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Lookup NU author(s): Dr Tom Chamberlain, Dr Sally Coulthard, Mohammad Alshabeeb, Professor Ann DalyORCiD
This is the authors' accepted manuscript of an article that has been published in its final definitive form by John Wiley & Sons, Inc., 2019.
For re-use rights please refer to the publisher's terms and conditions.
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 genome-wide association study involving 197 flucloxacillin DILI cases and 6835 controls. We imputed SNP and HLA genotypes. HLA-B*57:01 was the major risk factor (allelic OR=36.62, P=2.67x10-97). HLA-B*57:03 also showed an association (OR=79.21, P=1.2x10-6). Within the HLA-B protein sequence, imputation showed valine97, common to HLA-B*57:01 and HLA-B*57:03, had the largest effect (OR=38.1, P=9.7x10-97). 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.
Author(s): Nicoletti P, Aithal GP, Chamberlain TC, Coulthard S, Alshabeeb M, Grove JI, Andrade RJ, Bjornsson E, Dillon JF, Hallberg P, Lucena MI, Maitland-van der Zee AH, Martin JH, Molokhia M, Pirmohamed M, Wadelius M, Shen Y, Nelson MR, Daly AK
Publication type: Article
Publication status: Published
Journal: Clinical Pharmacology & Therapeutics
Year: 2019
Volume: 106
Issue: 1
Pages: 245-253
Print publication date: 01/07/2019
Online publication date: 19/01/2019
Acceptance date: 17/12/2018
Date deposited: 19/12/2018
ISSN (print): 0009-9236
ISSN (electronic): 1532-6535
Publisher: John Wiley & Sons, Inc.
URL: https://doi.org/10.1002/cpt.1375
DOI: 10.1002/cpt.1375
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