Shared Genetic Risk Factors Across Carbamazepine-Induced Hypersensitivity Reactions.
Clin Pharmacol Ther
; 106(5): 1028-1036, 2019 11.
Article
en En
| MEDLINE
| ID: mdl-31066027
ABSTRACT
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*3101 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*3101 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*5701. We also identified a novel risk locus mapping to ALK only for CBZ-SCAR cases, which needs replication in additional cohorts and functional evaluation.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Carbamazepina
/
Antígenos HLA-A
/
Hipersensibilidad a las Drogas
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Systematic_reviews
Límite:
Adult
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Female
/
Humans
/
Male
País/Región como asunto:
Europa
Idioma:
En
Revista:
Clin Pharmacol Ther
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos