Otani Kyohei, Ujike Hiroshi, Sakai Ayumu, Okahisa Yuko, Kotaka Tatsuya, Inada Toshiya, Harano Mutsuo, Komiyama Tokutaro, Hori Toru, Yamada Mitsuhiko, Sekine Yoshimoto, Iwata Nakao, Iyo Masaomi, Sora Ichiro, Ozaki Norio, Kuroda Shigetoshi
Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikata-cho 2-5-1, Okayama 700-8558, Japan.
Neurosci Lett. 2008 Mar 21;434(1):88-92. doi: 10.1016/j.neulet.2008.01.033. Epub 2008 Jan 19.
Because methamphetamine (METH) is metabolized by CYP2D6 at the first step of hydroxylation and demethylation, it is possible that functional variants of CYP2D6 alter susceptibility to methamphetamine-induced dependence. We genotyped CYP2D6*1, *4, *5, *10, and *14 for 202 patients with METH dependence and 337 controls in a Japanese population and found a significant association of the CYP2D6 gene with METH dependence (p=0.0299). The patients had fewer *10 and *14 alleles, which are hypofunction alleles, than the controls. CYP2D6 genotypes were divided into three phenotypes: extensive metabolizers, intermediate metabolizers, and poor metabolizers. There was no poor metabolizer among our Japanese subjects, and intermediate metabolizers of CYP2D6 were significantly fewer in methamphetamine-dependent subjects than in controls (p=0.0212), with an odds ratio of 0.62 (95% confidence interval: 0.51-0.76). The present study demonstrated that reduced CYP2D6 activity was a negative risk factor for methamphetamine dependence.
由于甲基苯丙胺（METH）在羟基化和去甲基化的第一步由CYP2D6代谢，因此CYP2D6的功能变体可能会改变对甲基苯丙胺诱导的依赖的易感性。我们对202名日本甲基苯丙胺依赖患者和337名对照进行了CYP2D6*1、4、5、10和14基因分型，发现CYP2D6基因与甲基苯丙胺依赖存在显著关联（p=0.0299）。患者中功能低下的10和14等位基因比对照组少。CYP2D6基因型分为三种表型：快代谢型、中代谢型和慢代谢型。在我们的日本受试者中没有慢代谢型，甲基苯丙胺依赖受试者中CYP2D6中代谢型明显少于对照组（p=0.0212），优势比为0.62（95%置信区间：0.51-0.76）。本研究表明，CYP2D6活性降低是甲基苯丙胺依赖的一个负性危险因素。
