Global DNA hypomethylation of Alu and LINE-1 transposable elements as an epigenetic biomarker of anti-tuberculosis drug-induced liver injury

Emerging Microbes and Infections

卷:10

Wasun Chantratita¹  Jiraphun Jittikoon²  Wanvisa Udomsinprasert²  Sittisak Honsawek³  Sukanya Wattanapokayakit⁴  Surakameth Mahasirimongkol⁴  Wanchaloem Sakuntasri⁵  Usa Chaikledkaew⁶ 

[1] Center for Medical Genomics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand;

[2] Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand;

[3] Department of Biochemistry, Osteoarthritis and Musculoskeleton Research Unit, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand;

[4] Division of Genomic Medicine and Innovation Support, Department of Medical Sciences, Ministry of Public Health, Genomic Medicine Centre, Nonthaburi, Thailand;

[5] Master of Science Program in Biopharmaceutical Sciences, Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand;

[6] Social and Administrative Pharmacy Division, Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand;

关键词: Alu;    LINE-1;    global DNA methylation;    anti-tuberculosis drug-induced liver injury;    tuberculosis;    biomarker;   

DOI  :  10.1080/22221751.2021.1976079

来源: DOAJ

【 摘 要 】

Despite being highly effective, anti-tuberculosis (TB) drugs often induce adverse liver injury, anti-TB drug-induced liver injury (ATDILI), leading to treatment failure given no sensitive and selective ATDILI markers. Herein, we conducted a case–control association study to determine whether global DNA methylation of Alu and LINE-1 transposable elements responsible for genomic stability and transcriptional regulation was correlated with clinical parameters indicating ATDILI in TB patients and might serve as an ATDILI biomarker. Alu and LINE-1 methylation levels in blood leukocyte of 130 TB patients (80 ATDILI cases and 50 non-ATDILI cases) and 100 healthy controls were quantified using quantitative combined bisulfite restriction analysis. Both TB patients with and without ATDILI had significantly lower methylation levels of Alu and LINE-1 elements than healthy controls. Compared with non-ATDILI patients, Alu methylation levels were significantly decreased in ATDILI patients, commensurate with LINE-1 methylation analysis. Hypomethylation of Alu and LINE-1 measured within 1–7 days of TB treatment was independently associated with raised levels of serum aminotransferases assessed within 8–60 days of TB treatment. Receiver operating characteristic curve analysis uncovered that Alu and LINE-1 methylation levels were both more sensitive and specific for differentiating ATDILI cases from non-ATDILI cases than serum aminotransferases after starting TB treatment within 1–7 days. Kaplan-Meier analysis displayed a significant association between hypomethylation of Alu and LINE-1 elements and an increased rate of ATDILI occurrence in TB patients. Collectively, global DNA hypomethylation of Alu and LINE-1 elements would reflect ATDILI progression and might serve as novel sensitive and specific ATDILI biomarkers.

【 授权许可】

Unknown