Identification of Reduced ERAP2 Expression and a Novel HLA Allele as Components of a Risk Score for Susceptibility to Liver Injury Due to Amoxicillin-Clavulanate.

Humans Anti-Bacterial Agents / adverse effects Alleles HLA-DRB1 Chains / genetics Genome-Wide Association Study Amoxicillin-Potassium Clavulanate Combination Liver Risk Factors HLA-A Antigens / genetics Chemical and Drug Induced Liver Injury / genetics Polymorphism, Single Nucleotide Genetic Predisposition to Disease Protein Tyrosine Phosphatase, Non-Receptor Type 22 / genetics Aminopeptidases / genetics
Amoxicillin-Clavulanate DILI ERAP2 GWAS HLA-B∗15:18

Journal

Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630

Informations de publication

Date de publication:
03 2023
Historique:
received: 24 06 2022
revised: 21 11 2022
accepted: 28 11 2022
pmc-release: 01 03 2024
pubmed: 11 12 2022
medline: 3 3 2023
entrez: 10 12 2022
Statut: ppublish

Résumé

Drug-induced liver injury (DILI) due to amoxicillin-clavulanate (AC) has been associated with HLA-A∗02:01, HLA-DRB1∗15:01, and rs2476601, a missense variant in PTPN22. The aim of this study was to identify novel risk factors for AC-DILI and to construct a genetic risk score (GRS). Transcriptome-wide association study and genome-wide association study analyses were performed on 444 AC-DILI cases and 10,397 population-based controls of European descent. Associations were confirmed in a validation cohort (n = 133 cases and 17,836 population-based controls). Discovery and validation AC-DILI cases were also compared with 1358 and 403 non-AC-DILI cases. Transcriptome-wide association study revealed a significant association of AC-DILI risk with reduced liver expression of ERAP2 (P = 3.7 × 10 We identified novel associations of AC-DILI risk with ERAP2 low expression and with HLA-B∗15:18. GRS based on the 5 risk variants may assist AC-DILI causality assessment and risk management.

Sections du résumé

BACKGROUND & AIMS
Drug-induced liver injury (DILI) due to amoxicillin-clavulanate (AC) has been associated with HLA-A∗02:01, HLA-DRB1∗15:01, and rs2476601, a missense variant in PTPN22. The aim of this study was to identify novel risk factors for AC-DILI and to construct a genetic risk score (GRS).
METHODS
Transcriptome-wide association study and genome-wide association study analyses were performed on 444 AC-DILI cases and 10,397 population-based controls of European descent. Associations were confirmed in a validation cohort (n = 133 cases and 17,836 population-based controls). Discovery and validation AC-DILI cases were also compared with 1358 and 403 non-AC-DILI cases.
RESULTS
Transcriptome-wide association study revealed a significant association of AC-DILI risk with reduced liver expression of ERAP2 (P = 3.7 × 10
CONCLUSIONS
We identified novel associations of AC-DILI risk with ERAP2 low expression and with HLA-B∗15:18. GRS based on the 5 risk variants may assist AC-DILI causality assessment and risk management.

Identifiants

DOI: 10.1053/j.gastro.2022.11.036 PMID: 36496055 PMC: PMC9974860
pubmed: 36496055
pii: S0016-5085(22)01374-9
doi: 10.1053/j.gastro.2022.11.036
pmc: PMC9974860
mid: NIHMS1855942
pii:
doi:

Substances chimiques

Anti-Bacterial Agents 0
HLA-DRB1 Chains 0
Amoxicillin-Potassium Clavulanate Combination 74469-00-4
HLA-A Antigens 0
PTPN22 protein, human EC 3.1.3.48
Protein Tyrosine Phosphatase, Non-Receptor Type 22 EC 3.1.3.48
ERAP2 protein, human EC 3.4.11.-
Aminopeptidases EC 3.4.11.-

