Genetic Polymorphisms in Antioxidant Enzymes Modulate the Susceptibility of Idiosyncratic Antituberculous Drug‐Induced Liver Injury and Treatment Outcomes in Patients with Tuberculosis

2019 ◽  
Vol 40 (1) ◽  
pp. 4-16 ◽  
Author(s):  
Qin Sun ◽  
Wei Sha ◽  
Hai‐peng Liu ◽  
Peng Wang ◽  
Zhi‐bin Liu ◽  
...  
Keyword(s):  
Antioxidant Enzymes ◽  
Liver Injury ◽  
Treatment Outcomes ◽  
Genetic Polymorphisms ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Antituberculous Drug

scholarly journals CYP2E1, GSTM1, and GSTT1 genetic polymorphisms and their associations with susceptibility to antituberculosis drug-induced liver injury in Thai tuberculosis patients

Heliyon ◽  
2021 ◽  
Vol 7 (4) ◽  
pp. e06852
Author(s):  
Noppadol Chanhom ◽  
Sukanya Wattanapokayakit ◽  
Nusara Satproedprai ◽  
Supharat Suvichapanich ◽  
Surakameth Mahasirimongkol ◽  
...  
Keyword(s):  
Liver Injury ◽  
Genetic Polymorphisms ◽  
Antituberculosis Drug ◽  
Drug Induced ◽  
Tuberculosis Patients ◽  
Drug Induced Liver Injury

scholarly journals Association of genetic polymorphisms of CYP2E1, NAT2, GST and SLCO1B1 with the risk of anti-tuberculosis drug-induced liver injury: a systematic review and meta-analysis

BMJ Open ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. e027940 ◽  
Author(s):  
Seungwon Yang ◽  
Se Jung Hwang ◽  
Jung Yun Park ◽  
Eun Kyoung Chung ◽  
Jangik I Lee
Keyword(s):  
Systematic Review ◽  
Liver Injury ◽  
Genetic Polymorphisms ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Organic Anion ◽  
Close Monitoring ◽  
Drug Induced ◽  
Slow Acetylator ◽  
Drug Induced Liver Injury

ObjectivesThe objective of this study was to investigate the association between genetic polymorphisms of N-acetyltransferase 2 (NAT2), cytochrome P450 2E1 (CYP2E1), glutathione S-transferase (GST) and solute carrier organic anion transporter family member 1B1 (SLCO1B1) and the risk of anti-tuberculosis drug-induced liver injury (ATDILI).DesignSystematic review and meta-analysis.Data sourcesPubMed, Embase, Web of Science and Cochrane Reviews databases were searched through April 2019.Eligibility criteriaWe included case-control or cohort studies investigating an association between NAT2, CYP2E1, GST or SLCO1B1 polymorphisms and the ATDILI risk in patients with tuberculosis.Data extraction and synthesisThree authors screened articles, extracted data and assessed study quality. The strength of association was evaluated for each gene using the pooled OR with a 95% CI based on the fixed-effects or random-effects model. Sensitivity analysis was performed to confirm the reliability and robustness of the results.ResultsFifty-four studies were included in this analysis (n=26 for CYP2E1, n=35 for NAT2, n=19 for GST, n=4 for SLCO1B1). The risk of ATDILI was significantly increased with the following genotypes: CYP2E1 RsaI/PstI c1/c1 (OR=1.39, 95% CI 1.06 to 1.83), NAT2 slow acetylator (OR=3.30, 95% CI 2.65 to 4.11) and GSTM1 null (OR=1.30, 95% CI 1.12 to 1.52). No significant association with ATDILI was found for the genetic polymorphisms of CYP2E1 DraI, GSTT1, GSTM1/GSTT1, SLCO1B1 388A>G and SLCO1B1 521T>C (p>0.05).ConclusionsATDILI is more likely to occur in patients with NAT2 slow acetylator genotype, CYP2E1 RsaI/PstI c1/c1 genotype and GSTM1 null genotype. Close monitoring may be warranted for patients with these genotypes.

scholarly journals Genetic Polymorphisms Implicated in Nonalcoholic Liver Disease or Selected Other Disorders Have No Influence on Drug‐Induced Liver Injury

2019 ◽  
Vol 3 (8) ◽  
pp. 1032-1035 ◽  
Author(s):  
Herbert L. Bonkovsky ◽  
Tyler Severson ◽  
Paola Nicoletti ◽  
Huiman Barnhart ◽  
Jose Serrano ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Genetic Polymorphisms ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Nonalcoholic Liver Disease

scholarly journals Association between genetic polymorphisms of NRF2, KEAP1, MAFF, MAFK and anti-tuberculosis drug-induced liver injury: a nested case-control study

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Shixian Chen ◽  
Hongqiu Pan ◽  
Yongzhong Chen ◽  
Lihuan Lu ◽  
Xiaomin He ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signaling Pathway ◽  
Genetic Polymorphisms ◽  
Case Control Study ◽  
Case Control ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Tb Treatment ◽  
Nested Case Control ◽  
Control Study

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.

scholarly journals GSTM1 and GSTT1 genetic polymorphisms and their association with antituberculosis drug‑induced liver injury

2020 ◽  
Author(s):  
Noppadol Chanhom ◽  
Wanvisa Udomsinprasert ◽  
Usa Chaikledkaew ◽  
Surakameth Mahasirimongkol ◽  
Sukanya Wattanapokayakit ◽  
...  
Keyword(s):  
Liver Injury ◽  
Genetic Polymorphisms ◽  
Antituberculosis Drug ◽  
Drug Induced ◽  
Drug Induced Liver Injury
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