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Meta-Analysis
. 2018 Jul;28(7):167-176.
doi: 10.1097/FPC.0000000000000339.

NAT2 Ultra-Slow Acetylator and Risk of Anti-Tuberculosis Drug-Induced Liver Injury: A Genotype-Based Meta-Analysis

Affiliations
Meta-Analysis

NAT2 Ultra-Slow Acetylator and Risk of Anti-Tuberculosis Drug-Induced Liver Injury: A Genotype-Based Meta-Analysis

Supharat Suvichapanich et al. Pharmacogenet Genomics. .

Abstract

Background: NAT2 slow acetylator is a confirmed risk of anti-tuberculosis drug-induced liver injury (ATDILI). However, NAT2 ultra-slow acetylators, a new refinement among NAT2 slow acetylators, have been recently proposed. The patients with NAT2 genotypes of *6A/*6A, *6A/*7B and *7B/*7B are referred to in this group.

Objective: We aim to prove an association of the NAT2 ultra-slow acetylators with the risk of ATDILI.

Materials and methods: Systematic review and meta-analysis were performed based on each NAT2 genotype and risk of ATDILI cases and also new classification of the ultra-slow acetylators up to 31 October 2016. Meta-analysis of 18 studies with 822 ATDILI cases and 4630 controls was carried out in the RevMan software, version 5.3 with fixed-effect (low heterogeneity) and random effect (moderate to high heterogeneity) methods.

Results: The strong associations between each NAT2 slow acetylator genotypes and ATDILI were confirmed in meta-analysis except for NAT2*5B/*5B [odds ratio (OR): 1.69; 95% confidence interval (CI): 0.96-2.95; P=0.0679]. The NAT2 ultra-slow acetylators contribute to higher risk of ATDILI (OR: 3.60; 95% CI: 2.30-5.63; P=1.76E-08) than all NAT2 slow acetylators (OR: 2.80; 95% CI: 2.20-3.57; P=5.73E-18) as well as fast acetylators. Additional in-vitro study using isoniazid as a substrate supports the existence of ultra-slow acetylator alleles (NAT2*6A and NAT2*7B).

Conclusion: This is the first meta-analysis of NAT2 and the risk of ATDILI at the genotypic level. The result demonstrated that NAT2 ultra-slow acetylator genotypes will have the most effect on the increased risk of ATDILI.

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