RT Journal Article
T1 Shared Genetic Risk Factors Across Carbamazepine-Induced Hypersensitivity Reactions.
A1 Nicoletti, Paola
A1 Barrett, Sarah
A1 McEvoy, Laurence
A1 Daly, Ann K
A1 Aithal, Guruprasad
A1 Lucena, M Isabel
A1 Andrade, Raul J
A1 Wadelius, Mia
A1 Hallberg, Pär
A1 Stephens, Camilla
A1 Bjornsson, Einar S
A1 Friedmann, Peter
A1 Kainu, Kati
A1 Laitinen, Tarja
A1 Marson, Anthony
A1 Molokhia, Mariam
A1 Phillips, Elizabeth
A1 Pichler, Werner
A1 Romano, Antonino
A1 Shear, Neil
A1 Sills, Graeme
A1 Tanno, Luciana K
A1 Swale, Ashley
A1 Floratos, Aris
A1 Shen, Yufeng
A1 Nelson, Matthew R
A1 Watkins, Paul B
A1 Daly, Mark J
A1 Morris, Andrew P
A1 Alfirevic, Ana
A1 Pirmohamed, Munir
AB 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.
YR 2019
FD 2019-07-03
LK http://hdl.handle.net/10668/13926
UL http://hdl.handle.net/10668/13926
LA en
DS RISalud
RD Apr 11, 2025