Paper Title
Screening for Epigenetically Masked Genes in Anttuberculosis Drug-Induced Liver Injury by Microarray

Abstract
We used the DNA methylation microarrays to investigate the differential methylation genes loci sites between patients with anti-tuberculosis drug induced liver injury (ADLI) and patients with non-hepatic injury, to study the relationship between DNA methylation and ADLI.Totally 137 patientswith newly diagnosed pulmonary tuberculosis treated in the Fourth Hospital of Tangshan City from January 2016 to July 2017 were enrolled in this study, including 65 with ADLI group, 72 with non-ADLI group. Clinical general data and whole blood specimens of the study subjects were collected. 14 patients (7 ADLI group, 7 non-ADLI group) were selected, DNA from whole blood samples was extracted, and methylation status in case group and control group were detected by Illumina 850K bead-chip. The differentially methylated genes DUSP22 and HLA-C were screened for the chip, and methylation-specific PCR (MSP) was used to verify methylation status in the remaining 65 cases and 58 controls. The mRNA levels of DUSP22 and HLA-C genes were detected by real-time PCR(RT-PCR).A total of 853,307 loci sites were analyzed and compared, 1012 differential methylated loci were found by comparing case group and control group, including 254 hypermethylated sites and 758 hypomethylated sites, which mainly located in the genebody region. The results of cluster analysis showed that there were a large number of differential methylation genes in the process of cell adhesion and metal ion binding. MSP method was used to verify that the methylation rates of homo sapiens dual specificity phosphatase 22 (DUSP22) and human leukocyte antigen (HLA-C) genes in the case group and the control group were (65.6% vs 36.9%) and (37.9% vs 58.5%), respectively, there were significant differences (P <0.05).The mRNA expression of DUSP22 in the control group was lower than that in the case group, and the mRNA expression of HLA-C was higher than that in the case group.The results suggested that DNA methylation of DUSP22 and HLA-C genes in peripheral blood was associated with the development of ADLI. Key words - Anti-tuberculosis druginduced liver injury; DNA methylation; Microarray