Genetic Variations in TXNRD1 as Potential Predictors of Drug-Induced Liver Injury.
10.4168/aair.2012.4.3.132
- Author:
Jae Woo KWON
1
;
Eun Soon SHIN
;
Jong Eun LEE
;
Sang Heon KIM
;
Sang Hoon KIM
;
Young Koo JEE
;
Yoon Keun KIM
;
Hae Sim PARK
;
Kyung Up MIN
;
Heung Woo PARK
Author Information
1. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. guinea71@snu.ac.kr
- Publication Type:Original Article
- Keywords:
Drug-induced liver injury;
genetic association study;
genetic polymorphism;
single nucleotide polymorphisms;
thioredoxin reductase 1
- MeSH:
Alleles;
Animals;
Anti-Bacterial Agents;
Anticonvulsants;
Drug Toxicity;
Drug-Induced Liver Injury;
Genetic Association Studies;
Genetic Variation;
Haplotypes;
Humans;
Liver;
Polymorphism, Genetic;
Polymorphism, Single Nucleotide;
Republic of Korea;
Thioredoxin Reductase 1
- From:Allergy, Asthma & Immunology Research
2012;4(3):132-136
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: 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.
