title: Polymorphism of PXR gene associated with the increased risk of drug-induced liver injury in Indonesian pulmonary tuberculosis patients.
abstract: OBJECTIVE
  Tuberculosis is still a major infectious disease in Indonesia. Patients are treated mostly using fixed-dose combination treatment in primary public health facilities. The incidence of antituberculosis drug-induced liver injury (AT-DILI) is approximately 10% among Indonesian tuberculosis patients who used standard fixed combination regimens during the intensive phase of treatment. However, information regarding genetic polymorphism associated with the increase risk of drug-induced liver injury is still limited. The aim of this study was to investigate pregnane X receptor (PXR) gene polymorphisms as one of the risk factors of AT-DILI.
  
  
  METHODS
  In this prospective cohort study, we recruited 106 adult patients diagnosed with pulmonary tuberculosis and treated with category I FDC (fixed-dose combination). The identification of SNP -25385C>T (rs3814055) was conducted by ARMS (amplification refractory mutation system). Hepatotoxicity was defined as ALT and/or AST levels above the normal threshold on the second, fourth and sixth months of monitoring during tuberculosis treatment.
  
  
  CONCLUSIONS
  The logistic regression analysis showed that patients with the TT genotype of PXR gene (rs3814055) significantly had a greater risk of AT-DILI (OR 8·89; 95% CI 1·36-57·93, P < 0·05), compared with those of wild-type CC genotype.
  
  
  CONCLUSIONS
  The result suggests that in Indonesian patients with tuberculosis, the risk of having AT-DILI was associated with TT genotype of the PXR gene.
authors.affiliation: Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, Indonesia.
authors.forename: Z
authors.initials: Z
authors.lastname: Zazuli
authors.affiliation: Department of Biological Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, Indonesia.
authors.forename: M I
authors.initials: MI
authors.lastname: Barliana
authors.affiliation: Center for Applied Health Technology and Clinical Epidemiology, National Institute of Health Research and Development, Ministry of Health Republic of Indonesia, Jakarta, Indonesia.
authors.forename: U A
authors.initials: UA
authors.lastname: Mulyani
authors.affiliation: Faculty of Pharmacy, Universitas Ahmad Dahlan, Yogyakarta, Indonesia.
authors.forename: D A
authors.initials: DA
authors.lastname: Perwitasari
authors.affiliation: Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, Indonesia.
authors.forename: H
authors.initials: H
authors.lastname: Ng
authors.affiliation: Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, Indonesia.
authors.forename: R
authors.identifier: http://orcid.org/0000-0002-8779-6421
authors.initials: R
authors.lastname: Abdulah
mesh_terms: D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000009:adverse effects* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007214:Indonesia; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000077297:Pregnane X Receptor; D011446:Prospective Studies; D011987:Receptors, Steroid / Q000235:genetics* / Q000627:therapeutic use; D012307:Risk Factors; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000235:genetics*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid
keywords: PXR; antituberculosis drugs; drug-induced hepatotoxicity; drug-induced liver injury; polymorphism