Shared genetic risk factors across carbamazepine‐induced hypersensitivity reactions
2019
Carbamazepine (CBZ) causes life-threating T-cell mediated hypersensitivity reactions (CBZ-HRs) including serious cutaneous adverse reactions (SCAR) and liver injury (CBZ-DILI). In order to evaluate shared or phenotype-specific genetic predisposing factors for CBZ-HRs, we performed a meta-analysis of two GWAS studies 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 (OR= 8.0; 95% CI 4.10-15.80; P=1.2x10-9 ) 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 SCAR patients was mainly driven by hypersensitivity syndrome (OR = 12.9; P=2.1x10-9 ) rather than by Stevens-Johnson Syndrome/toxic epidermal necolysis (SJS/TEN) 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. This article is protected by copyright. All rights reserved.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
49
References
26
Citations
NaN
KQI