Glutathione S-transferase M1 gene deletion may be associated with susceptibility to certain forms of schizophrenia

Recent studies have revealed that GSTM1 and M2 of the mu -class glutathione S-transferases catalyze a glutathione conjugate of catechol o-quinones inc luding dopachrome, noradrenochrome, and adrenochrome under physiological co nditions. Reduced or negative levels of activity amongst these enzymes woul d lead to an excess of neurotoxic compounds of catecholamine o-quinones. A defect in the mechanisms responsible for this form of detoxification may co ntribute to the development of certain forms of schizophrenia. We have perf ormed a case-control study to explore the association between schizophrenia and polymorphism of the GSTM1 gene. DNA samples were obtained from 87 unre lated patients with schizophrenia who met the DSM-IV criteria for schizophr enia and from 176 control subjects. Individuals of both groups were ethnica lly Japanese and were from the same district. GSTM1 polymorphism was determ ined using the polymerase chain reaction method. The frequency of the GSTM1 *0 allele was significantly higher amongst the patients with schizophrenia compared to controls (P = 0.0075), Moreover, the incidence of the GSTM1*O w as significantly higher amongst the schizophrenic patients classified as di sorganized type (P = 0,0008), relative to the control sample. Our findings suggest that the GSTM1*0 is associated with an increased susceptibility to schizophrenia, particularly disorganized type of the disease. It is therefo re likely that the GSTM1 gene deletion constitutes to vulnerability for dis ease states of this kind, rather than being the direct cause of schizophren ic conditions. (C) 2001 Academic Press.