title: Association between the glutathione S-transferase M1 gene deletion and female methamphetamine abusers.
abstract: 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.
authors.affiliation: Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Koizumi
authors.forename: Kenji
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Chikara
authors.initials: C
authors.lastname: Kumakiri
authors.forename: Eiji
authors.initials: E
authors.lastname: Shimizu
authors.forename: Yoshimoto
authors.initials: Y
authors.lastname: Sekine
authors.forename: Norio
authors.initials: N
authors.lastname: Ozaki
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: Mitsuhiko
authors.initials: M
authors.lastname: Yamada
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sora
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ujike
authors.forename: Nori
authors.initials: N
authors.lastname: Takei
authors.forename: Masaomi
authors.initials: M
authors.lastname: Iyo
mesh_terms: D000328:Adult; D000368:Aged; D019969:Amphetamine-Related Disorders / Q000235:genetics*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D005260:Female; D017353:Gene Deletion; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D008875:Middle Aged
chemical_list: D000697:Central Nervous System Stimulants; D005982:Glutathione Transferase; D008694:Methamphetamine