Open Access

GSTM1 and GSTT1 genetic polymorphisms and their association with antituberculosis drug‑induced liver injury

  • Authors:
    • Noppadol Chanhom
    • Wanvisa Udomsinprasert
    • Usa Chaikledkaew
    • Surakameth Mahasirimongkol
    • Sukanya Wattanapokayakit
    • Jiraphun Jittikoon
  • View Affiliations

  • Published online on: February 10, 2020     https://doi.org/10.3892/br.2020.1275
  • Pages: 153-162
  • Copyright: © Chanhom et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Antituberculosis (anti‑TB) drugs are the most common cause of drug‑induced liver injury (DILI). There are numerous studies revealing the associations between the polymorphisms of pharmacogenes and the risk of anti‑TB DILI (ATDILI). In the present study, relevant studies regarding the pharmacogenes associated with ATDILI were systematically searched in PubMed and Scopus. A total of 24 genes associated with ATDILI were reported on and the top five reported genes in terms of frequency were revealed to be N‑acetyltransferase 2, cytochrome P450 family 2 subfamily E member 1, glutathione S‑transferases [glutathione S‑transferase mu 1 (GSTM1) and glutathione S‑transferase theta 1 (GSTT1)] and solute carrier organic anion transporter family member 1B1. As ATDILI may be the result of direct and indirect interactions, the encoded proteins were further analysed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) to observe the protein‑protein interactions and the associations amongst these proteins. The results suggested that only GSTT1 and GSTM1 were central proteins associated with all the other analysed proteins. Therefore, the association between GSTT1 or GSTM1 and the risk of developing ATDILI were further analysed. The results revealed that a GSTM1 deletion genotype was significantly associated with risk of ATDILI [odds ratio (OR), 1.28; 95% confidence interval (CI), 1.08‑1.51; P=0.004], whereas the GSTT1 deletion genotype and GSTM1/GSTT1 dual‑deletion genotype were not significantly associated with risk of ATDILI. Subgroup analysis based on ethnicity was performed and the results demonstrated a significant association between GSTM1 and ATDILI in South Asian individuals (OR, 1.48; 95% CI, 1.12‑1.95; P=0.005), which has not been reported previously, to the best of our knowledge. In conclusion, GSTM1 was associated with ATDILI in South Asian individuals.
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April-2020
Volume 12 Issue 4

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Spandidos Publications style
Chanhom N, Udomsinprasert W, Chaikledkaew U, Mahasirimongkol S, Wattanapokayakit S and Jittikoon J: GSTM1 and GSTT1 genetic polymorphisms and their association with antituberculosis drug‑induced liver injury. Biomed Rep 12: 153-162, 2020
APA
Chanhom, N., Udomsinprasert, W., Chaikledkaew, U., Mahasirimongkol, S., Wattanapokayakit, S., & Jittikoon, J. (2020). GSTM1 and GSTT1 genetic polymorphisms and their association with antituberculosis drug‑induced liver injury. Biomedical Reports, 12, 153-162. https://doi.org/10.3892/br.2020.1275
MLA
Chanhom, N., Udomsinprasert, W., Chaikledkaew, U., Mahasirimongkol, S., Wattanapokayakit, S., Jittikoon, J."GSTM1 and GSTT1 genetic polymorphisms and their association with antituberculosis drug‑induced liver injury". Biomedical Reports 12.4 (2020): 153-162.
Chicago
Chanhom, N., Udomsinprasert, W., Chaikledkaew, U., Mahasirimongkol, S., Wattanapokayakit, S., Jittikoon, J."GSTM1 and GSTT1 genetic polymorphisms and their association with antituberculosis drug‑induced liver injury". Biomedical Reports 12, no. 4 (2020): 153-162. https://doi.org/10.3892/br.2020.1275