Affiliations 

  • 1 Department of Dermatology, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia
  • 2 Faculty of Science, Institute of Biological Sciences, University of Malaya, Kuala Lumpur, Malaysia
  • 3 Allergy and Immunology Research Center, Institute for Medical Research, Kuala Lumpur, Malaysia
  • 4 Department of Dermatology, Hospital Sultanah Aminah, Johor Bahru, Malaysia
  • 5 Pantai Hospital Cheras, Kuala Lumpur, Malaysia
  • 6 Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospitals, Taipei, Taiwan
  • 7 Division of Neurology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
Pharmacogenomics J, 2017 03;17(2):170-173.
PMID: 26927288 DOI: 10.1038/tpj.2016.10

Abstract

Phenytoin (PHT) is a common cause of severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Although HLA-B*15:02 is associated with PHT-induced SJS/TEN (PHT-SJS/TEN) in Han Chinese and Thais, the genetic basis for susceptibility to PHT-induced SCARs (PHT-SCAR) in other populations remains unclear. We performed a case-control association study by genotyping the human leukocyte antigen (HLA)-B alleles of 16 Malay PHT-SCAR patients (13 SJS/TEN and 3 DRESS), 32 PHT-tolerant controls and 300 healthy ethnicity-matched controls. A novel genetic biomarker, HLA-B*15:13, showed significant association with PHT-SJS/TEN (53.8%, 7/13 cases) (odds ratio (OR) 11.28, P=0.003) and PHT-DRESS (100%, 3/3 cases) (OR 59.00, P=0.003) when compared with PHT-tolerant controls (9.4%, 3/32 controls). We also confirmed HLA-B*15:02 association with PHT-SJS/TEN (61.5%, 8/13 cases vs 21.9%, 7/32 controls; OR 5.71, P=0.016) when compared with PHT-tolerant controls. These alleles may serve as markers to predict PHT-SCAR in Malays.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.