Santt O, Baranova H, Albuisson E, Bignon Y-J, Lucotte G
Center of Molecular Neurogenetics, Paris, France.
Eur J Neurol. 2004 Apr;11(4):247-51. doi: 10.1046/j.1468-1331.2003.00756.x.
The present study was conducted to examine the interaction between cytochrome p450 2D6: CYP2D6 (phase I) poor metabolizer (PM) and glutathione S-transferase M1: GSTM1 (phase II) null genotypes, among 103 unrelated French Parkinson's disease (PD) patients. Both genes are involved in the biotransformation process, and the main objective of that work is to assess synergic effect between CYP2D6 PM and GSTM1 null genotypes in PD patients. Patients with both GSTM1 null genotype and poor metabolizer CYP2D6 have shown a strong dependency of multiplicative interaction (9.50; P = 0.016); this have also been observed when combining GSTM1 null with CYP2D6*4 deficient alleles, but were at the limit of significance (2.18; P = 0.076). Such a combination of polymorphic peculiarities in studied metabolic genes might represent additional risk factor for development of sporadic PD.
本研究旨在检测103名无亲缘关系的法国帕金森病（PD）患者中细胞色素P450 2D6（CYP2D6，I相）慢代谢者（PM）与谷胱甘肽S-转移酶M1（GSTM1，II相）无效基因型之间的相互作用。这两个基因都参与生物转化过程，该研究的主要目的是评估PD患者中CYP2D6 PM和GSTM1无效基因型之间的协同效应。GSTM1无效基因型和CYP2D6慢代谢者同时存在的患者显示出强烈的相乘相互作用依赖性（9.50；P = 0.016）；当将GSTM1无效基因型与CYP2D6 *4缺陷等位基因组合时也观察到这种情况，但处于显著性边缘（2.18；P = 0.076）。所研究代谢基因中这种多态性特征的组合可能代表散发性PD发生的额外危险因素。
