Acetylcholinesterase/paraoxonase interactions increase the risk of insecticide-induced Parkinson's disease.
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.
Benmoyal-Segal
Liat
L
The Life Sciences Institute, The Hebrew University of Jerusalem, Israel.
Vander
Tatiana
T
Shifman
Sagiv
S
Bryk
Boris
B
Ebstein
Richard P
RP
Marcus
Esther-Lee
EL
Stessman
Jochanan
J
Darvasi
Ariel
A
Herishanu
Yuval
Y
Friedman
Alon
A
Soreq
Hermona
H
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
D002800:Cholinesterase Inhibitors; D007306:Insecticides; D000110:Acetylcholinesterase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human