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

454-466

Subventions

Organisme : NIDDK NIH HHS
ID : U01 DK065211
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR025761
Pays : United States
Organisme : Department of Health
ID : BRC-1215-20003
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : U24 DK065176
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK065238
Pays : United States
Organisme : NIMH NIH HHS
ID : RC2 MH089964
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK083023
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG004438
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG004424
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK082992
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG004608
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK083027
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK083020
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG006781
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK065201
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK100928
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK065193
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA155309
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH084098
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG007417
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK065176
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG004603
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR025747
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR024986
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK065184
Pays : United States

Informations de copyright

Copyright © 2023 AGA Institute. All rights reserved.

Références

Ann Rheum Dis. 2022 Mar;81(3):406-415
pubmed: 34789453
Drug Saf. 2009;32(1):55-68
pubmed: 19132805
Hepatology. 2010 Dec;52(6):2065-76
pubmed: 20949552
Toxicol Sci. 2020 Nov 1;178(1):115-126
pubmed: 32777075
Clin Pharmacol Ther. 2020 Jun;107(6):1383-1393
pubmed: 31868224
PLoS One. 2013 Jul 09;8(7):e68111
pubmed: 23874514
Sci Rep. 2014 Jul 21;4:5762
pubmed: 25042059
Clin Pharmacol Ther. 2011 Jun;89(6):806-15
pubmed: 21544079
Rheum Dis Clin North Am. 2012 Aug;38(3):539-53
pubmed: 23083754
Nat Genet. 2015 Sep;47(9):1091-8
pubmed: 26258848
Clin Pharmacol Ther. 2019 Jul;106(1):245-253
pubmed: 30661239
J Invest Dermatol. 2011 Dec;131(12):2386-93
pubmed: 21833018
Gastroenterology. 2019 May;156(6):1707-1716.e2
pubmed: 30664875
Hum Mol Genet. 2018 Dec 15;27(24):4333-4343
pubmed: 30215709
Hepatology. 2006 Oct;44(4):850-6
pubmed: 17006920
Nat Genet. 2021 Aug;53(8):1243-1249
pubmed: 34326547
Hum Immunol. 2019 May;80(5):310-317
pubmed: 30414458
Gastroenterology. 2017 Apr;152(5):1078-1089
pubmed: 28043905
Nat Rev Genet. 2009 Jun;10(6):392-404
pubmed: 19434077
Hepatology. 2021 Jan;73(1):268-281
pubmed: 32270503
Cancer. 1950 Jan;3(1):32-5
pubmed: 15405679
Nat Rev Rheumatol. 2014 Oct;10(10):602-11
pubmed: 25003765
J Hepatol. 2018 Oct;69(4):948-957
pubmed: 29792895
Dig Dis Sci. 2016 Aug;61(8):2406-2416
pubmed: 27003146
Gastroenterology. 2013 Jun;144(7):1419-25, 1425.e1-3; quiz e19-20
pubmed: 23419359
Gastroenterology. 2015 Jun;148(7):1340-52.e7
pubmed: 25754159
Nat Genet. 2016 Oct;48(10):1284-1287
pubmed: 27571263
Mol Immunol. 2014 Jan;57(1):12-21
pubmed: 23916068
Am J Hum Genet. 2007 Sep;81(3):559-75
pubmed: 17701901
PLoS Genet. 2010 Oct 14;6(10):e1001157
pubmed: 20976248
Am J Gastroenterol. 2017 Sep;112(9):1382-1388
pubmed: 28762375
Bioinformatics. 2010 Sep 15;26(18):2336-7
pubmed: 20634204
Adv Pharmacol. 2019;85:165-193
pubmed: 31307586
Gastroenterology. 2011 Jul;141(1):338-47
pubmed: 21570397
Pharmacogenomics J. 2014 Apr;14(2):192-200
pubmed: 23712092
Curr Opin Rheumatol. 2015 Jul;27(4):349-56
pubmed: 26002026

Auteurs

Paola Nicoletti (P)

Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: paola.nicoletti@mssm.edu.

