HLA-A*31:01 and HLA-B*15:02 as genetic markers for carbamazepine hypersensitivity in children
نویسندگان
چکیده
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.
منابع مشابه
Exome sequencing pilot study in children with carbamazepine-induced serious skin reactions
Stevens-Johnson syndrome (SJS) and drug-induced hypersensitivity syndrome (HSS, also known as DRESS) are life-threatening drug hypersensitivity reactions. Previous studies on genetic predictors for SJS and HSS were focused on immune-related genes and on known, frequent polymorphisms in the genome. For the anticonvulsant carbamazepine (CBZ), genetic markers for CBZ-induced SJS and HSS have been ...
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BACKGROUND There are 3 classes of HLA molecules; HLA class I, II and III, of which different classes have different functions. HLA-B gene which belongs to HLA class I play an important role predicting drug hypersensitivity. MATERIALS AND METHODS Nine hundred and eighty-six Thai subjects who registered at a pharmacogenomics laboratory were determined for HLA-B genotype using a two-stage sequen...
متن کاملThe HLA-A*31:01 allele: influence on carbamazepine treatment
Carbamazepine (CBZ) is an effective anticonvulsant that can sometimes cause hypersensitivity reactions that vary in frequency and severity. Strong associations have been reported between specific human leukocyte antigen (HLA) alleles and susceptibility to CBZ hypersensitivity reactions. Screening for HLA-B*15:02 is mandated in patients from South East Asia because of a strong association with S...
متن کاملAbs No: HLA-A*31:01 positive hypersensitive patient
Background Hypersensitivity reactions to carbamazepine (CBZ) have been shown to be strongly associated with specific human leukocyte antigen (HLA) alleles, with carriers of the HLA alleles presenting an increased risk of developing hypersensitivity. HLA-B*15:02 was detected in almost all cases of CBZ-induced Stevens-Johnson syndrome (SJS) in patients of Han Chinese or South-East Asian ancestry,...
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