2026-08-29T09:10:52Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/178872024-02-10T20:01:51Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927

00925njm 22002777a 4500 dc Nicoletti, Paola author Barrett, Sarah author McEvoy, Laurence author Daly, Ann K author Aithal, Guruprasad author Lucena, M Isabel author Andrade, Raul J author Wadelius, Mia author Hallberg, Pär author Stephens, Camilla author Bjornsson, Einar S author Friedmann, Peter author Kainu, Kati author Laitinen, Tarja author Marson, Anthony author Molokhia, Mariam author Phillips, Elizabeth author Pichler, Werner author Romano, Antonino author Shear, Neil author Sills, Graeme author Tanno, Luciana K author Swale, Ashley author Floratos, Aris author Shen, Yufeng author Nelson, Matthew R author Watkins, Paul B author Daly, Mark J author Morris, Andrew P author Alfirevic, Ana author Pirmohamed, Munir author 2019-07-03 Carbamazepine (CBZ) causes life-threating T-cell-mediated hypersensitivity reactions, including serious cutaneous adverse reactions (SCARs) and drug-induced liver injury (CBZ-DILI). In order to evaluate shared or phenotype-specific genetic predisposing factors for CBZ hypersensitivity reactions, we performed a meta-analysis of two genomewide association studies (GWAS) on a total of 43 well-phenotyped Northern and Southern European CBZ-SCAR cases and 10,701 population controls and a GWAS on 12 CBZ-DILI cases and 8,438 ethnically matched population controls. HLA-A*31:01 was identified as the strongest genetic predisposing factor for both CBZ-SCAR (odds ratio (OR) = 8.0; 95% CI 4.10-15.80; P = 1.2 × 10-9 ) and CBZ-DILI (OR = 7.3; 95% CI 2.47-23.67; P = 0.0004) in European populations. The association with HLA-A*31:01 in patients with SCAR was mainly driven by hypersensitivity syndrome (OR = 12.9; P = 2.1 × 10-9 ) rather than by Stevens-Johnson syndrome/toxic epidermal necrolysis cases, which showed an association with HLA-B*57:01. We also identified a novel risk locus mapping to ALK only for CBZ-SCAR cases, which needs replication in additional cohorts and functional evaluation. 10.1002/cpt.1493 1532-6535 Clinical pharmacology and therapeutics http://hdl.handle.net/10668/13926 31066027 http://hdl.handle.net/20.500.12105/17887 Shared Genetic Risk Factors Across Carbamazepine-Induced Hypersensitivity Reactions.