The association between the NAT2 genetic polymorphisms and risk of DILI during anti‐TB treatment: a systematic review and meta‐analysis

Aims The aim of this study is to evaluate the potential association between N‐acetyltransferase type 2 (NAT2) polymorphisms and drug‐induced liver injury during anti‐TB treatment (AT‐DILI). Methods We conducted a systematic review and performed a meta‐analysis to clarify the role of NAT2 polymorphis...

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Published in:	British journal of clinical pharmacology Vol. 84; no. 12; pp. 2747 - 2760
Main Authors:	Zhang, Min, Wang, Shuqiang, Wilffert, Bob, Tong, Rongsheng, Soolingen, Dick, Hof, Susan, Alffenaar, Jan‐Willem
Format:	Journal Article
Language:	English
Published:	England John Wiley and Sons Inc 01.12.2018
Subjects:	Antitubercular Agents - adverse effects antituberculosis drug‐induced liver injury Arylamine N-Acetyltransferase - genetics Chemical and Drug Induced Liver Injury - etiology Chemical and Drug Induced Liver Injury - genetics Genetic Predisposition to Disease Genotype Humans meta‐analysis NAT2 polymorphism Polymorphism, Genetic Review antituberculosis drug-induced liver injury meta-analysis polymorphism NAT2
ISSN:	0306-5251, 1365-2125, 1365-2125
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Summary:	Aims The aim of this study is to evaluate the potential association between N‐acetyltransferase type 2 (NAT2) polymorphisms and drug‐induced liver injury during anti‐TB treatment (AT‐DILI). Methods We conducted a systematic review and performed a meta‐analysis to clarify the role of NAT2 polymorphism in AT‐DILI. PubMed, Medline and EMBASE databases were searched for studies published in English to December 31, 2017, on the association between the NAT2 polymorphism and AT‐DILI risk. Outcomes were pooled with random‐effects meta‐analysis. Details were registered in the PROSPERO register (number: CRD42016051722). Results Thirty‐seven studies involving 1527 cases and 7184 controls were included in this meta‐analysis. The overall odds ratio (OR) of AT‐DILI associated with NAT2 slow acetylator phenotype was 3.15 (95% CI 2.58–3.84, I2 = 51.3%, P = 0.000). The OR varied between different ethnic populations, ranging from 6.42 (95% CI 2.41–17.10, I2 = 2.3%) for the West Asian population to 2.32 (95% CI 0.58–9.24, I2 = 80.3%) for the European population. Within the slow NAT2 genotype, variation was also observed; NAT26/7 was associated with the highest risk of AT‐DILI (OR = 1.68, 95% CI 1.09–2.59) compared to the other slow NAT2 acetylators combined. Conclusions NAT2 slow acetylation was observed to increase the risk of AT‐DILI in tuberculosis patients. Our results support the hypothesis that the slow NAT2 genotype is a risk factor for AT‐DILI.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3 These authors contributed equally to this work.
ISSN:	0306-5251 1365-2125 1365-2125
DOI:	10.1111/bcp.13722