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Clin Pharmacol Ther. 2013 Jul;94(1):142-9. doi: 10.1038/clpt.2013.55. Epub 2013 Mar 18.

HLA-A 31:01 and HLA-B 15:02 as genetic markers for carbamazepine hypersensitivity in children.

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1
Division of Translational Therapeutics, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.

Abstract

The occurrence of hypersensitivity reactions including rare but life-threatening Stevens-Johnson syndrome (SJS) and drug-induced hypersensitivity syndrome (HSS) limits the use of the anticonvulsant carbamazepine (CBZ). Human leukocyte antigen-B (HLA)-B 15:02 and HLA-A 31:01 have been identified as predictive genetic markers for CBZ hypersensitivity in Asian and European patients. To replicate these genetic associations in pediatric patients from North America with a diverse ethnic background, we investigated HLA-A 31:01 and HLA-B 15:02 in 42 children with CBZ hypersensitivity and 91 CBZ-tolerant children from across Canada. HLA-A 31:01 was significantly associated with CBZ-HSS (odds ratio (OR): 26.4, P = 0.0025) and maculopapular exanthema (MPE) (OR: 8.6, P = 0.0037) but not with CBZ-SJS. Conversely, HLA-B 15:02 was associated with CBZ-SJS (OR: 38.6, P = 0.002) but not HSS or MPE. This study is the first to demonstrate the association of HLA-A 31:01 with CBZ hypersensitivity in children, providing important replication of this association and highlighting the importance of HLA-A 31:01 as a predictive biomarker across various ancestries.

PMID:
23588310
PMCID:
PMC3839910
DOI:
10.1038/clpt.2013.55
[Indexed for MEDLINE]
Free PMC Article
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