title: NAT2 polymorphisms and susceptibility to anti-tuberculosis drug-induced liver injury: a meta-analysis.
abstract: OBJECTIVE
  Although a series of studies have evaluated the potential association between N-acetyltransferase 2 (NAT2) polymorphisms and the risk of anti-tuberculosis drug-induced liver injury (ATLI), the results have generally been controversial and inadequate,  mainly due to limited power. The present meta-analysis sought to resolve this problem.
  
  
  METHODS
  PubMed, Embase and Web of Science were searched using the following key words: 'N-acetyltransferase 2' or 'NAT2' and 'polymorphism' and 'tuberculosis'  or 'TB' and 'hepatotoxicity' or 'liver injury'. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were summarised in forest plots and set out in a table.
  
  
  RESULTS
  A total of 14 studies, comprising 474 cases and 1446 controls, were included in  the meta-analysis. A significant association was observed between NAT2 slow acetylators and the risk of ATLI. The OR for NAT2 slow acetylators compared with rapid acetylators was 4.697 (95%CI 3.291-6.705, P < 0.001). Subgroup analyses indicate that both Asian  and non-Asian cases with slow acetylators develop ATLI more frequently, which is similar to patients with slow acetylators receiving first-line combination treatment. On comparing NAT2 intermediate acetylators with rapid acetylators, the OR for ATLI was 1.261 (95%CI 0.928-1.712,  P = 0.138).
  
  
  CONCLUSIONS
  This meta-analysis showed that tuberculosis patients with slow acetylators had a higher risk of ATLI than other acetylators. Screening of patients for the NAT2 genetic polymorphisms will be useful for the clinical prediction and prevention of ATLI.
authors.affiliation: Binzhou Medical University, Yantai, China.
authors.forename: P-Y
authors.initials: PY
authors.lastname: Wang
authors.forename: S-Y
authors.initials: SY
authors.lastname: Xie
authors.forename: Q
authors.initials: Q
authors.lastname: Hao
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.forename: B-F
authors.initials: BF
authors.lastname: Jiang
mesh_terms: D000995:Antitubercular Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014376:Tuberculosis / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human