Koizumi Hiroki, Hashimoto Kenji, Kumakiri Chikara, Shimizu Eiji, Sekine Yoshimoto, Ozaki Norio, Inada Toshiya, Harano Mutsuo, Komiyama Tokutaro, Yamada Mitsuhiko, Sora Ichiro, Ujike Hiroshi, Takei Nori, Iyo Masaomi
Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670, Japan.
Am J Med Genet B Neuropsychiatr Genet. 2004 Apr 1;126B(1):43-5. doi: 10.1002/ajmg.b.20148.
Several lines of evidence suggest that increased generation of auto-oxidized dopamine (DA) o-quinone is associated with the neurotoxicity of methamphetamine (MAP) in the brain, and that, as a cellular defenses against DA-derived quinines, glutathione S-transferase (GST) detoxifies auto-oxidized DA o-quinone in the brain. Glutathione S-transferase M1 (GSTM1) of the mu-class of GSTs catalyzes reaction between glutathione and catecholamine o-quinones under physiological conditions. This study was undertaken to investigate the role of the GSTM1 gene deletion polymorphism in the neuropathology of MAP abuse. One hundred fifty-seven MAP abusers and 200 healthy comparison subjects were tested for a genetic polymorphism of GSTM1. The difference in the frequency of deletion (D)/non-deletion (N) alleles between the female abusers and female controls was close to statistical significance (P = 0.071), although there was no statistical difference (P = 0.651) between male abusers and male controls. Furthermore, the number of female abusers with deletion alleles was significantly (P = 0.007, odds ratio: 2.77, 95% CI 1.30-5.89) higher than that of male abusers with deletion alleles. These findings suggest that GSTM1 gene deletion may contribute to a vulnerability to MAP abuse in female subjects, but not in male subjects.
多项证据表明，自氧化多巴胺（DA）邻醌生成增加与甲基苯丙胺（MAP）对大脑的神经毒性有关，并且作为针对DA衍生醌类的细胞防御机制，谷胱甘肽S-转移酶（GST）可使大脑中的自氧化DA邻醌解毒。GST的μ类谷胱甘肽S-转移酶M1（GSTM1）在生理条件下催化谷胱甘肽与儿茶酚胺邻醌之间的反应。本研究旨在探讨GSTM1基因缺失多态性在MAP滥用神经病理学中的作用。对157名MAP滥用者和200名健康对照者进行了GSTM1基因多态性检测。女性滥用者与女性对照者之间缺失（D）/非缺失（N）等位基因频率的差异接近统计学显著性（P = 0.071），尽管男性滥用者与男性对照者之间无统计学差异（P = 0.651）。此外，具有缺失等位基因的女性滥用者数量显著高于具有缺失等位基因的男性滥用者（P = 0.007，优势比：2.77，95%可信区间1.30 - 5.89）。这些发现表明，GSTM1基因缺失可能导致女性受试者易患MAP滥用，而男性受试者则不然。
