Association between the glutathione S-transferase M1 gene deletion and female methamphetamine abusers.
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.
Koizumi
Hiroki
H
Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670, Japan.
Hashimoto
Kenji
K
Kumakiri
Chikara
C
Shimizu
Eiji
E
Sekine
Yoshimoto
Y
Ozaki
Norio
N
Inada
Toshiya
T
Harano
Mutsuo
M
Komiyama
Tokutaro
T
Yamada
Mitsuhiko
M
Sora
Ichiro
I
Ujike
Hiroshi
H
Takei
Nori
N
Iyo
Masaomi
M
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
D000697:Central Nervous System Stimulants; D005982:Glutathione Transferase; D008694:Methamphetamine