Shared Genetic Risk Factors Across Carbamazepine-Induced Hypersensitivity Reactions.
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Daly, Ann K
Lucena, M Isabel
Andrade, Raul J
Bjornsson, Einar S
Tanno, Luciana K
Nelson, Matthew R
Watkins, Paul B
Daly, Mark J
Morris, Andrew P
MetadataShow full item record
CitationNicoletti P, Barrett S, McEvoy L, Daly AK, Aithal G, Lucena MI, Andrade RJ, Wadelius M, Hallberg P, Stephens C, Bjornsson ES. Shared genetic risk factors across carbamazepine‐induced hypersensitivity reactions. Clinical Pharmacology & Therapeutics. 2019, 105(5):1028-36.
AbstractCarbamazepine (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.
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- Issue date: 2014 Feb
- Genetic variants associated with severe cutaneous adverse drug reactions induced by carbamazepine.
- Authors: Nakkam N, Konyoung P, Amornpinyo W, Saksit N, Tiamkao S, Khunarkornsiri U, Khaeso K, Pattanacheewapull O, Jorns TP, Chumworathayi P, Tassaneeyakul W
- Issue date: 2022 Feb
- Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions.
- Authors: Hung SI, Chung WH, Jee SH, Chen WC, Chang YT, Lee WR, Hu SL, Wu MT, Chen GS, Wong TW, Hsiao PF, Chen WH, Shih HY, Fang WH, Wei CY, Lou YH, Huang YL, Lin JJ, Chen YT
- Issue date: 2006 Apr
- Association of the HLA-B alleles with carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in the Javanese and Sundanese population of Indonesia: the important role of the HLA-B75 serotype.
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- Issue date: 2017 Dec
- HLA-A 31:01 and HLA-B 15:02 as genetic markers for carbamazepine hypersensitivity in children.
- Authors: Amstutz U, Ross CJ, Castro-Pastrana LI, Rieder MJ, Shear NH, Hayden MR, Carleton BC, CPNDS Consortium.
- Issue date: 2013 Jul