Association between the Glutathione S-transferase M1 gene deletion and female methamphetamine abusers

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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)/nondeletion (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. (C) 2003 Wiley-Liss, Inc.
Wiley-Liss, Inc.の論文
2004-04-01