DNA methylation microarray-based screening of epigenetically masked genes in patients with anti-tuberculosis drug-induced liver injury

• Main Authors: LI Yuhong, JIAO Lianli, HAO Mingyuan
• Format: Article
• Language: zho
• Published: Editorial Office of Journal of Third Military Medical University 2019-02-01
• Series: Di-san junyi daxue xuebao
• Subjects: anti-tuberculosis drug-induced liver injury; dna methylation; microarray
• Online Access: http://aammt.tmmu.edu.cn/Upload/rhtml/201810029.htm

Objective To investigate the differentially methylated genes between patients with anti-tuberculosis drug induced liver injury (ADLI) and patients without hepatic injury using DNA methylation microarrays and explore the relationship between DNA methylation and ADLI. Methods This study was conducted among 137 patients with newly diagnosed pulmonary tuberculosis (including 65 patients with ADLI and 72 without ADLI) treated in the Fourth Hospital of Tangshan City between January, 2016 and July, 2017. The clinical data were collected and whole blood samples were obtained from all the patients, and 14 patients, including 7 with ADLI and 7 without ADLI, were selected for examination of DNA methylation status using Illumina 850K bead-chip. The methylation status of the 2 differentially methylated genes, DUSP22 and HLA-C, which were identified by analysis of the microarray data, were verified in the remaining cases using methylation-specific PCR (MSP); RT-PCR was used to detect the mRNA levels of DUSP22 and HLA-C genes in all the patients. Results We analyzed a total of 853 307 loci and identified 1 012 differential methylated loci between ADLI group and non-ADLI group, including 254 hypermethylated and 758 hypomethylated loci, located mainly in the gene body regions. Cluster analysis showed that a large number of differentially methylated genes were involved in the process of cell adhesion and metal ion binding. MSP verified that the methylation rates of DUSP22 and HLA-C genes differed significantly between ADLI group and non-ADLI group (65.6% vs 36.9%; 37.9% vs 58.5%; both P < 0.05). The mRNA expression of DUSP22 was higher and that of HLA-C was lower in non-ADLI group than in ADLI group. Conclusion DNA methylation of DUSP22 and HLA-C in the peripheral blood is associated with the development of ADLI.