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Background  Anti-tuberculosis (anti-TB) drug-induced liver injury (ADLI) is one of the most common adverse effects associated with TB treatment. Cytochrome P450 (CYP) 1A1 and glutathione S-transferase (GST) P1 are important phase I/II metabolizing enzymes involved in drug metabolism and detoxification. Genetic polymorphism and CpG island methylation have been reported as factors influencing the expression of  CYP1A1  and  GSTP1 .    Objective  This study aimed to determine the potential relationships of  CYP1A1  and  GSTP1  polymorphisms and CpG island methylation with ADLI risk.    Design  This was a population-based one-to-one matched case–control study.    Setting  The subjects were patients with TB receiving treatment in China from December 2010 to June 2013.    Patients  In total, 127 patients with TB and ADLI (case group) and 127 patients with TB but without liver injury (control group) were included in this study. Subjects were matched in terms of sex, age, and therapeutic regimen.    Methods  The general condition of each patient was assessed using questionnaires. The  CYP1A1  MspI and  GSTP1  Ile105Val polymorphisms as well as methylation status were detected by polymerase chain reaction (PCR)–restriction fragment length polymorphism and the methylation-specific PCR method.    Results  We found no significant difference in  GSTP1  and  CYP1A1  genotypes between the two groups, probably because the sample size was not large enough; however, patients with ADLI had significantly higher  GSTP1  and  CYP1A1  promoter methylation rates than control subjects [odds ratio (OR) = 2.467 and 2.000, respectively]. After adjusting for drinking, which significantly differed between the groups as per univariate analysis, we found that hypermethylation of  GSTP1  and  CYP1A1  promoters was associated with ADLI (OR = 2.645 and 2.090, respectively).    Conclusion  Hypermethylation of CpG islands of  GSTP1  and  CYP1A1  promoters may thus play important roles in the development of ADLI and provide evidence of being used as novel markers for ADLI risk prediction.

plos one

Involvement of Cytochrome P450 1A1 and Glutathione S-Transferase P1 Polymorphisms and Promoter Hypermethylation in the Progression of Anti-Tuberculosis Drug-Induced Liver Injury: A Case–Control Study