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

Abstract

AimsThe 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).MethodsWe 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).ResultsThirty‐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.

The association between NAT2 acetylator status and adverse drug reactions of sulfasalazine: a systematic review and meta-analysis

“…The present results are consistent with those of several previous meta-analyses, which assessed the association between NAT2 acetylator status and anti-tuberculosis drug-induced liver injury (AT-DILI) [34][35][36][37] . According to these studies, NAT2 SAs were associated with an increased risk of AT-DILI.…”

Association between genetic polymorphisms of SLCO1B1 and susceptibility to methimazole‐induced liver injury

“…With the rapid development of gene sequencing technique, a number of specific genetic risk factors have been linked to drug‐induced liver injury (DILI) . These studies provided strong support for using genetic variants as biomarkers for the susceptibility to a given drug‐induced hepatotoxicity .…”

“…With the rapid development of gene sequencing technique, a number of specific genetic risk factors have been linked to drug-induced liver injury (DILI). [10][11][12][13][14][15] These studies provided strong support for using genetic variants as biomarkers for the susceptibility to a given drug-induced hepatotoxicity. 16 As the drug metabolism plays an important role in both detoxification and toxification, the identification of genetic polymorphisms in the drug-metabolizing enzymes has received much attention.…”

Genome‐Wide Analysis of DNA Methylation and Antituberculosis Drug‐Induced Liver Injury in the Han Chinese Population

“…The majority of these identified genes are involved in the pathways of drug absorption, distribution, metabolism, and excretion (ADME), acquired immunity, innate immune responses, cellular repair, etc . For example, the haplotypes of the metabolic‐enzyme‐encoding genes CYP2E1(c1/c1) , NAT2 *6 , and GSM1(null) were reported to decrease the catalytic activity of these important enzymes and increase the probability of ATLI occurrence. In particular, the haplotype of the drug‐transporter‐encoding gene SLCO1B1*15 and BSEP was demonstrated to be associated with a higher risk of ATLI in the Han Chinese population .…”