Association study between polymorphisms in glutathione-related genes and methamphetamine use disorder in a Japanese population.
Accumulating evidence suggests that oxidative stress plays a role in the mechanisms of action of methamphetamine (METH) in the brain. In the present study, we investigated the association between the genetic polymorphisms among glutathione (GSH)-related enzymes; glutathione S-transferases (GSTs) such as GSTT1 (Non-deletion/Null), GSTT2 (Met139Ile), GSTA1 (-69C/T), and GSTO1 (Ala140Asp); glutathione peroxidase 1 (GPX1) (Pro198Leu); and glutamate-cysteine ligase modifier (GCLM) subunit and METH use disorder in a Japanese population. Two hundred eighteen METH abusers and 233 healthy controls were enrolled in the study. There was a significant difference in GSTT1 genotype frequency between patients with METH psychosis and controls (P = 0.039, odds ratio: 1.52, 95% CI 1.03-2.24). Furthermore, the frequency (66.0%) of the GSTT1 null genotype among prolonged-type METH psychotic patients with spontaneous relapse was significantly higher (P = 0.025, odds ratio: 2.43, 95% CI 1.13-5.23) than that (44.4%) of transient-type METH psychotic patients without spontaneous relapse. However, there were no associations between the polymorphisms of other genes and METH abuse. The present study suggests that the polymorphism of the GSTT1 gene might be a genetic risk factor of the development of METH psychosis in a Japanese population.
Hashimoto
Tasuku
T
Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan. hashimoto@faculty.chiba-u.jp
Hashimoto
Kenji
K
Miyatake
Ryosuke
R
Matsuzawa
Daisuke
D
Sekine
Yoshimoto
Y
Inada
Toshiya
T
Ozaki
Norio
N
Iwata
Nakao
N
Harano
Mutsuo
M
Komiyama
Tokutaro
T
Yamada
Mitsuhiko
M
Sora
Ichiro
I
Ujike
Hiroshi
H
Iyo
Masaomi
M
D000328:Adult; D000368:Aged; D019969:Amphetamine-Related Disorders / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008694:Methamphetamine; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012008:Recurrence
D008694:Methamphetamine; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase