Reduced CYP2D6 activity is a negative risk factor for methamphetamine dependence.
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.
Otani
Kyohei
K
Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikata-cho 2-5-1, Okayama 700-8558, Japan.
Ujike
Hiroshi
H
Sakai
Ayumu
A
Okahisa
Yuko
Y
Kotaka
Tatsuya
T
Inada
Toshiya
T
Harano
Mutsuo
M
Komiyama
Tokutaro
T
Hori
Toru
T
Yamada
Mitsuhiko
M
Sekine
Yoshimoto
Y
Iwata
Nakao
N
Iyo
Masaomi
M
Sora
Ichiro
I
Ozaki
Norio
N
Kuroda
Shigetoshi
S
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
D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D019389:Cytochrome P-450 CYP2D6