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Genome‐Wide Analysis of DNA Methylation and Antituberculosis Drug‐Induced Liver Injury in the Han Chinese Population

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 MassARRAY 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 AK2, SLC8A2, and PSTPIP2 affected the cellular response to rifampicin treatment. This study provides new biomarkers associated with ATLI occurrence.