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.
Highlights
With an incidence rate ranging between 5% and 33% [1,2], anti-TB drug-induced liver injury (ADLI) is the main cause of failure or interruption of anti-TB therapy [3]
A total of 1291 patients finished a six-month follow-up, 21 cases were lost, 164 cases met the diagnostic criteria of ADLI, 114 cases were selected by the treatment time, and 114 cases without liver injury were selected as controls
The results showed that the occurrence of CpG island hypermethylation of the CYP2E1 and CYP2D6 genes was significantly different between the case and the control groups
Summary
With an incidence rate ranging between 5% and 33% [1,2], anti-TB drug-induced liver injury (ADLI) is the main cause of failure or interruption of anti-TB therapy [3]. Anti-TB drugs are metabolized in the liver by phase I and phase II metabolizing enzymes [4,5]. The activities of these enzymes can be influenced by gene polymorphism, which may result in decreased detoxification ability of the liver. Various forms of these enzymes, such as slow acetylation genotype of N-acetyltransferase 2, wild genotype of cytochrome P450 (CYP) 2E1, and gene deletion type of glutathione S-transferase M1, have been found to comprise high-risk genotypes for ADLI [6,7,8]. Public Health 2016, 13, 776; doi:10.3390/ijerph13080776 www.mdpi.com/journal/ijerph
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