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Genetic variants in antioxidant pathway: Risk factors for hepatotoxicity in tuberculosis patients

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Title: Genetic variants in antioxidant pathway: Risk factors for hepatotoxicity in tuberculosis patients
Authors: Nanashima, Kazutaka / Mawatari, Tsutomu / Tahara, Naoko / Higuchi, Norihide / Nakaura, Ayano / Inamine, Tatsuo / Kondo, Shinji / Yanagihara, Katsunori / Fukushima, Kiyoyasu / Suyama, Naofumi / Kohno, Shigeru / Tsukamoto, Kazuhiro
Issue Date: May-2012
Publisher: Elsevier Ltd.
Citation: Tuberculosis, 92(3), pp. 253-259; 2012
Abstract: Tuberculosis (TB) treatment can cause serious sequelae including adverse effects such as anti-TB drug-induced hepatotoxicity (ATDH). We performed a candidate gene-based association study between single nucleotide polymorphisms (SNPs) in 10 genes in the antioxidant pathway and ATDH susceptibility. The subjects comprised 100 Japanese patients with pulmonary TB who received a treatment regimen including isoniazid and rifampicin. Out of them, 18 patients had ATDH. Thirty-four tag SNPs in 10 genes were analyzed by PCR-restriction fragment length polymorphism or PCR-direct DNA sequencing. The frequencies of alleles and genotypes between patients with and without ATDH were compared in three different genetic models. Statistical analyses revealed that a C/C genotype at rs11080344 in NOS2A, a C/C genotype at rs2070401 in BACH1, and a G/A or A/A genotype at rs4720833 in MAFK independently conferred ATDH susceptibility. Remarkably, the association of the latter two tag SNPs with ATDH susceptibility was highly statistically significant (P = 0.0006) with an odds ratio of 9.730. This study is the first report to demonstrate that NOS2A, BACH1, and MAFK appear to be genetic determinants of ATDH in Japanese patients with TB. Furthermore, a combination of BACH1 and MAFK polymorphisms may be useful as new biomarkers to identify high-risk Japanese TB patients for ATDH.
Keywords: Anti-tuberculosis drug-induced hepatotoxicity / Antioxidant pathway / Candidate gene-based association study / Single nucleotide polymorphism (SNP) / Tuberculosis
URI: http://hdl.handle.net/10069/29011
ISSN: 14729792
DOI: 10.1016/j.tube.2011.12.004
Rights: © 2012 Elsevier Ltd. All rights reserved. / NOTICE: this is the author’s version of a work that was accepted for publication in Tuberculosis. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Tuberculosis, 92, 3(2012)
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/29011

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