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

Zhang, M., Wang, S., Wilffert, B., Tong, R., van Soolingen, D., van den Hof, S. & Alffenaar, J-W. 26-Jul-2018 In : British Journal of Clinical Pharmacology. 28 p.

Research output: Contribution to journalReview article

AIMS: 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 1,527 cases and 7,184 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.

Original languageEnglish
Number of pages28
JournalBritish Journal of Clinical Pharmacology
StateE-pub ahead of print - 26-Jul-2018

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