Details

Autor(en) / Beteiligte

• Manthripragada, Angelika D.
• Costello, Sadie
• Cockburn, Myles G.
• Bronstein, Jeff M.
• Ritz, Beate

Titel

Paraoxonase 1, Agricultural Organophosphate Exposure, and Parkinson Disease

Ist Teil von

• Epidemiology (Cambridge, Mass.), 2010-01, Vol.21 (1), p.87-94

Ort / Verlag

Philadelphia, PA: Lippincott Williams & Wilkins

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 (≤60 years) (5.3 [1.7–1.6]). 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.