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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anticonvulsants / adverse effects*
  • Carbamazepine / adverse effects*
  • Child
  • Child, Preschool
  • Drug Eruptions / etiology
  • Drug Eruptions / genetics
  • Drug Hypersensitivity / etiology
  • Drug Hypersensitivity / genetics*
  • Female
  • Genetic Markers*
  • Genetic Predisposition to Disease
  • Genotyping Techniques
  • HLA-A Antigens / genetics*
  • HLA-B15 Antigen / genetics*
  • Humans
  • Infant
  • Male
  • Stevens-Johnson Syndrome / chemically induced
  • Stevens-Johnson Syndrome / etiology
  • Stevens-Johnson Syndrome / genetics
  • Young Adult

Substances

  • Anticonvulsants
  • Genetic Markers
  • HLA-A Antigens
  • HLA-A*31:01 antigen
  • HLA-B15 Antigen
  • Carbamazepine