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Int. J. Environ. Res. Public Health 2016, 13(8), 776; doi:10.3390/ijerph13080776

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

1
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
2
Department of Clinical Laboratories, Tangshan Tuberculosis Hospital, Tangshan 063000, China
*
Author to whom correspondence should be addressed.
Academic Editor: Paul B. Tchounwou
Received: 4 June 2016 / Revised: 18 July 2016 / Accepted: 27 July 2016 / Published: 1 August 2016
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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. View Full-Text
Keywords: tuberculosis; anti-TB drug-induced liver injury; methylation; cytochrome P450 2E1; cytochrome P450 2D6; case-control study tuberculosis; anti-TB drug-induced liver injury; methylation; cytochrome P450 2E1; cytochrome P450 2D6; case-control study
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Zhang, J.; Zhu, X.; Li, Y.; Zhu, L.; Li, S.; Zheng, G.; Ren, Q.; Xiao, Y.; Feng, F. 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. Int. J. Environ. Res. Public Health 2016, 13, 776.

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