PMID- 30661239
OWN - NLM
STAT- MEDLINE
DCOM- 20200330
LR  - 20210109
IS  - 1532-6535 (Electronic)
IS  - 0009-9236 (Linking)
VI  - 106
IP  - 1
DP  - 2019 Jul
TI  - Drug-Induced Liver Injury due to Flucloxacillin: Relevance of Multiple Human 
      Leukocyte Antigen Alleles.
PG  - 245-253
LID - 10.1002/cpt.1375 [doi]
AB  - Some patients prescribed flucloxacillin (~ 0.01%) develop drug-induced liver 
      injury (DILI). HLA-B*57:01 is an established genetic risk factor for 
      flucloxacillin DILI. To consolidate this finding, identify additional genetic 
      factors, and assess relevance of risk factors for flucloxacillin DILI in relation 
      to DILI due to other penicillins, we performed a genomewide association study 
      involving 197 flucloxacillin DILI cases and 6,835 controls. We imputed 
      single-nucleotide polymorphism and human leukocyte antigen (HLA) genotypes. 
      HLA-B*57:01 was the major risk factor (allelic odds ratio (OR) = 36.62; 
      P = 2.67 x 10(-97) ). HLA-B*57:03 also showed an association (OR = 79.21; 
      P = 1.2 x 10(-6) ). Within the HLA-B protein sequence, imputation showed 
      valine(97) , common to HLA-B*57:01 and HLA-B*57:03, had the largest effect 
      (OR = 38.1; P = 9.7 x 10(-97) ). We found no HLA-B*57 association with DILI due 
      to other isoxazolyl penicillins (n = 6) or amoxicillin (n = 15) and no 
      significant non-HLA signals for any penicillin-related DILI.
CI  - (c) 2019 The Authors Clinical Pharmacology & Therapeutics (c) 2019 American Society 
      for Clinical Pharmacology and Therapeutics.
FAU - Nicoletti, Paola
AU  - Nicoletti P
AD  - Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount 
      Sinai, New York, New York, USA.
AD  - Sema4, a Mount Sinai Venture, Stamford, Connecticut, USA.
FAU - Aithal, Guruprasad P
AU  - Aithal GP
AD  - National Institute for Health Research (NIHR) Nottingham Biomedical Research 
      Centre, Nottingham University Hospital NHS Trust and University of Nottingham, 
      Nottingham, UK.
FAU - Chamberlain, Thomas C
AU  - Chamberlain TC
AD  - Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
AD  - University of British Columbia, Vancouver, British Columbia, Canada.
FAU - Coulthard, Sally
AU  - Coulthard S
AD  - Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
FAU - Alshabeeb, Mohammad
AU  - Alshabeeb M
AD  - Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
AD  - Developmental Medicine Department, King Abdullah International Medical Research 
      Center, Riyadh, Kingdom of Saudi Arabia.
FAU - Grove, Jane I
AU  - Grove JI
AD  - National Institute for Health Research (NIHR) Nottingham Biomedical Research 
      Centre, Nottingham University Hospital NHS Trust and University of Nottingham, 
      Nottingham, UK.
AD  - Nottingham Digestive Diseases Centre, School of Medicine, University of 
      Nottingham, Nottingham, UK.
FAU - Andrade, Raul J
AU  - Andrade RJ
AD  - UGC Digestivo y Servicio de Farmacologia Clinica, Instituto de Investigacion 
      Biomedica de Malaga (IBIMA), Hospital Universitario Virgen de la Victoria, 
      Universidad de Malaga, Malaga, Spain.
AD  - Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas 
      (CIBERehd), Madrid, Spain.
FAU - Bjornsson, Einar
AU  - Bjornsson E
AD  - Division of Gastroenterology and Hepatology, Department of Internal Medicine, The 
      National University Hospital of Iceland, Reykjavik, Iceland.
