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NAT2 polymorphisms and susceptibility to anti-tuberculosis drug-induced liver injury: a meta-analysis

P-Y Wang1, S-Y Xie, Q Hao

  • 1Binzhou Medical University, Yantai, China.

The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease
|March 14, 2012
PubMed
Abstract

Insights

Tuberculosis patients with slow N-acetyltransferase 2 (NAT2) acetylator genotypes have a significantly higher risk of anti-tuberculosis drug-induced liver injury (ATLI). Genetic screening for NAT2 polymorphisms can aid in predicting and preventing ATLI.

Area of Science:

  • Pharmacogenomics
  • Hepatology
  • Infectious Diseases

Background:

  • Anti-tuberculosis drug-induced liver injury (ATLI) is a significant clinical challenge.
  • Previous studies on N-acetyltransferase 2 (NAT2) polymorphisms and ATLI risk have yielded controversial results due to limited statistical power.

Purpose of the Study:

  • To resolve inconsistencies in previous research by conducting a comprehensive meta-analysis.
  • To evaluate the association between NAT2 genetic polymorphisms and the risk of developing ATLI.

Main Methods:

  • A systematic literature search was performed across PubMed, Embase, and Web of Science.
  • Key search terms included 'N-acetyltransferase 2', 'NAT2', 'polymorphism', 'tuberculosis', 'TB', 'hepatotoxicity', and 'liver injury'.
  • Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated and summarized.

Main Results:

  • The meta-analysis included 14 studies with 474 cases and 1446 controls.
  • A significant association was found between NAT2 slow acetylators and increased ATLI risk (OR = 4.697, P < 0.001).
  • Subgroup analyses confirmed higher ATLI incidence in both Asian and non-Asian slow acetylators, and in those receiving first-line treatment.

Conclusions:

  • Tuberculosis patients with NAT2 slow acetylator genotypes face a substantially elevated risk of ATLI.
  • Screening for NAT2 genetic polymorphisms is recommended for clinical prediction and prevention strategies for ATLI.

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