https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 Drug-induced liver injury due to Flucloxacillin: relevance of multiple human leukocyte antigen alleles https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47712 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.]]> Tue 21 Mar 2023 18:39:29 AEDT ]]> A missense variant in PTPN22 is a risk factor for drug-induced liver injury https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44100 –9 and replicated the finding in the validation set (OR 1.48; 95% CI 1.09–1.99; P = .01). The minor allele frequency showed the same effect size (OR > 1) among ethnic groups. The strongest association was with amoxicillin and clavulanate-associated DILI in persons of European ancestry (OR 1.62; 95% CI 1.32–1.98; P = 4.0 × 10–6; allele frequency = 13.3%), but the polymorphism was associated with DILI of other causes (OR 1.37; 95% CI 1.21–1.56; P = 1.5 × 10–6; allele frequency = 11.5%). Among amoxicillin- and clavulanate-associated cases of European ancestry, rs2476601 doubled the risk for DILI among those with the HLA risk alleles A*02:01 and DRB1*15:01. Conclusions: In a genome-wide association study, we identified rs2476601 in PTPN22 as a non-HLA variant that associates with risk of liver injury caused by multiple drugs and validated our finding in a separate cohort. This variant has been associated with increased risk of autoimmune diseases, providing support for the concept that alterations in immune regulation contribute to idiosyncratic DILI.]]> Fri 07 Oct 2022 14:21:42 AEDT ]]>