Drug-induced liver injury due to Flucloxacillin: relevance of multiple human leukocyte antigen alleles

Nicoletti, Paola; Aithal, Guruprasad P.; Lucena, M. Isabel; Maitland-van der Zee, Anke H.; Martin, Jennifer H.; Molokhia, Mariam; Pirmohamed, Munir; Wadelius, Mia; Shen, Yufeng; Nelson, Matthew R.; Daly, Ann K.; Chamberlain, Thomas C.; Coulthard, Sally; Alshabeeb, Mohammad; Grove, Jane I.; Andrade, Raul J.; Bjornsson, Einar; Dillon, John F.; Hallberg, Par

Title: Drug-induced liver injury due to Flucloxacillin: relevance of multiple human leukocyte antigen alleles
Creator: Nicoletti, Paola; Aithal, Guruprasad P.; Lucena, M. Isabel; Maitland-van der Zee, Anke H.; Martin, Jennifer H.; Molokhia, Mariam; Pirmohamed, Munir; Wadelius, Mia; Shen, Yufeng; Nelson, Matthew R.; Daly, Ann K.; Chamberlain, Thomas C.; Coulthard, Sally; Alshabeeb, Mohammad; Grove, Jane I.; Andrade, Raul J.; Bjornsson, Einar; Dillon, John F.; Hallberg, Par
Relation: Clinical Pharmacology and Therapeutics Vol. 106, Issue 1, p. 245-253
Publisher Link: http://dx.doi.org/10.1002/cpt.1375
Publisher: John Wiley & Sons
Resource Type: journal article
Date: 2019
Description: 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 valine⁹⁷, 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.
Subject: flucloxacillin; genetic risk factor; drug-induced liver injury; amino acid
Identifier: http://hdl.handle.net/1959.13/1466997
Identifier: uon:47712
Identifier: ISSN:0009-9236
Language: eng
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