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

被引：65

作者：

Benmoyal-Segal, L

Vander, T

Shifman, S

Bryk, B

Ebstein, R

Marcus, EL

Stessman, J

Darvasi, A

Herishanu, Y

Friedman, A

Soreq, H ^{[1
]}

机构：

[1] Hebrew Univ Jerusalem, Inst Life Sci, IL-91904 Jerusalem, Israel

[2] Ben Gurion Univ Negev, Zlotowsky Ctr Neurosci, Dept Neurol, IL-84105 Beer Sheva, Israel

[3] Ben Gurion Univ Negev, Zlotowsky Ctr Neurosci, Dept Neurosurg, IL-84105 Beer Sheva, Israel

[4] Soroka Med Ctr, IL-84101 Beer Sheva, Israel

[5] Herzog Hosp, Jerusalem, Israel

[6] Mt Scopus Hadassah Univ Hosp, Jerusalem, Israel

来源：

FASEB JOURNAL | 2005年 / 19卷 / 01期

关键词：

association study; environmental exposure; gene-environment interactions; genotyping neuroprotection;

D O I：

10.1096/fj.04-2106fje

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：452 / +

页数：17

共 43 条

[11] MAXIMUM LIKELIHOOD FROM INCOMPLETE DATA VIA EM ALGORITHM [J].