Anti-tuberculosis drug-induced liver injury correlated with the methylation in the promoter regions of CYP2E1 and GSTM1 / 医学研究生学报

ABSTRACT

Objective No study has been reported on the association between the abnormal methylation of drug metabolic enzymes and anti-tuberculosis drug-induced liver injury (ATLI). This article aimed to investigate the relationship of ATLI with the methylation of the CpG islands in the promoter regions of cytochrome P450 2E1 (CYP2E1) and glutathione s-transferase M1 (GSTM1) in Chinese Mongolian patients with tuberculosis (TB). Methods This retrospective study included 93 cases of TB diagnosed and treated in the TB prevention and treatment institutions of Tongliao, Inner Mongolia, between September 2016 and December 2017, which were divided into an ATLI (n = 31) and a non-ATLI group (n = 62), the former with and the latter without ATLI within 6 months after anti-TB medication. We compared the methylation levels of the CYP2E1 and GSTM1 genes between the two groups of patients and analyzed the risk factors of ATLI. Results In comparison with the non-ATLI controls, the patients of the ATLI group showed significantly lower methylation levels in the promoter regions of CYP2E1 (0.759 ± 0.066 vs 0.694 ± 0.091, P < 0.05) and GSTM1 (0.207 ± 0.093 vs 0.187 ± 0.092, P < 0.05). Multivariate logistic regression analysis revealed that the main risk factors of ATLI included alcohol consumption (OR = 5.329, 95% CI 1.442-19.697, P < 0.05) and methylation in the CYP2E1 promoter region (OR = 0.312, 95% CI 0.165-0.591, P < 0.05) in the TB patients. Conclusion ATLI is associated with the methylation level in the promoter region of the CYP2E1 gene in Chinese Mongolian patients with tuberculosis, indicating that the methylation of CYP2E1 could be used as a biomarker in the prevention and control of ATLI.