TY - JOUR
T1 - Reduced CYP2D6 activity is a negative risk factor for methamphetamine dependence
AU - Otani, Kyohei
AU - Ujike, Hiroshi
AU - Sakai, Ayumu
AU - Okahisa, Yuko
AU - Kotaka, Tatsuya
AU - Inada, Toshiya
AU - Harano, Mutsuo
AU - Komiyama, Tokutaro
AU - Hori, Toru
AU - Yamada, Mitsuhiko
AU - Sekine, Yoshimoto
AU - Iwata, Nakao
AU - Iyo, Masaomi
AU - Sora, Ichiro
AU - Ozaki, Norio
AU - Kuroda, Shigetoshi
N1 - Funding Information:
We are grateful to Dr. Yutaro Suzuki from Niigata University for technical advice on CYP2D6 genotyping. This work was partly supported by the Zikei Institute of Psychiatry (Okayama, Japan) and Grants-in-Aid from the Japanese Ministry of Health, Labor and Welfare.
PY - 2008/3/21
Y1 - 2008/3/21
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/40649086616
UR - https://www.scopus.com/pages/publications/40649086616#tab=citedBy
U2 - 10.1016/j.neulet.2008.01.033
DO - 10.1016/j.neulet.2008.01.033
M3 - Article
C2 - 18280655
AN - SCOPUS:40649086616
SN - 0304-3940
VL - 434
SP - 88
EP - 92
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 1
ER -