Reduced CYP2D6 activity is a negative risk factor for methamphetamine dependence
- 作者：Kyohei Otani ; Hiroshi Ujike ; Ayumu Sakai ; Yuko Okahisa ; Tatsuya Kotaka ; Toshiya Inada ; Mutsuo Harano ; Tokutaro Komiyama ; Toru Hori ; Mitsuhiko Yamada ; Yoshimoto Sekine ; Nakao Iwata ; Masaomi Iyo ; Ichiro
- 关键词：CYP2D6 ; Methamphetamine ; Amphetamine ; Dependence ; Intermediate metabolizer ; Case-control association study
- 刊名：Neuroscience Letters
- 出版年：2008
- 期刊代码：52_03043940
- 类别：neu
- 出版时间：21 March 2008
- 卷：434
- 期：1
- 页码：88-92
- 文件大小：110 K
摘要
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.