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Association between the glutathione S‐transferase M1 gene deletion and female methamphetamine abusers
Author(s) -
Koizumi Hiroki,
Hashimoto Kenji,
Kumakiri Chikara,
Shimizu Eiji,
Sekine Yoshimoto,
Ozaki Norio,
Inada Toshiya,
Harano Mutsuo,
Komiyama Tokutaro,
Yamada Mitsuhiko,
Sora Ichiro,
Ujike Hiroshi,
Takei Nori,
Iyo Masaomi
Publication year - 2003
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.20148
Subject(s) - glutathione s transferase , glutathione , allele , methamphetamine , biology , neurotoxicity , genetics , medicine , gene , endocrinology , microbiology and biotechnology , biochemistry , enzyme , toxicity
Several lines of evidence suggest that increased generation of auto‐oxidized dopamine (DA) o ‐quinone is associated with the neurotoxicity of methamphetamine (MAP) in the brain, and that, as a cellular defenses against DA‐derived quinines, glutathione S‐transferase (GST) detoxifies auto‐oxidized DA o ‐quinone in the brain. Glutathione S‐transferase M1 (GSTM1) of the mu‐class of GSTs catalyzes reaction between glutathione and catecholamine o ‐quinones under physiological conditions. This study was undertaken to investigate the role of the GSTM1 gene deletion polymorphism in the neuropathology of MAP abuse. One hundred fifty‐seven MAP abusers and 200 healthy comparison subjects were tested for a genetic polymorphism of GSTM1. The difference in the frequency of deletion (D)/non‐deletion (N) alleles between the female abusers and female controls was close to statistical significance ( P = 0.071), although there was no statistical difference ( P = 0.651) between male abusers and male controls. Furthermore, the number of female abusers with deletion alleles was significantly ( P = 0.007, odds ratio: 2.77, 95% CI 1.30–5.89) higher than that of male abusers with deletion alleles. These findings suggest that GSTM1 gene deletion may contribute to a vulnerability to MAP abuse in female subjects, but not in male subjects. © 2003 Wiley‐Liss, Inc.