Deletion of glutathione S-transferase theta-1 (GSTT1) and anticonvulsant (ACD)—induced hypersensitivity syndrome
Conference Contribution ResearchOnline@JCUAbstract
The use of phenytoin (PHT) and carbamazepine (CBZ) is associated with the development of hypersensitivity reactions in 5–10% of patients. Cytochrome P450-dependent metabolism of these drugs may result in the formation of reactive intermediates, drug-protein adducts and the initiation of drug-induced autoimmune reactions. GSTs are critical enzymes in the conjugation and subsequent detoxification of electrophilic metabolites. We hypothesised that a genetic deletion of polymorphic GSTT1 may be a risk factor in the development of ACD-induced hypersensitivity. Using a PCR-based approach, we genotyped hypersensitive patients and control subjects for GSTT1 and GSTM1. Of the patient group 3/8 (38%) and 5/8 (63%) were null for GSTT1 and GSTM1, respectively, while 1/27 (4%) and 14/27 (52%) control subjects were null for GSTT1 and GSTM1, respectively. Using a one-tailed Fisher’s exact test, the proportion of patients with the GSTT1 defect was found to be significantly higher (P<0.05) than that of control subjects. These results suggest that a deletion of GSTT1 may be associated with the occurrence of PHT- or CBZ-induced hypersensitivity reactions.
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Toxicology
Volume
164
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1
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Brisbane, Australia
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Elsevier
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DOI
10.1016/S0300-483X(01)00386-9