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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

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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)

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.

Suggested Citation

  • Jinling Zhang & Xuebin Zhu & Yuhong Li & Lingyan Zhu & Shiming Li & Guoying Zheng & Qi Ren & Yonghong Xiao & Fumin Feng, 2016. "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," IJERPH, MDPI, vol. 13(8), pages 1-9, August.
    • Handle: RePEc:gam:jijerp:v:13:y:2016:i:8:p:776-:d:75162
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    References listed on IDEAS

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    1. Alexander Meissner & Tarjei S. Mikkelsen & Hongcang Gu & Marius Wernig & Jacob Hanna & Andrey Sivachenko & Xiaolan Zhang & Bradley E. Bernstein & Chad Nusbaum & David B. Jaffe & Andreas Gnirke & Rudol, 2008. "Genome-scale DNA methylation maps of pluripotent and differentiated cells," Nature, Nature, vol. 454(7205), pages 766-770, August.
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