Kishi Taro, Ikeda Masashi, Kitajima Tsuyoshi, Yamanouchi Yoshio, Kinoshita Yoko, Kawashima Kunihiro, Inada Toshiya, Harano Mutsuo, Komiyama Tokutaro, Hori Toru, Yamada Mitsuhiko, Iyo Masaomi, Sora Ichiro, Sekine Yoshimoto, Ozaki Norio, Ujike Hiroshi, Iwata Nakao
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan.
Ann N Y Acad Sci. 2008 Oct;1139:63-9. doi: 10.1196/annals.1432.022.
A recent study showed a significant association between schizophrenia in European samples and the glutamate cysteine ligase modifier (GCLM) subunit gene, which is the key glutathione (GSH)-synthesizing enzyme. Since the symptoms of methamphetamine (METH)-induced psychosis are similar to those of schizophrenia, the GCLM gene is thought to be a good candidate gene for METH-use disorder or related disorders. To evaluate the association between the GCLM gene and METH-use disorder and schizophrenia, we conducted a case-control study of Japanese subjects (METH-use disorder, 185 cases; schizophrenia, 742 cases; and controls, 819). Four SNPs (2 SNPs from an original report and JSNP database, and 2 "tagging SNPs" from HapMap database) in the GCLM gene were examined in this association analysis; one SNP showed an association with both METH-use disorder and METH-induced psychosis. After Bonferroni's correction for multiple testing, however, this significance disappeared. No significant association was found with schizophrenia. Our findings suggest that a common genetic variation in the GCLM gene might not contribute to the risk of METH-use disorder and schizophrenia in the Japanese population.
最近一项研究表明，在欧洲样本中，精神分裂症与谷氨酸半胱氨酸连接酶调节亚基（GCLM）基因之间存在显著关联，该基因是关键的谷胱甘肽（GSH）合成酶。由于甲基苯丙胺（METH）所致精神病的症状与精神分裂症相似，GCLM基因被认为是METH使用障碍或相关疾病的一个良好候选基因。为了评估GCLM基因与METH使用障碍及精神分裂症之间的关联，我们对日本受试者进行了一项病例对照研究（METH使用障碍，185例；精神分裂症，742例；对照，819例）。在该关联分析中检测了GCLM基因中的4个单核苷酸多态性（SNPs）（2个来自原始报告和JSNP数据库，2个来自HapMap数据库的“标签SNPs”）；其中一个SNP显示与METH使用障碍和METH所致精神病均有关联。然而，在进行Bonferroni多重检验校正后，这种显著性消失了。未发现与精神分裂症有显著关联。我们的研究结果表明，GCLM基因中的常见基因变异可能对日本人群中METH使用障碍和精神分裂症的风险没有影响。
