Association of genetic polymorphisms of <i>CYP2E1, NAT2, GST</i> and <i>SLCO1B1</i> with the risk of anti-tuberculosis drug-induced liver injury: a systematic review and meta-analysis.

Abstract

The objective of this study was to investigate the association between genetic polymorphisms of N-acetyltransferase 2 (<i>NAT2)</i>, cytochrome P450 2E1 (<i>CYP2E1)</i>, glutathione S-transferase (<i>GST)</i> and solute carrier organic anion transporter family member 1B1 (<i>SLCO1B1)</i> and the risk of anti-tuberculosis drug-induced liver injury (ATDILI). Systematic review and meta-analysis. PubMed, Embase, Web of Science and Cochrane Reviews databases were searched through April 2019. We included case-control or cohort studies investigating an association between <i>NAT2, CYP2E1, GST</i> or <i>SLCO1B1</i> polymorphisms and the ATDILI risk in patients with tuberculosis. 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. Fifty-four studies were included in this analysis (n=26 for <i>CYP2E1</i>, n=35 for <i>NAT2</i>, n=19 for <i>GST</i>, n=4 for <i>SLCO1B1</i>). The risk of ATDILI was significantly increased with the following genotypes: <i>CYP2E1 Rsa</i>I<i>/Pst</i>I c1/c1 (OR=1.39, 95% CI 1.06 to 1.83), <i>NAT2</i> slow acetylator (OR=3.30, 95% CI 2.65 to 4.11) and <i>GSTM1</i> null (OR=1.30, 95% CI 1.12 to 1.52). No significant association with ATDILI was found for the genetic polymorphisms of <i>CYP2E1 Dra</i>I, <i>GSTT1</i>, <i>GSTM1/GSTT1</i>, <i>SLCO1B1</i> 388A>G and <i>SLCO1B1</i> 521T>C (p>0.05). ATDILI is more likely to occur in patients with <i>NAT2</i> slow acetylator genotype, <i>CYP2E1 RsaI/PstI c1/c1</i> genotype and <i>GSTM1</i> null genotype. Close monitoring may be warranted for patients with these genotypes.