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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.
Digital Object Identifer:10.1002/ajmg.b.20148
Published with permission from the copyright holder. This is the author's copy, as published in American Journal of Medical Genetics Part B, Neuropsychiatric Genetics, Apr 2004, Volume 126B, Issue 1, Pages 43-45.
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Copyright © 2003 Wiley-Liss, Inc. All rights reserved.
American Journal of Medical Genetics Part B, Neuropsychiatric Genetics
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