Professional Exposure to Organophosphorus Insecticides, Paraoxonase (PON1) Polymorphisms, and Parkinson’s Disease (PD) among French Agricultural Workers

Abstract

ISEE-0620 Background: Professional pesticide exposure has been associated with PD. Paraoxonase (PON1) is involved in the metabolism of organophosphorus insecticides (OPs). PON1 has been studied in PD with conflicting results. PON1 expression and activity are modulated by 2 promoter (−161 C/T, −107 G/A) and 2 non-synonymous (Q192R, L55M) polymorphisms. We studied the relation between PD, OPs exposure, and PON1 polymorphisms in the setting of the Mutualité Sociale Agricole, the French social security for farm owners/helpers and other workers in the agricultural area. Methods: In the TERRE case-control study (1998–1999), 247 cases from 62 French districts with recently diagnosed PD were compared to 676 matched controls. Detailed pesticide data were collected by occupational physicians; questionnaires were reviewed by a panel of experts. DNA were collected and genotyped for the rs705381 (-161C/T), rs705379 (-107G/A), rs854560 (L55M), rs662 (R192Q) polymorphisms and an additional SNP (rs854565) that has been associated with Alzheimer’s disease. Analyses of pesticides were restricted to men (138 cases, 377 controls) who were considerably more frequently exposed than women. Results: There was no association between PD and any SNP overall. In men, the OR increased with the number of polymorphic L55M alleles (P = 0.03). PD was not associated with OPs overall (OR adjusted for age, gender, district, smoking = 1.3 [0.7–2.3]). Joint effect analyses in men effects yielded the following results: M-/OP-: OR = 1.0 (reference); M-/OP+: OR = 3.1 (1.1–9.2); M+/OP-: OR = 3.1 (1.3–7.8); M+/OP+: OR = 2.4 (0.9–6.3) (interaction OR = 0.4 [0.2–0.9], P = 0.03). Conclusion: We detected a complex pattern of interaction suggesting that (i) the L55M polymorphism was associated with PD among subjects not exposed to OPs, (ii) professional OPs exposure was associated with PD among subjects not carrying the L55M polymorphism and (iii) the association between PD and OPs disappeared among L55M carriers. These findings show that the relation between PD, PON1, and OPs is more complex than previously thought.