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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., (© 2021. The Author(s).)

This study investigated the diagnostic value of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) contents of human leucocyte antigen (HLA)-B and HLA-DQB1 in anti-tuberculosis drug-induced liver injury (ADLI). In total, 110 ADLI patients and 120 patients without ADLI controls were enrolled. Enzyme-linked immunosorbent assay (ELISA) was used to detect the 5-mC and 5-hmC content in DNA from peripheral blood leucocytes. The univariate analysis showed that smoking, drinking, and 5-mC and 5-hmC content of HLA-B and HLA-DQB1 were significantly associated with ADLI. After adjusting for drinking and smoking, we found that 5-mC content of HLA-B and HLA-DQB1 were associated with ADLI (odds ratio [OR] = 0.251 and 0.347, respectively) and 5-hmC contents of HLA-B and HLA-DQB1 were also associated with ADLI (OR = 1.848 and 4.705, respectively). Receiver operating characteristic (ROC) analysis indicated that the 5-hmC contents of both HLA-B and HLA-DQB1 were more clinically significant than the 5-mC contents were. The combined 5-hmC level of HLA-B and HLA-DQB1 was the best diagnostic biomarker for ADLI, with the highest areas under the curve (AUC) for 0.953, sensitivity for 0.900 and specificity for 0.875. Therefore, combined 5-hmC levels of HLA-B and HLA-DQB1 could be significant evidence for diagnosis of ADLI., (© 2020 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.)