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Updated: Jul 15, 2026

Spectrophotometric Screening for Potential Inhibitors of Cytosolic Glutathione S-Transferases
Published on: October 10, 2020
Glutathione S-transferase M1 null genotype as a risk factor for carbamazepine-induced mild hepatotoxicity
Kentaro Ueda1, Takateru Ishitsu, Takayuki Seo
1Kumamoto University, Division of Pharmacology and Therapeutics, Graduate School of Medical and Pharmaceutical Science, Oe-honmachi 5-1, Kumamoto 862-0973, Japan.
Unlabelled:
The aim of this study is to verify whether the combination of glutathione S-transferase (GST) M1 null and GSTT1 null genotypes, which is a candidate genetic risk factor for troglitazone-induced liver failure, is common to that for the carbamazepine-induced mild hepatotoxicity.
Patients & Methods:
The genotypes of GSTM1 and GSTT1, and microsomal epoxide hydrolase-3 and -4, were determined in 192 Japanese epileptics treated with carbamazepine.
Results:
The GSTM1 null (GSTM1-) and GSTT1 null (GSTT1-) genotypes in the subjects were 55.7 and 39.6%, respectively. The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were elevated in 46 (24.0%) and 62 (32.3%) cases, and the mean values were approximately 2.3- and 1.8-times higher than the upper limit of normal levels, respectively. The levels of ALT and AST were significantly higher in GSTM1- than in GSTM1 present (GSTM1+) genotypes (p = 0.007 and 0.004, respectively). The level of ALT was significantly higher in GSTM1-/T1- than in GSTM1+/T1- and GSTM1+/T1+ (p = 0.01 and 0.01, respectively), and that of AST was significantly higher in GSTM1-/T1- and GSTM1-/T1+ than in GSTM1+/T1+ (p = 0.02 and 0.003, respectively). The microsomal epoxide hydrolase genotype did not influence the hepatotoxicity.
Conclusion:
These findings suggested that GSTM1- rather than GSTM1-/T1- was a risk factor for carbamazepine-induced mild hepatotoxicity.
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