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dc.contributor.authorNicoletti, Paola
dc.contributor.authorDevarbhavi, Harshad
dc.contributor.authorGoel, Ashish
dc.contributor.authorVenkatesan, Radha
dc.contributor.authorEapen, Chundamannil E
dc.contributor.authorGrove, Jane I
dc.contributor.authorZafer, Samreen
dc.contributor.authorBjornsson, Einar
dc.contributor.authorLucena, M Isabel
dc.contributor.authorAndrade, Raul J
dc.contributor.authorPirmohamed, Munir
dc.contributor.authorWadelius, Mia
dc.contributor.authorLarrey, Dominique
dc.contributor.authorMaitland-van der Zee, Anke-Hilse
dc.contributor.authorIbanez, Luisa
dc.contributor.authorWatkins, Paul B
dc.contributor.authorDaly, Ann K
dc.contributor.authorAithal, Guruprasad P
dc.date.accessioned2021-01-18T14:31:59Z
dc.date.available2021-01-18T14:31:59Z
dc.date.issued2020-11-01
dc.date.submitted2021-01
dc.identifier.citationNicoletti P, Devarbhavi H, Goel A, Venkatesan R, Eapen CE, Grove JI, et al. Genetic Risk Factors in Drug-Induced Liver Injury Due to Isoniazid-Containing Antituberculosis Drug Regimens. Clinical pharmacology and therapeutics. 2020.doi:10.1002/cpt.2100.en_US
dc.identifier.pmid33135175
dc.identifier.doi10.1002/cpt.2100
dc.identifier.urihttp://hdl.handle.net/2336/621630
dc.descriptionTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Downloaden_US
dc.description.abstractDrug-induced liver injury (DILI) is a complication of treatment with antituberculosis (TB) drugs, especially in isoniazid (INH)-containing regimens. To investigate genetic risk factors, we performed a genomewide association study (GWAS) involving anti-TB DILI cases (55 Indian and 70 European) and controls (1,199 Indian and 10,397 European). Most cases were treated with a standard anti-TB drug regimen; all received INH. We imputed single nucleotide polymorphism and HLA genotypes and performed trans-ethnic meta-analysis on GWAS and candidate gene genotypes. GWAS found one significant association (rs117491755) in Europeans only. For HLA, HLA-B*52:01 was significant (meta-analysis odds ratio (OR) 2.67, 95% confidence interval (CI) 1.63-4.37, P = 9.4 × 10-5 ). For N-acetyltransferase 2 (NAT2), NAT2*5 frequency was lower in cases (OR 0.69, 95% CI 0.57-0.83, P = 0.01). NAT2*6 and NAT2*7 were more common, with homozygotes for NAT2*6 and/or NAT2*7 enriched among cases (OR 1.89, 95% CI 0.84-4.22, P = 0.004). We conclude HLA genotype makes a small contribution to TB drug-related DILI and that the NAT2 contribution is complex, but consistent with previous reports when differences in the metabolic effect of NAT2*5 compared with those of NAT2*6 and NAT2*7 are considered.en_US
dc.description.sponsorshipInternational Serious Adverse Events Consortium Abbott Laboratories Amgen Daiichi Sankyo Company Limited GlaxoSmithKline Merck & Company Novartis Pfizer Roche Holding Sanofi-Aventis Takeda Pharmaceutical Company Ltd Wellcome Trust National Institute for Health Research (NIHR) Nottingham Digestive Diseases Biomedical Research Unit NIHR Nottingham Biomedical Research Centre at the Nottingham University Hospitals NHS Trust University of Nottingham Instituto de Salud Carlos III European Union (EU) Instituto de Salud Carlos III Swedish Medical Products Agency Swedish Society of Medicine Swedish Research Council Swedish Heart-Lung Foundation IMI2 TransBioLine Projecten_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.urlhttps://ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.2100en_US
dc.rights© 2020 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.
dc.subjectLifrarsjúkdómaren_US
dc.subjectAukaverkanir lyfjaen_US
dc.subject.meshAntitubercular Agentsen_US
dc.subject.meshChemical and Drug Induced Liver Injuryen_US
dc.subject.meshGenome-Wide Association Studyen_US
dc.titleGenetic Risk Factors in Drug-Induced Liver Injury Due to Isoniazid-Containing Antituberculosis Drug Regimens.en_US
dc.typeArticleen_US
dc.identifier.eissn1532-6535
dc.contributor.department1Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA. 2Department of Gastroenterology, St John's Medical College Hospital, Bangalore, India. 3Christian Medical College, Vellore, India. 4Department of Molecular Genetics, Madras Diabetes Research Foundation, Chennai, India. 5NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, University of Nottingham, UK. 6Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK. 7Division of Gastroenterology and Hepatology, Department of Internal Medicine, The National University Hospital of Iceland, Reykjavik, Iceland. 8Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 9UGC Digestivo y Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain. 10Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain. 11Department of Pharmacology and Therapeutics, Liverpool University Hospitals and Liverpool Health Partners, University of Liverpool, Liverpool, UK. 12Department of Medical Sciences and Science for Life Laboratory, Uppsala University, Uppsala, Sweden. 13Liver Unit, CHU St. Eloi Hospital, Montpellier, France. 14Department of Respiratory Medicine, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, Netherlands. 15Division of Pharmacoepidemiology and Clinical Pharmacology, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands. 16Fundació Institut Català de Farmacologia, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. 17Eshelman School of Pharmacy, University of North Carolina Institute for Drug Safety Sciences, Chapel Hill, North Carolina, USA. 18Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.en_US
dc.identifier.journalClinical pharmacology and therapeuticsen_US
dc.rights.accessOpen Access - Opinn aðganguren_US
dc.departmentcodeGAS12
dc.source.journaltitleClinical pharmacology and therapeutics
refterms.dateFOA2021-01-18T14:32:00Z
dc.source.countryUnited Kingdom
dc.source.countryUnited States


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