinical features of parkinsonism in humans.
  
  
  METHODS
  We assessed lifetime use of pesticides selected by mechanism in a case-control study nested in the Agricultural Health Study (AHS). PD was diagnosed by movement disorders specialists. Controls were a stratified random sample of all AHS participants frequency-matched to cases by age, sex, and state at approximately three controls:one case.
  
  
  RESULTS
  In 110 PD cases and 358 controls, PD was associated with use of a group of pesticides that inhibit mitochondrial complex I [odds ratio (OR)=1.7; 95% confidence interval (CI), 1.0-2.8] including rotenone (OR=2.5; 95% CI, 1.3-4.7) and with use of a group of pesticides that cause oxidative stress (OR = 2.0; 95% CI, 1.2-3.6), including paraquat (OR=2.5; 95% CI, 1.4-4.7).
  
  
  CONCLUSIONS
  PD was positively associated with two groups of pesticides defined by mechanisms implicated experimentally-those that impair mitochondrial function and those that increase oxidative stress-supporting a role for these mechanisms in PD pathophysiology.
authors.affiliation: The Parkinson's Institute, Sunnyvale, California 94085, USA. ctannermd@aol.com
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Tanner
authors.forename: Freya
authors.initials: F
authors.lastname: Kamel
authors.forename: G Webster
authors.initials: GW
authors.lastname: Ross
authors.forename: Jane A
authors.initials: JA
authors.lastname: Hoppin
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Goldman
authors.forename: Monica
authors.initials: M
authors.lastname: Korell
authors.forename: Connie
authors.initials: C
authors.lastname: Marras
authors.forename: Grace S
authors.initials: GS
authors.lastname: Bhudhikanok
authors.forename: Meike
authors.initials: M
authors.lastname: Kasten
authors.forename: Anabel R
authors.initials: AR
authors.lastname: Chade
authors.forename: Kathleen
authors.initials: K
authors.lastname: Comyns
authors.forename: Marie Barber
authors.initials: MB
authors.lastname: Richards
authors.forename: Cheryl
authors.initials: C
authors.lastname: Meng
authors.forename: Benjamin
authors.initials: B
authors.lastname: Priestley
authors.forename: Hubert H
authors.initials: HH
authors.lastname: Fernandez
authors.forename: Franca
authors.initials: F
authors.lastname: Cambi
authors.forename: David M
authors.initials: DM
authors.lastname: Umbach
authors.forename: Aaron
authors.initials: A
authors.lastname: Blair
authors.forename: Dale P
authors.initials: DP
authors.lastname: Sandler
authors.forename: J William
authors.initials: JW
authors.lastname: Langston
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D007484:Iowa / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D009657:North Carolina / Q000453:epidemiology; D016273:Occupational Exposure; D018384:Oxidative Stress; D010269:Paraquat / Q000633:toxicity*; D010300:Parkinson Disease / Q000453:epidemiology / Q000209:etiology*; D020734:Parkinsonian Disorders / Q000453:epidemiology / Q000209:etiology*; D012402:Rotenone / Q000633:toxicity*
chemical_list: D006540:Herbicides; D007306:Insecticides; D012402:Rotenone; D010269:Paraquat