Frequency of null genotypes of glutathione S-transferase M1 and T1 in Japanese patients with drug-induced liver injury.

Abstract

AIM:

Previous reports suggest that the null genotype (*0/*0) of glutathione S-transferase (GST) M1 and/or GSTT1 could be risk factors for drug-induced liver injury (DILI). However, multi-institutional pharmacogenetic research with various suspected drugs has rarely been performed in Japan. Therefore, the aim of this study was to investigate the role of GSTM1 and GSTT1 null genotype in the occurrence of DILI in Japanese patients.

METHODS:

Blood samples of 270 DILI patients from 23 hospitals throughout Japan collected between 2010 and 2018 were subjected to genotyping of null genotypes of GSTM1 and GSTT1 using the SmartAmp-2 method. We also collected information on DILI types, time to onset of DILI, pharmacological classification of suspected drugs and Digestive Disease Week-Japan score, as well as genotypes of GSTM1 and GSTT1 in each patient with DILI.

RESULTS:

The distribution of a combination of null genotypes of GSTM1 and GSTT1 in Japanese patients with DILI was significantly different from that reported in the general Japanese population. Notably, the incidence of the GSTM1 null genotype in patients with DILI was significantly higher than that of the control population. A significant relationship between the frequency of GSTM1 and GSTT1 null genotypes and pharmacological classification of suspected drugs, clinical laboratory data for liver function, time to onset of DILI, and Digestive Disease Week-Japan scores was not observed.

CONCLUSIONS:

The GSTM1 null genotype was associated with an increased incidence of DILI in Japanese patients.

• Authors: Kazuya Maeda, Hajime Takikawa, Mitsuhiko Aiso, Kenji Tsuji, Tatehiro Kagawa, Masaaki Watanabe, Ken Sato, Shotaro Sakisaka, Yoichi Hiasa, Yoshiyuki Takei, Hiromasa Ohira, Etsuko Hashimoto, Minoru Ayada, Tadashi Ikegami, Noriaki Arakawa, Hiroyuki Kusuhara, Yoshiro Saito, Yuichi Sugiyama
• Journal: Hepatology research : the official journal of the Japan Society of Hepatology (Hepatol Res) Vol. 52 Issue 10 Pg. 882-887 (Oct 2022) ISSN: 1386-6346 [Print] Netherlands
• PMID: 35834381 (Publication Type: Journal Article)
• Copyright: © 2022 Japan Society of Hepatology.