NAT2 polymorphisms and susceptibility to anti-tuberculosis drug-induced liver injury: a meta-analysis [Review article]
Abstract:BACKGROUND AND 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.
DESIGN: 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.
Document Type: Research Article
Affiliations: 1: Binzhou Medical University, Yantai, China; School of Public Health, Shandong University, Jinan, China 2: Binzhou Medical University, Yantai, China 3: Binzhou Central Hospital, Binzhou, China 4: School of Public Health, Shandong University, Jinan, China
Publication date: May 1, 2012
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