Acetylcholinesterase/paraoxonase interactions increase the risk of insecticide-induced Parkinson’s disease

SPECIFIC AIMSTo decipher gene/environment interactions that increase the risk of anticholinesterase exposure-induced Parkinson’s disease, we studied interacting polymorphisms in the ACHE/PON1 locus and corresponding expression variations in Israeli patients from agriculturally exposed areas. At a biochemical level, serum AChE and PON1 activities were compared between patients and healthy individuals and between risky polymorphism carriers to other parkinsonians.PRINCIPAL FINDINGS1. Apparent association with exposure-induced PD riskAllelic composition of the ACHE/PON1 locus from insecticide-exposed and nonexposed PD patients was similar to that of healthy individuals, allowing comparison between patients and controls despite age differences. Three polymorphisms showed a nonsignificant trend for association with exposure-induced PD: –162PON1, –108PON1, ΔACHE, P < 0.1. The –108PON1 SNP and ΔACHE reflect functionally effective changes, with their rare alleles impairing production of PON1 and insult-induced ov...