title: HLA-A 31:01 and HLA-B 15:02 as genetic markers for carbamazepine hypersensitivity in children.
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.
authors.affiliation: Division of Translational Therapeutics, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: U
authors.initials: U
authors.lastname: Amstutz
authors.forename: C J D
authors.initials: CJ
authors.lastname: Ross
authors.forename: L I
authors.initials: LI
authors.lastname: Castro-Pastrana
authors.forename: M J
authors.initials: MJ
authors.lastname: Rieder
authors.forename: N H
authors.initials: NH
authors.lastname: Shear
authors.forename: M R
authors.initials: MR
authors.lastname: Hayden
authors.forename: B C
authors.initials: BC
authors.lastname: Carleton
mesh_terms: D000293:Adolescent; D000927:Anticonvulsants / Q000009:adverse effects*; D002220:Carbamazepine / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D003875:Drug Eruptions / Q000209:etiology / Q000235:genetics; D004342:Drug Hypersensitivity / Q000209:etiology / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D015234:HLA-A Antigens / Q000235:genetics*; D059910:HLA-B15 Antigen / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D013262:Stevens-Johnson Syndrome / Q000139:chemically induced / Q000209:etiology / Q000235:genetics; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D005819:Genetic Markers; D015234:HLA-A Antigens; C506273:HLA-A*31:01 antigen; D059910:HLA-B15 Antigen; D002220:Carbamazepine