FAU - Dillon, John F
AU  - Dillon JF
AD  - Medical Research Institute, University of Dundee, Ninewells Hospital, Dundee, UK.
FAU - Hallberg, Par
AU  - Hallberg P
AD  - Department of Medical Sciences and Science for Life Laboratory, Uppsala 
      University, Uppsala, Sweden.
FAU - Lucena, M Isabel
AU  - Lucena MI
AD  - UGC Digestivo y Servicio de Farmacologia Clinica, Instituto de Investigacion 
      Biomedica de Malaga (IBIMA), Hospital Universitario Virgen de la Victoria, 
      Universidad de Malaga, Malaga, Spain.
AD  - Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas 
      (CIBERehd), Madrid, Spain.
FAU - Maitland-van der Zee, Anke H
AU  - Maitland-van der Zee AH
AD  - Department of Respiratory Medicine, Academic Medical Center (AMC), University of 
      Amsterdam, Amsterdam, The Netherlands.
FAU - Martin, Jennifer H
AU  - Martin JH
AD  - School of Medicine and Public Health, University of Newcastle, Callaghan, New 
      South Wales, Australia.
FAU - Molokhia, Mariam
AU  - Molokhia M
AD  - School of Population Health and Environmental Sciences, Faculty of Life Sciences 
      and Medicine, King's College, London, UK.
FAU - Pirmohamed, Munir
AU  - Pirmohamed M
AD  - Department of Molecular and Clinical Pharmacology, University of Liverpool, 
      Liverpool, UK.
FAU - Wadelius, Mia
AU  - Wadelius M
AD  - Department of Medical Sciences and Science for Life Laboratory, Uppsala 
      University, Uppsala, Sweden.
FAU - Shen, Yufeng
AU  - Shen Y
AD  - The Herbert Irving Comprehensive Cancer Center, Columbia University, New York, 
      New York, USA.
AD  - Department of Biomedical Informatics, Columbia University, New York, New York, 
      USA.
FAU - Nelson, Matthew R
AU  - Nelson MR
AD  - Target Sciences, GSK, King of Prussia, Pennsylvania, USA.
FAU - Daly, Ann K
AU  - Daly AK
AD  - Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
CN  - International Drug-Induced Liver Injury Consortium (iDILIC)
LA  - eng
GR  - BRC-1215-20003/DH_/Department of Health/United Kingdom
GR  - MR/L006758/1/MRC_/Medical Research Council/United Kingdom
GR  - BB_/Biotechnology and Biological Sciences Research Council/United Kingdom
GR  - MR/N005953/1/MRC_/Medical Research Council/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190319
PL  - United States
TA  - Clin Pharmacol Ther
JT  - Clinical pharmacology and therapeutics
JID - 0372741
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (HLA-B Antigens)
RN  - 0 (Penicillins)
RN  - 43B2M34G2V (Floxacillin)
SB  - IM
MH  - Aged
MH  - Anti-Bacterial Agents/*adverse effects
MH  - Chemical and Drug Induced Liver Injury/*genetics
MH  - Female
MH  - Floxacillin/*adverse effects
MH  - Genome-Wide Association Study
MH  - Genotype
MH  - HLA-B Antigens/*genetics
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Penicillins/adverse effects
MH  - Polymorphism, Single Nucleotide
EDAT- 2019/01/21 06:00
MHDA- 2020/03/31 06:00
CRDT- 2019/01/21 06:00
PHST- 2018/08/23 00:00 [received]
PHST- 2018/12/13 00:00 [accepted]
PHST- 2019/01/21 06:00 [pubmed]
PHST- 2020/03/31 06:00 [medline]
PHST- 2019/01/21 06:00 [entrez]
AID - 10.1002/cpt.1375 [doi]
PST - ppublish
SO  - Clin Pharmacol Ther. 2019 Jul;106(1):245-253. doi: 10.1002/cpt.1375. Epub 2019 
      Mar 19.