TANC1 methylation as a novel biomarker for the diagnosis of patients with anti-tuberculosis drug-induced liver injury

Abstract

We aimed to elucidate the differences in genomic methylation patterns between ADLI and non-ADLI patients to identify DNA methylation-based biomarkers. Genome-wide DNA methylation patterns were obtained using Infinium MethylationEPIC (EPIC) BeadChip array to analyze 14 peripheral blood samples (7 ADLI cases, 7 non-ADLI controls). Changes in the mRNA and DNA methylation in the target genes of another 120 peripheral blood samples (60 ADLI cases, 60 non-ADLI controls) were analyzed by real-time polymerase chain reaction and pyrosequencing, respectively. A total of 308 hypermethylated CpG sites and 498 hypomethylated CpG sites were identified. Significantly, hypermethylated CpG sites cg06961147 and cg24666046 in TANC1 associated with ADLI was identified by genome-wide DNA methylation profiling. The mRNA expression of TANC1 was lower in the cases compared to the controls. Pyrosequencing validated these two differentially methylated loci, which was consistent with the results from the EPIC BeadChip array. Receiver operating characteristic analysis indicated that the area under the curve of TANC1 (cg06961147, cg24666046, and their combinations) was 0.812, 0.842, and 0.857, respectively. These results indicate that patients with ADLI have different genomic methylation patterns than patients without ADLI. The hypermethylated differentially methylated site cg06961147 combined with cg24666046 in TANC1 provides evidence for the diagnosis of ADLI.

Association of a Novel DOCK2 Mutation-Related Gene Signature With Immune in Hepatocellular Carcinoma

“…TANC1 has an ankyrin repeat (AR) domain that participates in many cell functions, especially tumorigenesis ( Yang et al, 2019 ). Through Ingenuity Pathway Analysis (IPA), genes regulated by TANC1 were enriched in hepatic inflammation and HCC ( Wu et al, 2021 ). ALKBH7, a mitochondrial ketoglutarate dioxygenase, decreases ROS formation to regulate programmed necrosis ( Meng et al, 2019 ; Kulkarni et al, 2020 ).…”

Interaction between the HIF‐1α gene rs1957757 polymorphism and CpG island methylation in the promoter region is associated with the risk of anti‐tuberculosis drug‐induced liver injury in humans: A case–control study

“…The inclusion criteria for the case group included liver injury after 2 months of treatment with anti‐TB drugs. The inclusion criteria for the control group included the absence of liver injury after 2 months of anti‐TB drug treatment and a match with patients in the case group in terms of age (<5 years difference), sex and therapeutic regimen (daily S(E)HRZ: S, streptomycin; E, ethambutol; H, isoniazid, R, rifampicin; Z, pyrazinamide) 16,17 …”

“…Hepatotoxicity due to anti‐TB drug treatment was not only based on the liver enzyme results, according to the criteria of the American Thoracic Society (ATS), but also took into account the diagnostic criteria developed by the Center for Drug Re‐evaluation (CDR) of the Chinese State Food and Drug Administration, as well as various previous definitions. Specifically, ADLI patients need to meet one of the following criteria 17 : (1) an increase in serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST), which is over threefold the upper limit of normal (ULN) in the presence of liver injury symptoms; (2) an increase in total bilirubin (TBIL) that is over twofold the ULN in the presence of liver injury symptoms; (3) a fivefold increase in the ULN of serum ALT, AST or TBIL with or without liver injury symptoms.…”

“…The inclusion criteria for the control group included the absence of liver injury after 2 months of anti-TB drug treatment and a match with patients in the case group in terms of age (<5 years difference), sex and therapeutic regimen (daily S(E) HRZ: S, streptomycin; E, ethambutol; H, isoniazid, R, rifampicin; Z, pyrazinamide). 16,17 Hepatotoxicity due to anti-TB drug treatment was not only based on the liver enzyme results, according to the criteria of the American Thoracic Society (ATS), but also took into account the diagnostic criteria developed by the Center for Drug Re-evaluation (CDR) of the Chinese State Food and Drug Administration, as well as various previous definitions. Specifically, ADLI patients need to meet one of the following criteria 17 : (1) an increase in serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST), which is over…”

Relationship between DNA Methylation Profiles and Active Tuberculosis Development from Latent Infection: a Pilot Study in Nested Case-Control Design

“…Since epigenetics can bridge the gaps between the host, M. tuberculosis , and the environment, it might have great potential in predicting TB development. DNA methylation is the most widely studied epigenetic marker, and cytosine-guanine dinucleotide (CpG) methylation is central to many biological processes and human diseases ( 11 – 14 ). Previous studies reported that varied DNA methylation might be associated with TB risk ( 15 , 16 ).…”