Association of genetic polymorphisms of and with the risk of anti-tuberculosis drug-induced liver injury: a systematic review and meta-analysis.

OBJECTIVES

The objective of this study was to investigate the association between genetic polymorphisms of N-acetyltransferase 2 (, cytochrome P450 2E1 (, glutathione S-transferase ( and solute carrier organic anion transporter family member 1B1 ( and the risk of anti-tuberculosis drug-induced liver injury (ATDILI).

DESIGN

Systematic review and meta-analysis.

DATA SOURCES

PubMed, Embase, Web of Science and Cochrane Reviews databases were searched through April 2019.

ELIGIBILITY CRITERIA

We included case-control or cohort studies investigating an association between or polymorphisms and the ATDILI risk in patients with tuberculosis.

DATA EXTRACTION AND SYNTHESIS

Three authors screened articles, extracted data and assessed study quality. The strength of association was evaluated for each gene using the pooled OR with a 95% CI based on the fixed-effects or random-effects model. Sensitivity analysis was performed to confirm the reliability and robustness of the results.

RESULTS

Fifty-four studies were included in this analysis (n=26 for , n=35 for , n=19 for , n=4 for ). The risk of ATDILI was significantly increased with the following genotypes: II c1/c1 (OR=1.39, 95% CI 1.06 to 1.83), slow acetylator (OR=3.30, 95% CI 2.65 to 4.11) and null (OR=1.30, 95% CI 1.12 to 1.52). No significant association with ATDILI was found for the genetic polymorphisms of I, , , 388A>G and 521T>C (p>0.05).

CONCLUSIONS

ATDILI is more likely to occur in patients with slow acetylator genotype, genotype and null genotype. Close monitoring may be warranted for patients with these genotypes.