title: Slow N-acetyltransferase 2 genotype contributes to anti-tuberculosis drug-induced hepatotoxicity: a meta-analysis.
abstract: Pathogenesis and genetic factors influencing predisposition to antituberculosis drug-induced hepatotoxicity (ATDH) are not clear. Polymorphism at the genetic locus of a drug and xenobiotic compound metabolizing enzyme, N-acetyltransferase type 2 (NAT2), is reported to be associated with the excess generation of toxic reactive metabolites. To date, many case-control studies have been carried out to investigate the relationship between the NAT2 polymorphisms and ATDH, but the results have been inconsistent. To investigate this inconsistency, a meta-analysis was performed. Databases including PubMed, Web of Science, EMBASE and CNKI were searched to find relevant studies. A total of 26 case-control studies, involving 1,198 cases and 2,921 controls were included. Overall, we found significant association between slow acetylator genotype of NAT2 and ATDH (OR = 3.10, 95% CI: 2.47-3.88, P < 10(-5)). Significant results were also found in East Asians, South Asians, Brazilians and Middle Eastern when stratified by ethnicity. However, no significant associations were found for Caucasians. This meta-analysis demonstrated that the slow acetylator genotype of NAT2 is a risk factor associated with increased ATDH susceptibility, but these associations vary in different ethnic populations.
authors.affiliation: Department of Pulmonology, General Hospital of Guangzhou Military Command, 111 Liuhua Road, Guangzhou 510010, People's Republic of China.
authors.forename: Haijian
authors.initials: H
authors.lastname: Du
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Chen
authors.forename: Yi
authors.initials: Y
authors.lastname: Fang
authors.forename: Ouyang
authors.initials: O
authors.lastname: Yan
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Weifeng
authors.initials: W
authors.lastname: Li
authors.forename: Wenjie
authors.initials: W
authors.lastname: Huang
mesh_terms: D000995:Antitubercular Agents / Q000009:adverse effects*; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016017:Odds Ratio
chemical_list: D000995:Antitubercular Agents; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human