Reduced CYP2D6 activity is a negative risk factor for methamphetamine dependence

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 Sora, Norio Ozaki, Shigetoshi Kuroda

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)88-92
Number of pages5
JournalNeuroscience Letters
Volume434
Issue number1
DOIs
Publication statusPublished - 21-03-2008

Fingerprint

Cytochrome P-450 CYP2D6
Methamphetamine
Alleles
Hydroxylation
Odds Ratio
Genotype
Confidence Intervals
Phenotype
Population
Genes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Otani, K., Ujike, H., Sakai, A., Okahisa, Y., Kotaka, T., Inada, T., ... Kuroda, S. (2008). Reduced CYP2D6 activity is a negative risk factor for methamphetamine dependence. Neuroscience Letters, 434(1), 88-92. https://doi.org/10.1016/j.neulet.2008.01.033
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. / Reduced CYP2D6 activity is a negative risk factor for methamphetamine dependence. In: Neuroscience Letters. 2008 ; Vol. 434, No. 1. pp. 88-92.
@article{d2c68f87f32a478e90c84c4d4fb334a8,
title = "Reduced CYP2D6 activity is a negative risk factor for methamphetamine dependence",
abstract = "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.",
author = "Kyohei Otani and Hiroshi Ujike and Ayumu Sakai and Yuko Okahisa and Tatsuya Kotaka and Toshiya Inada and Mutsuo Harano and Tokutaro Komiyama and Toru Hori and Mitsuhiko Yamada and Yoshimoto Sekine and Nakao Iwata and Masaomi Iyo and Ichiro Sora and Norio Ozaki and Shigetoshi Kuroda",
year = "2008",
month = "3",
day = "21",
doi = "10.1016/j.neulet.2008.01.033",
language = "English",
volume = "434",
pages = "88--92",
journal = "Neuroscience Letters",
issn = "0304-3940",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

Otani, K, Ujike, H, Sakai, A, Okahisa, Y, Kotaka, T, Inada, T, Harano, M, Komiyama, T, Hori, T, Yamada, M, Sekine, Y, Iwata, N, Iyo, M, Sora, I, Ozaki, N & Kuroda, S 2008, 'Reduced CYP2D6 activity is a negative risk factor for methamphetamine dependence', Neuroscience Letters, vol. 434, no. 1, pp. 88-92. https://doi.org/10.1016/j.neulet.2008.01.033

Reduced CYP2D6 activity is a negative risk factor for methamphetamine dependence. / 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.

In: Neuroscience Letters, Vol. 434, No. 1, 21.03.2008, p. 88-92.

Research output: Contribution to journalArticle

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

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 - http://www.scopus.com/inward/record.url?scp=40649086616&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=40649086616&partnerID=8YFLogxK

U2 - 10.1016/j.neulet.2008.01.033

DO - 10.1016/j.neulet.2008.01.033

M3 - Article

C2 - 18280655

AN - SCOPUS:40649086616

VL - 434

SP - 88

EP - 92

JO - Neuroscience Letters

JF - Neuroscience Letters

SN - 0304-3940

IS - 1

ER -