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Drug-induced injury due to flucloxacillin: relevance of multiple HLA alleles.

Clin Pharmacol Ther. 2019 Jan 19;:

Authors: 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, International Drug-induced Liver Injury consortium (iDILIC)

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=2.67×10-97 ). HLA-B*57:03 also showed an association (OR=79.21, P=1.2×10-6 ). 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=9.7×10-97 ). 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. This article is protected by copyright. All rights reserved.

PMID: 30661239 [PubMed – as supplied by publisher]

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