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Investigation of Oxidative Stress-Related Candidate Genes as Risk Factors for Drug-Induced Liver Injury due to Co-Amoxiclav.
DNA Cell Biol. 2020 Mar; 39(3):349-354.DC

Abstract

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.

Authors+Show Affiliations

Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom. Department of Developmental Medicine, King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia. King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, United Kingdom. Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, United Kingdom.Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31905014

Citation

Alshabeeb, Mohammad A., et al. "Investigation of Oxidative Stress-Related Candidate Genes as Risk Factors for Drug-Induced Liver Injury Due to Co-Amoxiclav." DNA and Cell Biology, vol. 39, no. 3, 2020, pp. 349-354.
Alshabeeb MA, Aithal GP, Daly AK. Investigation of Oxidative Stress-Related Candidate Genes as Risk Factors for Drug-Induced Liver Injury due to Co-Amoxiclav. DNA Cell Biol. 2020;39(3):349-354.
Alshabeeb, M. A., Aithal, G. P., & Daly, A. K. (2020). Investigation of Oxidative Stress-Related Candidate Genes as Risk Factors for Drug-Induced Liver Injury due to Co-Amoxiclav. DNA and Cell Biology, 39(3), 349-354. https://doi.org/10.1089/dna.2019.4982
Alshabeeb MA, Aithal GP, Daly AK. Investigation of Oxidative Stress-Related Candidate Genes as Risk Factors for Drug-Induced Liver Injury Due to Co-Amoxiclav. DNA Cell Biol. 2020;39(3):349-354. PubMed PMID: 31905014.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Investigation of Oxidative Stress-Related Candidate Genes as Risk Factors for Drug-Induced Liver Injury due to Co-Amoxiclav. AU - Alshabeeb,Mohammad A, AU - Aithal,Guruprasad P, AU - Daly,Ann K, Y1 - 2020/01/06/ PY - 2020/1/7/pubmed PY - 2020/3/20/medline PY - 2020/1/7/entrez KW - GPX1 KW - GSTM1 KW - GSTT1 KW - SOD2 KW - amoxicillin–clavulanic acid KW - co-amoxiclav KW - drug-induced liver injury (DILI) KW - oxidative stress genes SP - 349 EP - 354 JF - DNA and cell biology JO - DNA Cell Biol VL - 39 IS - 3 N2 - 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. SN - 1557-7430 UR - https://www.unboundmedicine.com/medline/citation/31905014/Investigation_of_Oxidative_Stress_Related_Candidate_Genes_as_Risk_Factors_for_Drug_Induced_Liver_Injury_due_to_Co_Amoxiclav_ L2 - https://www.liebertpub.com/doi/10.1089/dna.2019.4982?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -