title: Paraoxonase 1, agricultural organophosphate exposure, and Parkinson disease.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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 (<or=60 years) (5.3 [1.7-16]). No increase in risk was noted for parathion.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Epidemiology, UCLA School of Public Health, Los Angeles, CA 90095, USA.
authors.forename: Angelika D
authors.initials: AD
authors.lastname: Manthripragada
authors.forename: Sadie
authors.initials: S
authors.lastname: Costello
authors.forename: Myles G
authors.initials: MG
authors.lastname: Cockburn
authors.forename: Jeff M
authors.initials: JM
authors.lastname: Bronstein
authors.forename: Beate
authors.initials: B
authors.lastname: Ritz
mesh_terms: D000383:Agriculture; D043303:Aryldialkylphosphatase / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002140:California; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010755:Organophosphates / Q000009:adverse effects*; D010300:Parkinson Disease / Q000209:etiology*; D011110:Polymorphism, Genetic; D018570:Risk Assessment
chemical_list: D010755:Organophosphates; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human