Genetic Variants of the Nuclear Factor Erythroid 2-Related Factor 2/Antioxidant Reaction Element Pathway on the Risk of Antituberculosis Drug-Induced Liver Injury: A Systematic Review

Abstract

Aim: To evaluate the effects of genetic variants in the nuclear factor erythroid 2-related factor 2/antioxidant reaction element signaling pathway on antituberculosis drug-induced liver injury (AT-DILI) susceptibility. Methods: The PubMed, Embase, Cochrane, Web of Science, China National Knowledge Infrastructure and Wanfang databases were searched from inception to April 2022. Results: Seven case–control studies with 4676 patients were included. Six genes with 35 SNPs in the pathway have been reported. Among 17 SNPs reported in two or more studies, the meta-analysis indicated that only one SNP (rs3735656 in MAFK) was significantly associated with a decreased risk for AT-DILI under the dominant model (odds ratio: 0.636; 95% CI: 0.519–0.780; p < 0.001). Conclusion: SNP rs3735656 in the MAFK gene was significantly associated with the risk of AT-DILI.

Keywords::

• antituberculosis drug-induced liver injury
• genetic variants
• meta-analysis
• Nrf2/ARE pathway

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/pgs-2023-0040

Author contributions

ZL Hao and ML Zhang contributed equally to this manuscript. ZL Hao and ML Zhang designed the search strategy and performed the literature search; XY Chen and M Zhu extracted and examined the data; B Han and YW He evaluated the quality of literature. ZL Hao and ML Zhang analyzed and interpreted the data and drafted the manuscript. HG Yi and SW Tang conceived and designed the study, interpreted the data, revised the manuscript and supervised the quality of the study throughout the conduct of the project. All authors have approved the final draft submitted.

Acknowledgments

The authors would like to thank all the authors whose articles are referenced in this study.

Data sharing statement

The data supporting the findings of this study are included within the main manuscript and the supplemental files. All data generated and analyzed in the study are available from the corresponding author upon reasonable request.

Financial & competing interests disclosure

This study was funded by a grant from the National Natural Science Foundation of China (grant no. 82073614). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This study was funded by a grant from the National Natural Science Foundation of China (grant no. 82073614). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.