GLUTATHIONE-S-TRANSFERASE-MU GENOTYPE (GSTM1-ASTERISK-0) IN ALZHEIMERS PATIENTS WITH TACRINE TRANSAMINITIS

1 Tacrine (1,2,3,4-tetrahydro-9-aminoacridine) which is used in Alzhei mer's disease, causes elevation of liver transaminases ('tacrine trans aminitis') in 40-50% of patients. This may be related to the formation of a chemically reactive metabolite from tacrine, which can be detoxi fied in vitro by glutathione. 2 Glutathione-S-transferase mu (GSTM1), a detoxication enzyme, is polymorphically expressed being absent in ab out 50% of patients, Its role in the detoxication of the reactive meta bolite of tacrine is not known. 3 The frequency of the enzyme deficien cy (GSTM10) has been investigated in patients with tacrine transamini tis using polymerase chain reaction (PCR) to determine whether the GST M1 status can be used as an absolute predictive factor for susceptibil ity to tacrine transaminitis. 4 The frequency of the GSTM10 genotype in patients with tacrine transaminitis (n = 33; 45.5%) was not signifi cantly different from that in patients treated with tacrine without li ver dysfunction (n = 37; 43%), and when compared with all the controls used in the study (n = 167; 56%). 5 The frequency of the GSTM10 geno type in patients with Alzheimer's disease (n = 79; 46%) was not signif icantly different from that in healthy volunteers (n = 121; 59.5%). 6 Our results indicate that the GSTM1 status cannot be used clinically t o predict individual susceptibility to tacrine transaminitis, and that patients with the GSTM10 genotype are unlikely to have an increased risk of tacrine-induced liver damage. Furthermore, the GSTM1 status wa s not associated with Alzheimer's disease.