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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
Author(s) -
Zhang Min,
Wang Shuqiang,
Wilffert Bob,
Tong Rongsheng,
Soolingen Dick,
Hof Susan,
Alffenaar JanWillem
Publication year - 2018
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.13722
Subject(s) - meta analysis , odds ratio , medicine , genotype , population , genetics , biology , environmental health , gene
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, I 2 = 51.3%, P = 0.000). The OR varied between different ethnic populations, ranging from 6.42 (95% CI 2.41–17.10, I 2 = 2.3%) for the West Asian population to 2.32 (95% CI 0.58–9.24, I 2 = 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.