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.
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 tuberculosispatients 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: Yuri F van der Heijden; Fareed Abdullah; Bruno B Andrade; Jason R Andrews; Devasahayam J Christopher; Julio Croda; Heather Ewing; David W Haas; Mark Hatherill; C Robert Horsburgh; Vidya Mave; Helder I Nakaya; Valeria Rolla; Sudha Srinivasan; Retna Indah Sugiyono; Cesar Ugarte-Gil; Carol Hamilton Journal: Tuberculosis (Edinb) Date: 2018-10-01 Impact factor: 3.131
Authors: Daniel J Klein; Sotiria Boukouvala; Ellen M McDonagh; Scott R Shuldiner; Nicola Laurieri; Caroline F Thorn; Russ B Altman; Teri E Klein Journal: Pharmacogenet Genomics Date: 2016-09 Impact factor: 2.089
Authors: Ellen M McDonagh; Sotiria Boukouvala; Eleni Aklillu; David W Hein; Russ B Altman; Teri E Klein Journal: Pharmacogenet Genomics Date: 2014-08 Impact factor: 2.089