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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Veröffentlicht in:British journal of clinical pharmacology Jg. 84; H. 12; S. 2747 - 2760
Hauptverfasser: Zhang, Min, Wang, Shuqiang, Wilffert, Bob, Tong, Rongsheng, Soolingen, Dick, Hof, Susan, Alffenaar, Jan‐Willem
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England John Wiley and Sons Inc 01.12.2018
Schlagworte:
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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Zusammenfassung: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; NAT2*6/*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.
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These authors contributed equally to this work.
ISSN:0306-5251
1365-2125
1365-2125
DOI:10.1111/bcp.13722