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Combined 5‐hydroxymethylcytosine content of human leucocyte antigen‐B and human leucocyte antigen‐DQB1 as novel biomarker for anti‐tuberculosis drug‐induced liver injury
Authors:Yuhong Li  Qi Ren  Dongxue Wu  Mi Zhang  Xue Wang  Hanyu Zhu  Shufeng Sun  Fumin Feng
Abstract: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.
Keywords:5‐methylcytosine  5‐hydroxymethylcytosine  anti‐tuberculosis drug‐induced liver injury  biomarker  peripheral blood leucocytes
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