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.
authors.affiliation: Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikata-cho 2-5-1, Okayama 700-8558, Japan.
authors.forename: Kyohei
authors.initials: K
authors.lastname: Otani
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ujike
authors.forename: Ayumu
authors.initials: A
authors.lastname: Sakai
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okahisa
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kotaka
authors.forename: Toshiya
authors.initials: T
authors.lastname: Inada
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Harano
authors.forename: Tokutaro
authors.initials: T
authors.lastname: Komiyama
authors.forename: Toru
authors.initials: T
authors.lastname: Hori
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Yamada
authors.forename: Yoshimoto
authors.initials: Y
authors.lastname: Sekine
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
authors.forename: Masaomi
authors.initials: M
authors.lastname: Iyo
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sora
authors.forename: Norio
authors.initials: N
authors.lastname: Ozaki
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Kuroda
mesh_terms: D000328:Adult; D019969:Amphetamine-Related Disorders / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology; D001921:Brain / Q000187:drug effects* / Q000201:enzymology* / Q000503:physiopathology; D001928:Brain Diseases, Metabolic / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D016022:Case-Control Studies; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000378:metabolism; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004252:DNA Mutational Analysis; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D007564:Japan / Q000208:ethnology; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects* / Q000378:metabolism; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D019389:Cytochrome P-450 CYP2D6