NAT2 6A, a Haplotype of the N-acetyltransferase 2 Gene, is an Important Biomarker for Risk of Anti-tuberculosis Drug-induced Hepatotoxicity in Japanese Patients with Tuberculosis

Overview

Journal World J Gastroenterol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2007 Nov 21

PMID 18023090

Citations 23

Authors

Norihide Higuchi

Naoko Tahara

Katsunori Yanagihara

Kiyoyasu Fukushima

Naofumi Suyama

Yuichi Inoue

Yoshitsugu Miyazaki

Tsutomu Kobayashi

Kohichiro Yoshiura

Norio Niikawa

Chun-Yang Wen

Hajime Isomoto

Saburou Shikuwa

Katsuhisa Omagari

Yohei Mizuta

Shigeru Kohno

Kazuhiro Tsukamoto

Affiliations

Soon will be listed here.

Abstract

Aim: To investigate an association between N-acetyltransferase 2 (NAT2)-haplotypes/diplotypes and adverse effects in Japanese pulmonary tuberculosis patients.

Methods: We studied 100 patients with pulmonary TB treated with anti-TB drugs including INH. The frequencies and distributions of single nucleotide polymorphisms, haplotypes, and diplotypes of NAT2 were determined by the PCR-restriction fragment length polymorphism method, and the results were compared between TB patients with and without adverse effect, using multivariate logistic regression analysis.

Results: Statistical analysis revealed that the frequency of a variant haplotype, NAT2 6A, was significantly increased in TB patients with hepatotoxicity, compared with those without hepatotoxicity [P = 0.001, odds ratio (OR) = 3.535]. By contrast, the frequency of a wild-type (major) haplotype, "NAT2 4", was significantly lower in TB patients with hepatotoxicity than those without hepatotoxicity (P < 0.001, OR = 0.265). There was no association between NAT2-haplotypes and skin rash or eosinophilia.

Conclusion: The present study shows that NAT2 is one of the determinants of anti-TB drug-induced hepatotoxicity. Moreover, the haplotypes, NAT2 4 and NAT2 6A, are useful new biomarkers for predicting anti-TB drug-induced hepatotoxicity.

Citing Articles

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