2026-08-29T09:10:52Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/178872024-02-10T20:01:51Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud
author
Nicoletti, Paola
author
Barrett, Sarah
author
McEvoy, Laurence
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Daly, Ann K
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Aithal, Guruprasad
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Lucena, M Isabel
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Andrade, Raul J
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Wadelius, Mia
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Hallberg, Pär
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Stephens, Camilla
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Bjornsson, Einar S
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Friedmann, Peter
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Kainu, Kati
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Laitinen, Tarja
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Marson, Anthony
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Molokhia, Mariam
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Phillips, Elizabeth
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Pichler, Werner
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Romano, Antonino
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Shear, Neil
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Sills, Graeme
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Tanno, Luciana K
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Swale, Ashley
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Floratos, Aris
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Shen, Yufeng
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Nelson, Matthew R
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Watkins, Paul B
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Daly, Mark J
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Morris, Andrew P
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Alfirevic, Ana
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Pirmohamed, Munir
2024-02-10T20:01:51Z
2024-02-10T20:01:51Z
2019-07-03
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
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.
eng
Shared Genetic Risk Factors Across Carbamazepine-Induced Hypersensitivity Reactions.
research article