Association study between polymorphisms in glutathione-related genes and methamphetamine use disorder in a Japanese population

Tasuku Hashimoto, Kenji Hashimoto, Ryosuke Miyatake, Daisuke Matsuzawa, Yoshimoto Sekine, Toshiya Inada, Norio Ozaki, Nakao Iwata, Mutsuo Harano, Tokutaro Komiyama, Mitsuhiko Yamada, Ichiro Sora, Hiroshi Ujike, Masaomi Iyo

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Abstract

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.

Original languageEnglish
Pages (from-to)1040-1046
Number of pages7
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume147
Issue number7
DOIs
Publication statusPublished - 05-10-2008

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All Science Journal Classification (ASJC) codes

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Hashimoto, T., Hashimoto, K., Miyatake, R., Matsuzawa, D., Sekine, Y., Inada, T., Ozaki, N., Iwata, N., Harano, M., Komiyama, T., Yamada, M., Sora, I., Ujike, H., & Iyo, M. (2008). Association study between polymorphisms in glutathione-related genes and methamphetamine use disorder in a Japanese population. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 147(7), 1040-1046. https://doi.org/10.1002/ajmg.b.30703