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  • 1
    Online Resource
    Online Resource
    The A/A Genotype of XPO1 rs4430924 Is Associated With Higher Risk of Antituberculosis Drug‐Induced Hepatotoxicity in Chinese Patients
    Wiley ; 2019
    In:  The Journal of Clinical Pharmacology Vol. 59, No. 7 ( 2019-07), p. 1014-1021
    Details
    In: The Journal of Clinical Pharmacology, Wiley, Vol. 59, No. 7 ( 2019-07), p. 1014-1021
    Abstract: Antituberculosis (anti‐TB) drug‐induced hepatotoxicity may be related to the excessive reactive oxygen species induced by hepatotoxic metabolites. Antioxidant activity involves the nuclear factor erythroid 2‐related factor 2 (Nrf2) signaling pathway. The BTB domain and CNC homologue 1 (Bach1) may compete with Nrf2 for binding to transcriptional enhancers. Elimination of Bach1‐mediated transcriptional repression depends on nuclear exporter exportin 1 (Xpo1). Thus, Xpo1 may indirectly affect antioxidant activity. The present study aimed to examine the role of tag single‐nucleotide polymorphisms in XPO1 in Chinese anti‐TB treatment patients. A 1:2 matched case‐control study was conducted using 314 anti‐TB drug‐induced hepatotoxicity cases and 628 controls. After correcting for weight and hepatoprotectant use, conditional logistic regression analysis showed that patients carrying the AA genotype of rs4430924 in XPO1 were at higher risk of anti‐TB drug‐induced hepatotoxicity than those carrying the GG genotype based on the subgroup of probable cases (adjusted OR, 1.938; 95%CI, 1.035‐3.628; P = .039), and marginally significant differences were also found under the recessive model ( P = .048) and the additive model ( P = .047). Based on this 1:2 matched case‐control study, the AA genotype of rs4430924 in XPO1 may be associated with higher risk of anti‐TB drug‐induced hepatotoxicity in Chinese anti‐TB treatment patients. Further studies in larger and more varied populations are required to validate this relationship.
    Type of Medium: Online Resource
    ISSN: 0091-2700 , 1552-4604
    URL: Issue
    URL: Article
    DOI: 10.1002/jcph.v59.7
    DOI: 10.1002/jcph.1398
    RVK:
    XA 52835
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2010253-7
    SSG: 15,3
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  • 2
    Online Resource
    Online Resource
    Home-based Anti-Tuberculosis Treatment Adverse Reactions (HATTAR) study: a protocol for a prospective observational study
    BMJ ; 2019
    In:  BMJ Open Vol. 9, No. 3 ( 2019-03), p. e027321-
    Details
    In: BMJ Open, BMJ, Vol. 9, No. 3 ( 2019-03), p. e027321-
    Abstract: Tuberculosis (TB) continues to be an important public health problem throughout much of the world. Drug treatment is the only effective treatment method, but adverse drug events (ADEs) and adverse drug reactions (ADRs) can affect medication adherence. As the number of drug-resistant TB patients and the number of anti-TB drugs have increased, it is necessary to explore the risk factors for ADEs/ADRs to reduce their occurrence. This study aims to build a home-based anti-TB treatment cohort and to recognise the incidences, prognosis and risk factors of anti-TB drug-induced ADEs/ADRs in real-world experiences. Methods and analysis This study is a multicentre, prospective observational cohort study. The study population will consist of 3200 newly diagnosed TB patients between January 2019 and December 2020. After initiating the anti-TB treatment, all patients will be followed up until finishing treatment unless they withdraw, and we will record personal drug use and signs and/or symptoms of discomfort. Patients will receive scheduled laboratory tests in designated hospitals every 2 weeks during the first 2 months, and the residual blood sample after conducting the laboratory tests will be preserved. The ADEs/ADRs will be placed into eight categories: liver dysfunction, gastrointestinal reactions, drug allergy, arthralgia or muscle pain, nervous system disorders, haematological system disorders, renal impairment and others. Ethics and dissemination This study protocol has been approved by the ethics committees of Nanjing Medical University. All patients will give written informed consent before enrollment. The findings of the study will be published in peer-reviewed journals and will be presented at national and international conferences.
