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Investigation of Oxidative Stress-Related Candidate Genes as Risk Factors for Drug-Induced Liver Injury due to Co-Amoxiclav

Lookup NU author(s): Mohammad Alshabeeb, Professor Ann DalyORCiD



This is the authors' accepted manuscript of an article that has been published in its final definitive form by Mary Ann Liebert, Inc. Publishers, 2020.

For re-use rights please refer to the publisher's terms and conditions.


The liver is susceptible to drug toxicity due to its vital role in xenobiotic metabolism and elimination. In addition to human leukocyte antigen (HLA) variants, which were previously determined as risk factors for drug-induced liver injury (DILI) due to co-amoxiclav, other non-HLA genes may contribute to hepatotoxicity risk. In this study, the association between DILI due to co-amoxiclav and several non-HLA genes was investigated. Association of variants in candidate genes (SOD2, GPX1, GSTM1, and GSTT1) with DILI due to various drugs was reported previously in other DILI cohorts. This study examined relevance in a co-amoxiclav-DILI cohort. One hundred sixty-five co-amoxiclav DILI cases were recruited from several European countries by two different studies (DILIGEN and iDILIC). A North-East England population group (n = 334) was used as the control group. PCR assays were used to genotype for the GSTM1 and GSTT1 null alleles with TaqMan SNP genotyping assays used for SOD2 (rs4880) and GPX1 (rs1050450). Fisher's exact test was used to assess differences in significance between cases and controls. None of the studied variants (SOD2 rs4880, GPX1 rs1050450, GSTM1 null allele, and GSTT1 null allele) was significantly associated with co-amoxiclav DILI compared with the control group. No significant differences between cases and controls were seen when combined SOD2/GPX1 genotypes and GST genotypes were considered. Despite the possible functional relevance and the previously reported contribution of the selected genes to DILI, our study failed to confirm associations between the selected genes and liver injury induced by co-amoxiclav.

Publication metadata

Author(s): Alshabeeb MA, Aithal GP, Daly AK

Publication type: Article

Publication status: Published

Journal: DNA and Cell Biology

Year: 2020

Volume: 39

Issue: 3

Pages: 349-354

Print publication date: 05/03/2020

Online publication date: 06/01/2020

Acceptance date: 26/11/2019

Date deposited: 02/07/2021

ISSN (print): 1044-5498

ISSN (electronic): 1557-7430

Publisher: Mary Ann Liebert, Inc. Publishers


DOI: 10.1089/dna.2019.4982

PubMed id: 31905014


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