Menegon A, Board P G, Blackburn A C, Mellick G D, Le Couteur D G
Department of Pharmacology, University of Sydney, Canberra Clinical School, The Canberra Hospital, Australia.
Lancet. 1998 Oct 24;352(9137):1344-6. doi: 10.1016/s0140-6736(98)03453-9.
Parkinson's disease is thought to be secondary to the presence of neurotoxins, and pesticides have been implicated as possible causative agents. Glutathione transferases (GST) metabolise xenobiotics, including pesticides. Therefore, we investigated the role of GST polymorphisms in the pathogenesis of idiopathic Parkinson's disease.
We genotyped by PCR polymorphisms in four GST classes (GSTM1, GSTT1, GSTP1, and GSTZ1) in 95 Parkinson's disease patients and 95 controls. We asked all patients for information about pesticide exposure.
The distribution of the GSTP1 genotypes differed significantly between patients and controls who had been exposed to pesticides (controls vs patients: AA 14 [54%] of 26 vs seven [18%] of 39; AB 11 [42%] of 26 vs 22 [56%] of 39; BB 1 [4%] of 26 vs six [15%] of 39; AC 0 vs four [10%] of 39, p=0.009). No association was found with any of the other GST polymorphisms. Pesticide exposure and a positive family history were risk factors for Parkinson's disease.
GSTP1-1, which is expressed in the blood-brain barrier, may influence response to neurotoxins and explain the susceptibility of some people to the parkinsonism-inducing effects of pesticides.
帕金森病被认为继发于神经毒素的存在，农药被认为可能是致病因素。谷胱甘肽转移酶（GST）可代谢包括农药在内的外源性物质。因此，我们研究了GST基因多态性在特发性帕金森病发病机制中的作用。
我们采用聚合酶链反应（PCR）对95例帕金森病患者和95例对照者的4种GST类型（GSTM1、GSTT1、GSTP1和GSTZ1）的基因多态性进行基因分型。我们询问了所有患者有关农药暴露的信息。
在接触过农药的患者和对照者中，GSTP1基因型的分布存在显著差异（对照者与患者相比：AA，26例中的14例[54%]对39例中的7例[18%]；AB，26例中的11例[42%]对39例中的22例[56%]；BB，26例中的1例[4%]对39例中的6例[15%]；AC，0例对39例中的4例[10%]，p = 0.009）。未发现与其他任何GST基因多态性存在关联。农药暴露和阳性家族史是帕金森病的危险因素。
在血脑屏障中表达的GSTP1-1可能影响对神经毒素的反应，并解释了一些人对农药诱发帕金森综合征作用的易感性。
