Glutathione S-transferase M1 and T1 polymorphisms and the risk of mild hepatotoxicity induced by carbamazepine in a tunisian population study

Abstract

BackgroundThe aim of this study was to evaluate whether the glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) null alleles may contribute to carbamazepine-induced hepatotoxicity.MethodsA cross-sectional prospective study was conducted to identify the frequency distribution of GSTM1 and GSTT1 alleles in 129 Tunisian epileptic patients treated with carbamazepine. Null alleles were determined using a Polymerase Chain Reaction. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured by standard methods.ResultsOur results showed that the frequencies of GSTM1 (−) null allele and GSTT1 null (−) allele were 74.4 and 17.8% respectively. The ALT and AST levels were elevated in 46 (35.7%) and 33 (25.6%) cases. The mean values of ALT and AST were approximately 1.32 and 3.61 times higher than the upper limit of normal levels, respectively. The values of ALT and AST were significantly higher in GSTM1 (−) allele than in GSTM1 (+) (p = 10−3.and 0.004, respectively).The level of ALT was significantly higher in combination of GSTM1 (−)/T1(−) than in combined GSTM1(−)/T1(+) and combined GSTM1(+)/T1(+) (p = 0.2 and 0.03, respectively), and that of AST was significantly higher in combination of GSTM1(−)/T1(−) and in combination of GSTM1(+)/T1(−) than in combination of GSTM1(+)/T1(+) (p = 10−3 and 10−3, respectively).ConclusionsOur findings suggest that the GSTM1 (−) allele may be considered as a key factor for the development of carbamazepine-induced hepatotoxicity. Results related to GSTT (−) allele and elevation in AST levels should be considered with caution as AST may be elevated in other pathophysiological conditions.

A comprehensive platform for analyzing longitudinal multi-omics data

“…Among the top ten inter-donor variable genes (ICC: 58–89%, Fig. 2g ), XIST, ZNF705D, GTF2IRD2, and USP32P2 have differential expression between ovary and prostate/testis; RHD encodes a key protein in the Rh blood group system; and GSTM1 belongs to a highly polymorphic supergene family and affects heterogeneous response to toxicity 25 . These genes appeared to capture more diverse types of differences among donors than their counterparts from scRNA-seq data.…”

Polymorphism of Glutathione S-transferase Genes and the Risk of Toxic Liver Damage in Petrochemical Workers

“…The presence of two null alleles of the GSTM1 gene leads to the absence of the protein product of this gene, which contributes to the development of oxidative stress, causes an increase in the level of DNA adducts and can provoke the development of various liver pathologies. 11,12 A number of research findings show its important prognostic significance in the development of occupational diseases. 13,14 In contrast to these results, our study showed that there was no significant difference in the distribution of the GSTM1 gene genotypes among workers depending on the presence or absence of occupational pathology.…”

Pharmacogenetics in Primary Headache Disorders

“…Both glutathione S-transferase class M1 (GSTM1) and class T1 (GSTT1) are involved in conjugation reactions of the main metabolite and also in the detoxification of toxic metabolites of CBZ ( Bu et al, 2005 ). Findings in 129 Tunisian epileptic patients treated with CBZ suggest that the GSTM1 (-) allele may be considered as a risk factor for CBZ-induced hepatotoxicity ( Chbili et al, 2018 ). Japanese researchers observed a link between the lack of GSTM1 and increased levels of hepatic enzymes in 192 patients treated with CBZ and in 149 patients treated with valproate sodium ( Ueda et al, 2007 ; Fukushima et al, 2008 ).…”