title: Acetylcholinesterase/paraoxonase interactions increase the risk of insecticide-induced Parkinson's disease.
abstract: Exposure to agricultural insecticides, together with yet incompletely understood predisposing genotype/phenotype elements, notably increase the risk of Parkinson's disease. Here, we report findings attributing the increased risk in an insecticide-exposed rural area in Israel to interacting debilitating polymorphisms in the ACHE/PON1 locus and corresponding expression variations. Polymorphisms that debilitate PON1 activity and cause impaired AChE overproduction under anticholinesterase exposure were strongly overrepresented in patients from agriculturally exposed areas, indicating that they confer risk of Parkinson's disease. Supporting this notion, serum AChE and PON1 activities were both selectively and significantly lower in patients than in healthy individuals and in carriers of the risky polymorphisms as compared with other Parkinsonian patients. Our findings suggest that inherited interactive weakness of AChE and PON1 expression increases the insecticide-induced occurrence of Parkinson's disease.
authors.affiliation: The Life Sciences Institute, The Hebrew University of Jerusalem, Israel.
authors.forename: Liat
authors.initials: L
authors.lastname: Benmoyal-Segal
authors.forename: Tatiana
authors.initials: T
authors.lastname: Vander
authors.forename: Sagiv
authors.initials: S
authors.lastname: Shifman
authors.forename: Boris
authors.initials: B
authors.lastname: Bryk
authors.forename: Richard P
authors.initials: RP
authors.lastname: Ebstein
authors.forename: Esther-Lee
authors.initials: EL
authors.lastname: Marcus
authors.forename: Jochanan
authors.initials: J
authors.lastname: Stessman
authors.forename: Ariel
authors.initials: A
authors.lastname: Darvasi
authors.forename: Yuval
authors.initials: Y
authors.lastname: Herishanu
authors.forename: Alon
authors.initials: A
authors.lastname: Friedman
authors.forename: Hermona
authors.initials: H
authors.lastname: Soreq
mesh_terms: D000110:Acetylcholinesterase / Q000097:blood / Q000235:genetics*; D000328:Adult; D000368:Aged; D043303:Aryldialkylphosphatase / Q000097:blood / Q000235:genetics*; D002800:Cholinesterase Inhibitors / Q000009:adverse effects; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007306:Insecticides / Q000009:adverse effects*; D007557:Israel; D015810:Linkage Disequilibrium; D008875:Middle Aged; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000235:genetics; D011041:Poisoning; D011110:Polymorphism, Genetic; D012424:Rural Population
chemical_list: D002800:Cholinesterase Inhibitors; D007306:Insecticides; D000110:Acetylcholinesterase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human