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

U Amstutz1, C J D Ross, L I Castro-Pastrana

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

Clinical Pharmacology and Therapeutics
|April 17, 2013
PubMed

Insights

Genetic markers like HLA-A 31:01 and HLA-B 15:02 predict carbamazepine hypersensitivity in children. HLA-A 31:01 is linked to hypersensitivity syndrome, while HLA-B 15:02 is associated with Stevens-Johnson syndrome.

Area of Science:

  • Pharmacogenomics
  • Immunogenetics
  • Pediatric Adverse Drug Reactions

Background:

  • Carbamazepine (CBZ) use is limited by hypersensitivity reactions, including Stevens-Johnson syndrome (SJS) and drug-induced hypersensitivity syndrome (HSS).
  • Human leukocyte antigen (HLA)-B 15:02 and HLA-A 31:01 are known genetic markers for CBZ hypersensitivity in Asian and European populations.
  • Replication of these associations in diverse pediatric populations is crucial for personalized medicine.

Purpose of the Study:

  • To investigate the association of HLA-A 31:01 and HLA-B 15:02 with CBZ hypersensitivity in pediatric patients from North America.
  • To determine the predictive value of these HLA alleles for specific CBZ-induced hypersensitivity reactions in children.

Main Methods:

  • A case-control study involving 42 pediatric patients with CBZ hypersensitivity and 91 CBZ-tolerant pediatric controls from Canada.
  • Genotyping for HLA-A 31:01 and HLA-B 15:02 alleles was performed using established molecular methods.
  • Statistical analysis, including odds ratio (OR) and P-values, was used to assess the association between HLA alleles and CBZ hypersensitivity phenotypes.

Main Results:

  • HLA-A 31:01 showed a significant association with CBZ-induced hypersensitivity syndrome (HSS) (OR: 26.4, P = 0.0025) and maculopapular exanthema (MPE) (OR: 8.6, P = 0.0037).
  • HLA-B 15:02 was significantly associated with CBZ-induced Stevens-Johnson syndrome (SJS) (OR: 38.6, P = 0.002).
  • Neither HLA-A 31:01 nor HLA-B 15:02 were associated with CBZ-SJS or CBZ-HSS/MPE, respectively.

Conclusions:

  • This study is the first to demonstrate the association of HLA-A 31:01 with CBZ hypersensitivity in pediatric patients.
  • HLA-A 31:01 serves as a significant predictive biomarker for CBZ-HSS and MPE in children across diverse ancestries.
  • HLA-B 15:02 remains a critical predictive marker for CBZ-SJS in pediatric populations.

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