Nakatome Masato, Miyaji Akitaka, Mochizuki Kaori, Kishi Yubo, Isobe Ichiro, Matoba Ryoji
Legal Medicine, Department of Social and Environmental Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Leg Med (Tokyo). 2009 Apr;11 Suppl 1:S468-70. doi: 10.1016/j.legalmed.2009.01.095. Epub 2009 Feb 28.
Glutathione S-transferase (GST) plays a major role in the detoxification of many compounds by conjugation with glutathione. GSTM1 and T1, which are important members of the GST multigene family, are polymorphic in humans. Complete deletion of the gene results in the null genotype and loss of function. However, it is not clear whether deletion of this gene is associated with a vulnerability to methamphetamine (MAP) abuse. To clarify the potential role and mechanisms of genetic polymorphisms of GSTM1 and T1 in susceptibility to MAP abuse in the Japanese population, we investigated GSTM1 and T1 polymorphisms in subjects with diagnosed MAP-related disorders and in control groups. The risk of MAP abuse associated with GSTM1 null genotype was significantly higher only in females than in subjects with the GSTM1 genotype. GSTM1 and GSTT1 null genotype combined conferred increased risk for MAP abuse compared with GSTM1 and GSTT1 genotype combined. In conclusion, we found that GSTM1 gene deletion may contribute to a vulnerability to MAP abuse in female subjects. Moreover, we identified an association between GSTM1 and GSTT1 null genotype combined and risk of MAP abuse in the Japanese population.
谷胱甘肽S-转移酶（GST）通过与谷胱甘肽结合在许多化合物的解毒过程中起主要作用。GSTM1和T1是GST多基因家族的重要成员，在人类中具有多态性。基因的完全缺失会导致无效基因型和功能丧失。然而，该基因的缺失是否与甲基苯丙胺（MAP）滥用易感性相关尚不清楚。为了阐明GSTM1和T1基因多态性在日本人群对MAP滥用易感性中的潜在作用和机制，我们调查了诊断为MAP相关疾病的受试者和对照组中的GSTM1和T1多态性。与GSTM1基因型受试者相比，仅女性中与GSTM1无效基因型相关的MAP滥用风险显著更高。与GSTM1和GSTT1基因型组合相比，GSTM1和GSTT1无效基因型组合会增加MAP滥用风险。总之，我们发现GSTM1基因缺失可能导致女性受试者对MAP滥用的易感性。此外，我们确定了GSTM1和GSTT1无效基因型组合与日本人群中MAP滥用风险之间的关联。
