title: Association between TXNRD1 polymorphisms and anti-tuberculosis drug-induced hepatotoxicity in a prospective study.
abstract: Anti-tuberculosis drug-induced hepatotoxicity (ATDH) is a serious adverse reaction to anti-tuberculosis (TB) treatment. Thioredoxin reductase 1 (TXNRD1), encoded by the TXNRD1 gene, is an important enzyme involved in oxidant challenge. TXNRD1 plays a key role in regulating cell growth and transformation, and protects cells against oxidative damage. We investigated the association between TXNRD1 polymorphisms and ATDH susceptibility. In this prospective study, 280 newly diagnosed TB patients were followed-up for 3 months after beginning anti-TB therapy. Tag single-nucleotide polymorphisms (tag-SNPs) of TXNRD1 were selected using Haploview 4.2 based on the HapMap database of the Chinese Han in Beijing (CHB) panel. Genotyping was performed using the MassARRAY platform. Of the 280 patients enrolled in this study, 33 were lost to follow-up, 24 had ATDH, and 223 were free from ATDH. After adjusting for sex, age, smoking status, and body mass index, there were no significant differences in the allele and genotype frequency distributions of TXNRD1 SNPs between the ATDH and non-ATDH groups (all P > 0.05). The haplotype analysis showed that haplotype TCAGCC was associated with an increased risk of ATDH susceptibility [P = 0.024, OR (95%CI) = 6.273 (1.023-38.485)]. Further stratified analyses showed that the haplotype TCAGCC was associated with ATDH susceptibility in female subjects [P = 0.036, OR (95%CI) = 5.711 (0.917-35.560)] and non-smokers [P = 0.029, OR (95%CI) = 6.008 (0.971-37.158)]. Our results suggest that TXNRD1 variants may favor ATDH susceptibility in females and non-smokers. Further studies are required to verify this association.
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: G Y
authors.initials: GY
authors.lastname: Ji
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: S Q
authors.initials: SQ
authors.lastname: Wu
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Guoxue Alley, Chengdu, Sichuan, China.
authors.forename: Q Q
authors.initials: QQ
authors.lastname: Liu
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: J C
authors.initials: JC
authors.lastname: Wu
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: M M
authors.initials: MM
authors.lastname: Zhang
authors.affiliation: Centre for Heart Lung Innovation, University of British Columbia and St. Paul's Hospital, Vancouver, BC, Canada.
authors.forename: A J
authors.initials: AJ
authors.lastname: Sandford
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China 18980602293@qq.com.
authors.forename: J Q
authors.initials: JQ
authors.lastname: He
mesh_terms: D000328:Adult; D000367:Age Factors; D000483:Alleles; D000995:Antitubercular Agents / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D004977:Ethambutol / Q000009:adverse effects; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D007538:Isoniazid / Q000009:adverse effects; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000254:growth & development; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011718:Pyrazinamide / Q000009:adverse effects; D012293:Rifampin / Q000009:adverse effects; D012307:Risk Factors; D012737:Sex Factors; D054481:Thioredoxin Reductase 1 / Q000235:genetics*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D004977:Ethambutol; C516124:TXNRD1 protein, human; D054481:Thioredoxin Reductase 1; D007538:Isoniazid; D012293:Rifampin