Nicoletti, PaolaAithal, Guruprasad PChamberlain, Thomas CCoulthard, SallyAlshabeeb, MohammadGrove, Jane IAndrade, Raul JBjornsson, EinarDillon, John FHallberg, ParLucena, M IsabelMaitland-van der Zee, Anke HMartin, Jennifer HMolokhia, MariamPirmohamed, MunirWadelius, MiaShen, YufengNelson, Matthew RDaly, Ann K2023-01-252023-01-252018-12-13Nicoletti P, Aithal GP, Chamberlain TC, Coulthard S, Alshabeeb M, Grove JI, et al. Drug-Induced Liver Injury due to Flucloxacillin: Relevance of Multiple Human Leukocyte Antigen Alleles. Clin Pharmacol Ther. 2019 Jul;106(1):245-253http://hdl.handle.net/10668/13436Some 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 × 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.enAnti-bacterial agentsLiver injuryFloxacillinHLA-B antigensAgedAnti-bacterial agentsChemical and drug induced liver injuryFemaleFloxacillinGenome-wide association studyGenotypeHLA-B antigensHumansMaleMiddle agedPenicillinsPolymorphism, single nucleotideresearch article30661239open accessAntibacterianosAntígenos HLA-BEstudio de asociación del genoma completoFloxacilinaGenotipoPenicilinasPolimorfismo de nucleótido simple10.1002/cpt.13751532-6535https://discovery.dundee.ac.uk/ws/files/30359629/FlucloxacillinCPT.pdf