Andrew Dellinger (A)

Duke Molecular Physiology Institute, Duke University, Durham, North Carolina.

Yi Ju Li (YJ)

Duke Molecular Physiology Institute, Duke University, Durham, North Carolina; Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina.

Huiman X Barnhart (HX)

Duke Molecular Physiology Institute, Duke University, Durham, North Carolina; Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina.

Naga Chalasani (N)

Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana.

Robert J Fontana (RJ)

University of Michigan, Ann Arbor, Michigan.

Joseph A Odin (JA)

Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.

Jose Serrano (J)

National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland.

Andrew Stolz (A)

University of Southern California, Los Angeles, California.

Amy S Etheridge (AS)

University of North Carolina Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Federico Innocenti (F)

University of North Carolina Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Olivier Govaere (O)

Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.

Jane I Grove (JI)

Nottingham Digestive Diseases Centre and National Institute for Health Research Nottingham Biomedical Research Centre at the Nottingham University Hospital National Health Service Trust, Nottingham, United Kingdom; University of Nottingham, Nottingham, United Kingdom.

Camilla Stephens (C)

Servicios de Digestivo y Farmacologia Clínica, Instituto de Investigación Biomédica de Málaga (IBIMA_Plataforma Bionand), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.

Guruprasad P Aithal (GP)

Nottingham Digestive Diseases Centre and National Institute for Health Research Nottingham Biomedical Research Centre at the Nottingham University Hospital National Health Service Trust, Nottingham, United Kingdom; University of Nottingham, Nottingham, United Kingdom.

Raul J Andrade (RJ)

Servicios de Digestivo y Farmacologia Clínica, Instituto de Investigación Biomédica de Málaga (IBIMA_Plataforma Bionand), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.

Einar S Bjornsson (ES)

Department of Internal Medicine, Landspitali University Hospital, Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

Ann K Daly (AK)

Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.

M Isabel Lucena (MI)

Servicios de Digestivo y Farmacologia Clínica, Instituto de Investigación Biomédica de Málaga (IBIMA_Plataforma Bionand), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.

Paul B Watkins (PB)

University of North Carolina Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; University of North Carolina Institute for Drug Safety Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Identification of Reduced ERAP2 Expression and...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antibactériens › Identification of Reduced ERAP2 Expression and...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Allèles › Identification of Reduced ERAP2 Expression and...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Isoantigènes › Antigènes d'histocompatibilité › Antigènes HLA › Antigènes HLA-D › Antigènes HLA-DR › Chaines bêta des antigènes HLA-DR › Chaines HLA-DRB1 › Identification of Reduced ERAP2 Expression and...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Identification of Reduced ERAP2 Expression and...
questionsmedicales.fr › Préparations pharmaceutiques › Association médicamenteuse › Association amoxicilline-clavulanate de potassium › Identification of Reduced ERAP2 Expression and...
questionsmedicales.fr › Système digestif › Foie › Identification of Reduced ERAP2 Expression and...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Probabilité › Risque › Facteurs de risque › Identification of Reduced ERAP2 Expression and...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Isoantigènes › Antigènes d'histocompatibilité › Antigènes HLA › Antigènes HLA-A › Identification of Reduced ERAP2 Expression and...
questionsmedicales.fr › Troubles dus à des produits chimiques › Intoxication › Lésions hépatiques dues aux substances › Identification of Reduced ERAP2 Expression and...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Identification of Reduced ERAP2 Expression and...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Identification of Reduced ERAP2 Expression and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein Tyrosine Phosphatases › Protein Tyrosine Phosphatases, Non-Receptor › Protein Tyrosine Phosphatase, Non-Receptor Type 22 › Identification of Reduced ERAP2 Expression and...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Peptide hydrolases › Exopeptidases › Aminopeptidases › Identification of Reduced ERAP2 Expression and...