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Genome‐Wide Analysis of DNA Methylation and Antituberculosis Drug‐Induced Liver Injury in the Han Chinese Population
Author(s) -
Huai Cong,
Wei Yuqi,
Li Mo,
Zhang Xiaoqing,
Wu Hao,
Qiu Xiaoyan,
Shen Lu,
Chen Luan,
Zhou Wei,
Zhang Na,
Zhu Guanghui,
Zhang Ying,
Zhang Zhiruo,
He Lin,
Qin Shengying
Publication year - 2019
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.1563
Subject(s) - dna methylation , liver injury , cpg site , gene , single nucleotide polymorphism , methylation , biology , population , genome , tuberculosis , drug , rifampicin , medicine , pharmacology , genetics , gene expression , genotype , pathology , environmental health
Tuberculosis ( TB ) is one of the most prevalent infections. However, anti‐ TB drugs induce adverse liver injury in up to 40% of patients. Studies on candidate genes have suggested that single‐nucleotide polymorphisms account for only a small contribution to the occurrence of anti‐TB drug‐induced liver injury ( ATLI ). In this study, whole‐genome DNA methylation analysis was performed to systematically screen the ATLI ‐associated factors in a 49 vs. 51 case‐control population. Next, 34 identified candidate probes were validated using Mass ARRAY in 296 cases and 288 controls. Our results indicated that 12 CpG sites on seven probes were positively associated with ATLI risk. Furthermore, we applied a CRISPR /Cas9‐mediated methylation modifiable cell model and demonstrated that four CpGs in or near the gene region of AK 2 , SLC 8A2 , and PSTPIP 2 affected the cellular response to rifampicin treatment. This study provides new biomarkers associated with ATLI occurrence.