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Allergy Asthma Immunol Res. 2012 May;4(3):132-6. doi: 10.4168/aair.2012.4.3.132. Epub 2011 Nov 10.

Genetic Variations in TXNRD1 as Potential Predictors of Drug-Induced Liver Injury.

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  • 1Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

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.

KEYWORDS:

Drug-induced liver injury; genetic association study; genetic polymorphism; single nucleotide polymorphisms; thioredoxin reductase 1

PMID:
22548205
[PubMed]
PMCID:
PMC3328729
Free PMC Article

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