title: 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.
abstract: 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.
  
  
  METHODS
  This was a population-based one-to-one matched case-control study.
  
  
  METHODS
  The subjects were patients with TB receiving treatment in China from December 2010 to June 2013.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors: Key Laboratory of Occupational Health and Safety, School of Public Health, Hebei United University, Tangshan 063000, China.
authors: Lei
authors: L
authors: He
authors: Key Laboratory of Occupational Health and Safety, School of Public Health, Hebei United University, Tangshan 063000, China.
authors: Li
authors: L
authors: Gao
authors: Key Laboratory of Occupational Health and Safety, School of Public Health, Hebei United University, Tangshan 063000, China.
authors: Zhe
authors: Z
authors: Shi
authors: Key Laboratory of Occupational Health and Safety, School of Public Health, Hebei United University, Tangshan 063000, China.
authors: Yuhong
authors: Y
authors: Li
authors: Key Laboratory of Occupational Health and Safety, School of Public Health, Hebei United University, Tangshan 063000, China.
authors: Lingyan
authors: L
authors: Zhu
authors: Department of Clinical Laboratories, Tangshan Tuberculosis Hospital, Tangshan 063000, China.
authors: Shiming
authors: S
authors: Li
authors: Department of Clinical Laboratories, Tangshan Tuberculosis Hospital, Tangshan 063000, China.
authors: Peng
authors: P
authors: Zhang
authors: Key Laboratory of Occupational Health and Safety, School of Public Health, Hebei United University, Tangshan 063000, China.
authors: Guoying
authors: G
authors: Zheng
authors: Key Laboratory of Occupational Health and Safety, School of Public Health, Hebei United University, Tangshan 063000, China.
authors: Qi
authors: Q
authors: Ren
authors: Key Laboratory of Occupational Health and Safety, School of Public Health, Hebei United University, Tangshan 063000, China.
authors: Yun
authors: Y
authors: Li
authors: Key Laboratory of Occupational Health and Safety, School of Public Health, Hebei United University, Tangshan 063000, China.
authors: Bo
authors: B
authors: Hu
authors: Key Laboratory of Occupational Health and Safety, School of Public Health, Hebei United University, Tangshan 063000, China.
authors: Fumin
authors: F
authors: Feng
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D002681:China / Q000453:epidemiology; D018899:CpG Islands / Q000235:genetics; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D019175:DNA Methylation; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014376:Tuberculosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi