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通过谷胱甘肽S-转移酶M1(GSTM1)和细胞色素P450 2D6(CYP2D6)酶系统的基因多态性研究多发性硬化症与有机溶剂暴露的关系。

Multiple sclerosis and exposure to organic solvents, investigated by genetic polymorphisms of the GSTM1 and CYP2D6 enzyme systems.

作者信息

Landtblom A M, Wastenson M, Ahmadi A, Söderkvist P

机构信息

Department of Neuroscience and Locomotion, Division of Neurology, Linköping University, S-581 85 Linköping, Sweden.

出版信息

Neurol Sci. 2003 Nov;24(4):248-51. doi: 10.1007/s10072-003-0148-5.

Abstract

An association between multiple sclerosis (MS) and exposure to organic solvents has been discussed. Organic solvents are metabolised by enzyme systems like glutathione Stransferase M1 (GSTM1) and CYP2D6, which express polymorphisms in the general population. GSTM1 null genotype has been associated with solvent-induced chronic toxic encephalopathy. Our aim was to see if a defect in one of these enzyme systems could explain the association between MS and exposure to organic solvents. In our study, 50 patients with MS were investigated, including 24 who had been significantly exposed to organic solvents and 26 who were not exposed. Polymerase chain reaction-based methods were used for genotyping GSTM1 and CYP2D6 polymorphisms in leukocyte DNA. No differences in genetic predisposition were found between MS patients exposed and those not exposed to organic solvents regarding GSTM1 null or CYP2D6 poor metaboliser genotypes. The possible association between multiple sclerosis and solvents may not, as for chronic toxic encephalopathy, be explained by defects in these systems.

摘要

多发性硬化症(MS)与接触有机溶剂之间的关联已被讨论。有机溶剂由谷胱甘肽S转移酶M1(GSTM1)和CYP2D6等酶系统代谢,这些酶系统在普通人群中存在多态性。GSTM1无效基因型与溶剂诱导的慢性中毒性脑病有关。我们的目的是研究这些酶系统之一的缺陷是否可以解释MS与接触有机溶剂之间的关联。在我们的研究中,对50例MS患者进行了调查,其中24例曾大量接触有机溶剂,26例未接触过。基于聚合酶链反应的方法用于对白细胞DNA中的GSTM1和CYP2D6多态性进行基因分型。在接触有机溶剂的MS患者和未接触有机溶剂的患者之间,就GSTM1无效或CYP2D6代谢不良基因型而言,未发现遗传易感性存在差异。多发性硬化症与溶剂之间可能的关联,不像慢性中毒性脑病那样,由这些系统的缺陷来解释。

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