Roles of and polymorphisms in the susceptibility to antituberculosis drug-induced liver injury in China: a case‒control study.

Objective: The pathogenesis of antituberculosis drug-induced liver injury (AT-DILI) remains largely unknown. The current investigation aimed to determine the genetic contribution of the nuclear receptor subfamily 1 Group I member 3 () and nuclear receptor subfamily 1 Group H member 4 () genes to the risk of AT-DILI in the Chinese population.

Methods: A 1:4 matched case‒control study was conducted, and five single nucleotide polymorphisms (SNPs) in the and genes were detected and assessed.

Association of Gene Polymorphisms and Serum Levels of ALAS1 with the Risk of Anti-Tuberculosis Drug-Induced Liver Injury.

The accumulation of protoporphyrin IX in the liver caused by isoniazid and rifampicin through the disorder of heme biosynthesis was considered an important mechanism of anti-tuberculosis drug-induced liver injury (ATLI). Alanine synthase 1 (ALAS1) is a rate-limiting enzyme in the process of heme synthesis. This study aimed to investigate the association between ALAS1 gene polymorphism, serum ALAS1 level, and the risk of ATLI.

Association of DNA methylation, polymorphism and mRNA level of ALAS1 with antituberculosis drug-induced liver injury.

To investigate the association of DNA methylation, genetic polymorphisms and mRNA level of aminolevulinate synthase 1 (ALAS1) with antituberculosis drug-induced liver injury (AT-DILI) risk. Based on a 1:1 matched case-control study with 182 cases and 182 controls, one CpG island and three single nucleotide polymorphisms (SNPs) were detected. mRNA level was detected in 34 samples.

Relationship between common telomere length-related genetic variations, telomere length, and risk of antituberculosis drug-induced hepatotoxicity in Chinese Han population: As assessed for causality using the updated Roussel Uclaf Causality Assessment Method.

Antituberculosis drug-induced hepatotoxicity (ATDH) is a significant threat to tuberculosis control, and two recent studies indicated that leukocyte telomere length (LTL) might be a potential biomarker for ATDH. This study aimed to investigate the relationship between common telomere length-related genetic variations, LTL, and risk of ATDH in Eastern Chinese antituberculosis treatment patients. A 1:4 matched case-control study was conducted among 79 ATDH cases assessed for causality using the updated RUCAM and 316 controls.

The relationship between relative telomere length and anti-tuberculosis drug-induced hepatitis : A case-control study.

Aim: Anti-tuberculosis drug-induced hepatitis (AT-DIH) is a common and serious adverse drug reaction of tuberculosis treatment. Evidence demonstrated that many factors could affect the occurrence of AT-DIH, such as ageing, smoking, alcohol, oxidative stress, etc., while these factors could also promote telomere shortening.

Heme oxygenase-1 and hemopexin gene polymorphisms and the risk of anti-tuberculosis drug-induced hepatotoxicity in China.

To assess whether the risk of anti-tuberculosis drug-induced hepatotoxicity (ATDH) might be influenced by heme oxygenase-1 () and hemopexin () gene polymorphisms. A dynamic anti-tuberculosis treatment cohort was constructed, and the 1:4 matched nested case-control study was analysed. Eight single-nucleotide polymorphisms (SNPs) of the two genes were selected for genotyping and Bonferroni correction was performed to correct for multiple comparison.

The role of the genetic variant FECH rs11660001 in the occurrence of anti-tuberculosis drug-induced liver injury.

What Is Known And Objective: The pathogenic mechanism of anti-tuberculosis drug-induced liver injury (AT-DILI) is still largely unknown. Recent studies have indicated that rifampicin and isoniazid cotreatment causes the accumulation of endogenous protoporphyrin IX in the liver through the haem biosynthesis pathway. Alanine synthase 1 (ALAS1) and ferrochelatase (FECH) are the rate-limiting enzymes in the production of haem.

A validation study of the UGT1A4 rs2011404 variant and the risk of anti-tuberculosis drug-induced hepatotoxicity in an Eastern Chinese Han population.

What Is Known And Objective: Anti-tuberculosis (anti-TB) drug-induced hepatotoxicity (ATDH) is a serious adverse drug reaction. A recent study found that the rs2011404 variant of uridine 5'-diphospho-glucuronosyl-transferase 1A4 (UGT1A4) is a marker of susceptibility to ATDH. The present study aimed to validate this relationship in an Eastern Chinese Han anti-TB treatment population.

Association between NR1I2 polymorphisms and susceptibility to anti-tuberculosis drug-induced hepatotoxicity in an Eastern Chinese Han population: A case-control study.

Objective: Anti-tuberculosis drug-induced hepatotoxicity (ATDH) is a serious adverse drug reaction, and its pathogenic mechanism is still largely unknown. Pregnane X receptor (PXR, encoded by the NR1I2 gene) is a ligand-dependent transcription factor, and rifampicin is a human PXR-specific activator. Rifampicin and isoniazid co-therapy targets porphyrin biosynthesis via PXR and results in hepatic protoporphyrin IX accumulation and subsequent liver injury.

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

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.

Relevance of NAT2 genotype to anti-tuberculosis drug-induced hepatotoxicity in a Chinese Han population.

Background: 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.

Home-based Anti-Tuberculosis Treatment Adverse Reactions (HATTAR) study: a protocol for a prospective observational study.

Introduction: 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.

The A/A Genotype of XPO1 rs4430924 Is Associated With Higher Risk of Antituberculosis Drug-Induced Hepatotoxicity in Chinese Patients.

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.

Possible association of HMOX1 and NQO1 polymorphisms with anti-tuberculosis drug-induced liver injury: A matched case-control study.

What Is Known And Objective: Reactive metabolites from anti-tuberculosis (anti-TB) drugs can result in abnormal accumulation of reactive oxygen species (ROS), which plays an important role in anti-TB drug-induced liver injury (ATLI). Liver cells could keep the production of ROS in balance by antioxidant activities. The heme oxygenase 1, encoded by the HMOX1 gene and NADH:quinone oxidoreductase 1, encoded by the NQO1 gene are crucial mediators of cellular defense against ROS.

Association of FAM65B, AGBL4, and CUX2 genetic polymorphisms with susceptibility to antituberculosis drug-induced hepatotoxicity: validation study in a Chinese Han population.

Objective: Antituberculosis (anti-TB) drug-induced hepatotoxicity (ATDH) is a serious adverse drug reaction, and its pathogenic mechanism has not been elucidated thoroughly to date. A recent genome-wide association study reported that seven single-nucleotide polymorphisms (SNPs) in the family with sequence similarity 65, member B gene (FAM65B), ATP/GTP-binding protein-like 4 gene (AGBL4), and cut-like homeobox 2 gene (CUX2) were associated strongly with ATDH in Ethiopian patients. We validated this relationship in a Chinese Han anti-TB treatment population.