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Slow N-acetyltransferase 2 genotype contributes to anti-tuberculosis drug-induced hepatotoxicity: a meta-analysis

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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.

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Authors and Affiliations

  1. Department of Pulmonology, General Hospital of Guangzhou Military Command, 111 Liuhua Road, Guangzhou, 510010, People’s Republic of China

    Haijian Du, Xiaorong Chen, Yi Fang, Ouyang Yan, Hong Xu, Li Li, Weifeng Li & Wenjie Huang

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  1. Haijian Du
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  2. Xiaorong Chen
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  3. Yi Fang
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  4. Ouyang Yan
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  5. Hong Xu
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  6. Li Li
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  7. Weifeng Li
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  8. Wenjie Huang
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Correspondence to Weifeng Li or Wenjie Huang.

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Haijian Du and Xiaorong Chen contributed equally to this work.

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Du, H., Chen, X., Fang, Y. et al. Slow N-acetyltransferase 2 genotype contributes to anti-tuberculosis drug-induced hepatotoxicity: a meta-analysis. Mol Biol Rep 40, 3591–3596 (2013). https://doi.org/10.1007/s11033-012-2433-y

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  • DOI: https://doi.org/10.1007/s11033-012-2433-y

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