title: Correlation of CpG Island Methylation of the Cytochrome P450 2E1/2D6 Genes with Liver Injury Induced by Anti-Tuberculosis Drugs: A Nested Case-Control Study.
abstract: This study investigated the role of CpG island methylation of the CYP2E1 and CYP2D6 genes in liver injury induced by anti-TB drugs from an epigenetic perspective in a Chinese cohort. A 1:1 matched nested case-control study design was applied. Pulmonary tuberculosis (TB) patients, who underwent standard anti-TB therapy and developed liver injury were defined as cases, while those who did not develop liver injury were defined as control. The two groups were matched in terms of sex, treatment regimen, and age. In 114 pairs of cases, CpG island methylation levels of the CYP2E1 and CYP2D6 genes in plasma cell-free DNA were found to be significantly correlated with the occurrence of anti-TB drug-induced liver injury (ADLI), with odds ratio (OR) values of 2.429 and 3.500, respectively (p < 0.01). Moreover, through multivariate logistic regression analysis, CpG island methylation of the CYP2E1 and CYP2D6 genes in plasma cell-free DNA were found to be significantly correlated with the occurrence of ADLI, with adjusted OR values of 4.390 (95% confidence interval (CI): 1.982-9.724) and 9.193 (95% CI: 3.624-25.888), respectively (p < 0.001). These results suggest that aberrantly elevated methylation of CpG islands of the CYP2E1 and CYP2D6 genes in plasma cell-free DNA may increase the risk of ADLI in Chinese TB patients.
authors.affiliation: Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, School of Public Health, North China University of Science and Technology, No.57 Jianshe Road, Tangshan 063000, China. xiaoyao_1986@126.com.
authors.forename: Jinling
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, School of Public Health, North China University of Science and Technology, No.57 Jianshe Road, Tangshan 063000, China. zxb5060408412@sina.com.
authors.forename: Xuebin
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, School of Public Health, North China University of Science and Technology, No.57 Jianshe Road, Tangshan 063000, China. 15133912746@163.com.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, School of Public Health, North China University of Science and Technology, No.57 Jianshe Road, Tangshan 063000, China. erheyan@163.com.
authors.forename: Lingyan
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Clinical Laboratories, Tangshan Tuberculosis Hospital, Tangshan 063000, China. lsm2268909good@163.com.
authors.forename: Shiming
authors.initials: S
authors.lastname: Li
authors.affiliation: Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, School of Public Health, North China University of Science and Technology, No.57 Jianshe Road, Tangshan 063000, China. zhengying0918@aliyun.com.
authors.forename: Guoying
authors.initials: G
authors.lastname: Zheng
authors.affiliation: Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, School of Public Health, North China University of Science and Technology, No.57 Jianshe Road, Tangshan 063000, China. qren0819@hotmail.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Ren
authors.affiliation: Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, School of Public Health, North China University of Science and Technology, No.57 Jianshe Road, Tangshan 063000, China. kycxyh@tom.com.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, School of Public Health, North China University of Science and Technology, No.57 Jianshe Road, Tangshan 063000, China. fm_feng@sina.com.
authors.forename: Fumin
authors.initials: F
authors.lastname: Feng
mesh_terms: D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000009:adverse effects*; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics*; D018899:CpG Islands; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008745:Methylation; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012306:Risk; D014376:Tuberculosis / Q000188:drug therapy; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D019392:Cytochrome P-450 CYP2E1; D019389:Cytochrome P-450 CYP2D6
keywords: anti-TB drug-induced liver injury; case-control study; cytochrome P450 2D6; cytochrome P450 2E1; methylation; tuberculosis