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    URL: Article
    DOI: 10.1136/bmjopen-2018-027321
    Language: English
    Publisher: BMJ
    Publication Date: 2019
    detail.hit.zdb_id: 2599832-8
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  • 3
    Online Resource
    Online Resource
    Association between genetic polymorphisms of NRF2, KEAP1, MAFF, MAFK and anti-tuberculosis drug-induced liver injury: a nested case-control study
    Springer Science and Business Media LLC ; 2019
    In:  Scientific Reports Vol. 9, No. 1 ( 2019-10-04)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2019-10-04)
    Abstract: Reactive metabolites of anti-tuberculosis (anti-TB) drugs can result in excessive reactive oxygen species (ROS), which are responsible for drug-induced liver injury. The nuclear factor erythroid 2-related factor 2 (Nrf2) - antioxidant response elements (ARE) (Nrf2-ARE) signaling pathway plays a crucial role in protecting liver cells from ROS, inducing enzymes such as phase II metabolizing enzymes and antioxidant enzymes. Based on a Chinese anti-TB treatment cohort, a nested case-control study was performed to explore the association between 13 tag single-nucleotide polymorphisms (tagSNPs) in the NRF2 , KEAP1 , MAFF , MAFK genes in Nrf2-ARE signaling pathway and the risk of anti-TB drug-induced liver injury (ATLI) in 314 cases and 628 controls. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) after adjusting weight and usage of hepatoprotectant. Patients carrying the TC genotype at rs4243387 or haplotype C-C (rs2001350-rs6726395) in NRF2 were at an increased risk of ATLI (adjusted OR = 1.362, 95% CI: 1.017–1.824, P = 0.038; adjusted OR = 2.503, 95% CI: 1.273–4.921, P = 0.008, respectively), whereas patients carrying TC genotype at rs2267373 or haplotype C-G-C (rs2267373-rs4444637-rs4821767) in MAFF were at a reduced risk of ATLI (adjusted OR = 0.712, 95% CI: 0.532–0.953, P = 0.022; adjusted OR = 0.753, 95% CI: 0.587–0.965, P = 0.025, respectively). Subgroup analysis also detected a significant association between multiple tagSNPs (rs4821767 and rs4444637 in MAFF , rs4720833 in MAFK ) and specific clinical patterns of liver injury under different genetic models. This study shows that genetic polymorphisms of NRF2 , MAFF and MAFK may contribute to the susceptibility to ATLI in the Chinese anti-TB treatment population.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-019-50706-y
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2615211-3
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  • 4
    Online Resource
    Online Resource
    Relevance of NAT2 genotype to anti‐tuberculosis drug‐induced hepatotoxicity in a Chinese Han population
    Wiley ; 2019
    In:  The Journal of Gene Medicine Vol. 21, No. 6 ( 2019-06)
    Details
    In: The Journal of Gene Medicine, Wiley, Vol. 21, No. 6 ( 2019-06)
    Abstract: Anti‐tuberculosis drug‐induced hepatotoxicity (ATDH) is a serious adverse drug reaction. The slow acetylator status of N ‐acetyl transferase 2 (NAT2) is a well‐established risk factor for ATDH. One novel tagging single nucleotide polymorphism (tagging SNP), rs1495741, in NAT2 has been found to be highly predictive of the NAT2 phenotype. The present study aimed to validate the relationships between tagging SNP rs1495741 and ATDH in a Chinese Han population. Methods A 1:2 matched case–control study was conducted using 235 ATDH cases and 470 controls. Conditional or unconditional logistic regression analysis was used to estimate the association between genotypes and the risk of ATDH according to the odds ratio (OR) with a 95% confidence interval (CI). Results Patients carrying the AA genotype of tagging SNP rs1495741 were at higher risk of ATDH than those carrying the GG genotype (OR = 1.653, 95% CI = 1.050–2.601; p  = 0.030). Subgroup analysis suggested that the AA genotype was a risk factor for ATDH in patients aged older than 50 years (OR = 2.486, 95% CI = 1.313–4.706; p  = 0.005), weighing over 50 kg (OR = 1.757, 95% CI = 1.016–3.038; p  = 0.044) or using a hepatoprotectant (OR = 1.611, 95% CI = 1.009–2.572; p  = 0.046). Tagging SNP rs1495741 was not a significant risk factor for moderate and severe hepatotoxicity but appears to be relevant to risk of mild hepatotoxicity specifically. Conclusions The present study is the first to validate the relationships between the tagging SNP rs1495741 and ATDH in a Chinese population. Based on this case–control study, the NAT2 rs1495741 polymorphism is a risk factor for mild but not more severe ATDH in Chinese Han patients.
    Type of Medium: Online Resource
    ISSN: 1099-498X , 1521-2254
    URL: Issue
    URL: Article
    DOI: 10.1002/jgm.v21.6
    DOI: 10.1002/jgm.3096
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2002203-7
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Association between NR1I2 polymorphisms and susceptibility to anti-tuberculosis drug-induced hepatotoxicity in an Eastern Chinese Han population: A case-control study
    Elsevier BV ; 2020
    In:  Infection, Genetics and Evolution Vol. 83 ( 2020-09), p. 104349-
    Details
    In: Infection, Genetics and Evolution, Elsevier BV, Vol. 83 ( 2020-09), p. 104349-
    Type of Medium: Online Resource
    ISSN: 1567-1348
    URL: Article
    DOI: 10.1016/j.meegid.2020.104349
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2057622-5
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    Association of FAM65B, AGBL4, and CUX2 genetic polymorphisms with susceptibility to antituberculosis drug-induced hepatotoxicity : validation study in a Chinese Han population
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Pharmacogenetics and Genomics Vol. 29, No. 4 ( 2019-06), p. 84-90
    Details
    In: Pharmacogenetics and Genomics, Ovid Technologies (Wolters Kluwer Health), Vol. 29, No. 4 ( 2019-06), p. 84-90
    Type of Medium: Online Resource
    ISSN: 1744-6872
    URL: Article
    DOI: 10.1097/FPC.0000000000000370
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 2048376-4
    SSG: 15,3
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