Paraoxonase 1, agricultural organophosphate exposure, and Parkinson disease

Epidemiology. 2010 Jan;21(1):87-94. doi: 10.1097/EDE.0b013e3181c15ec6.

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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Agriculture*
  • Aryldialkylphosphatase / genetics
  • Aryldialkylphosphatase / metabolism*
  • Base Sequence
  • California
  • Environmental Exposure / adverse effects*
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Odds Ratio
  • Organophosphates / adverse effects*
  • Parkinson Disease / etiology*
  • Polymorphism, Genetic
  • Risk Assessment

Substances

  • Organophosphates
  • Aryldialkylphosphatase
  • PON1 protein, human

Grant support