title: Genetic Variations in TXNRD1 as Potential Predictors of Drug-Induced Liver Injury.
abstract: OBJECTIVE
  Drug-induced liver injury (DILI) is the most common adverse drug reaction; however, it is not easily predicted. We hypothesize that DILI has a common genetic basis. Based on the findings of previous animal studies on toxic hepatitis, we selected the thioredoxin reductase 1 gene (TXNRD1) as a candidate marker of DILI for this genetic association study.
  
  
  METHODS
  Records from 118 patients with DILI were extracted from the database of the Adverse Drug Reaction Research Group in South Korea. Causative drugs included antituberculosis drugs (n=68, 57.6%), antibiotics (n=22, 18.6%), antiepileptic drugs (n=7, 5.9%), non-steroidal anti-inflammatory drugs (n=5, 4.2%), and others (n=16, 13.7%). Seven single nucleotide polymorphisms (SNPs) in TXNRD1 (rs10735393, rs4964287, rs4595619, rs10861201, rs11111997, rs4246270, and rs4246271) were scored in 118 DILI patients and in 120 drug-matched controls without liver injury.
  
  
  RESULTS
  No differences were found between the frequencies of any of the 7 SNPs in the cases and controls; however, a significant association was found between a TTA haplotype composed of rs10735393, rs4964287, and rs4595619 and DILI using an allele model (odds ratio, 1.79; 95% confidence interval, 1.18-2.73; P=0.008; Bonferroni corrected P=0.024).
  
  
  CONCLUSIONS
  These results suggest that genetic variations in TXNRD1 favor the development of DILI, although a larger confirmative study is needed.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jae-Woo
authors.initials: JW
authors.lastname: Kwon
authors.forename: Eun-Soon
authors.initials: ES
authors.lastname: Shin
authors.forename: Jong-Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Sang-Heon
authors.initials: SH
authors.lastname: Kim
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Young-Koo
authors.initials: YK
authors.lastname: Jee
authors.forename: Yoon-Keun
authors.initials: YK
authors.lastname: Kim
authors.forename: Hae-Sim
authors.initials: HS
authors.lastname: Park
authors.forename: Kyung-Up
authors.initials: KU
authors.lastname: Min
authors.forename: Heung-Woo
authors.initials: HW
authors.lastname: Park