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

Jinling Zhang, Xuebin Zhu, Yuhong Li, Lingyan Zhu, Shiming Li, Guoying Zheng, Qi Ren, Yonghong Xiao and Fumin Feng
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Jinling Zhang: 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
Xuebin Zhu: 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
Yuhong Li: 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
Lingyan Zhu: 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
Shiming Li: Department of Clinical Laboratories, Tangshan Tuberculosis Hospital, Tangshan 063000, China
Guoying Zheng: 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
Qi Ren: 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
Yonghong Xiao: 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
Fumin Feng: 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

IJERPH, 2016, vol. 13, issue 8, 1-9

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.

Keywords: tuberculosis; anti-TB drug-induced liver injury; methylation; cytochrome P450 2E1; cytochrome P450 2D6; case-control study (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2016
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