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

Autor: Naoko Tahara, Tatsuo Inamine, Katsunori Yanagihara, Naofumi Suyama, Norihide Higuchi, Kiyoyasu Fukushima, Kazutaka Nanashima, Ayano Nakaura, Tsutomu Mawatari, Shigeru Kohno, Shinji Kondo, Kazuhiro Tsukamoto
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Adult
Male
Microbiology (medical)
Candidate gene
Tuberculosis
Anti-tuberculosis drug-induced hepatotoxicity
Genotype
Immunology
Antitubercular Agents
Nitric Oxide Synthase Type II
Single-nucleotide polymorphism
Biology
Polymorphism
Single Nucleotide
Microbiology
Antioxidant pathway
Young Adult
Gene Frequency
Risk Factors
Polymorphism (computer science)
Single nucleotide polymorphism (SNP)
Genetic model
Isoniazid
medicine
Humans
Genetic Predisposition to Disease
Allele
Tuberculosis
Pulmonary
Allele frequency
Genetic Association Studies
Aged
Aged
80 and over
Genetics
Middle Aged
medicine.disease
MafK Transcription Factor
Fanconi Anemia Complementation Group Proteins
Basic-Leucine Zipper Transcription Factors
Infectious Diseases
Candidate gene-based association study
Drug Therapy
Combination
Female
Chemical and Drug Induced Liver Injury
Rifampin
Oxidation-Reduction
Zdroj: Tuberculosis. 92(3):253-259
ISSN: 1472-9792
Popis: 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.
Tuberculosis, 92(3), pp. 253-259; 2012
Databáze: OpenAIRE
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