NAT2 variants and toxicity related to anti-tuberculosis agents : a systematic review and meta-analysis
MetadataShow full item record
BACKGROUND : Tuberculosis (TB) patients receiving anti-tuberculosis treatment may experience serious adverse drug reactions (ADRs) such as hepatotoxicity. Variants of the N-acetyltransferase 2 (NAT2) gene may increase the risk of experiencing such toxicity events. OBJECTIVE : To provide a comprehensive evaluation of the evidence base for associations between NAT2 variants and anti-tuberculosis drug-related toxicity. METHOD : This was a systematic review and metaanalysis. We searched for studies in Medline, PubMed, EMBASE, BIOSIS and Web of Science.We included data from 41 articles (39 distinct cohorts of patients). We pooled effect estimates for each genotype on each outcome using meta-analyses stratified by country. RESULTS : We assessed the quality of the included studies, which was variable, with many areas of concern. Slow/intermediate NAT2 acetylators were statistically significantly more likely to experience hepatotoxicity than rapid acetylators (OR 1.59, 95%CI 1.26-2.01). Heterogeneity was not detected in the overall pooled analysis (I2 = 0%). NAT2 acetylator status was significantly associated with the likelihood of experiencing anti-tuberculosis drugrelated hepatotoxicity. CONCLUSION : We encountered several challenges in performing robust syntheses of data from pharmacogenetic studies, and we outline recommendations for the future reporting of pharmacogenetic studies to enable high-quality systematic reviews and meta-analyses to be performed.
Richardson , M , Kirkham , J , Dwan , K , Sloan , D J , Davies , G & Jorgensen , A L 2019 , ' NAT2 variants and toxicity related to anti-tuberculosis agents : a systematic review and meta-analysis ' , International Journal of Tuberculosis and Lung Disease , vol. 23 , no. 3 , pp. 293-305 . https://doi.org/10.5588/ijtld.18.0324
International Journal of Tuberculosis and Lung Disease
Copyright © 2019 The Union. This work has been made available online in accordance with publisher policies or with permission. Permission for further reuse of this content should be sought from the publisher or the rights holder. This is the author created accepted manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at https://doi.org/10.5588/ijtld.18.0324
Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.