Association of HLA-B*1502 allele with carbamazepine-induced toxic epidermal necrolysis and Stevens-Johnson syndrome in the multi-ethnic Malaysian population

Int J Dermatol. 2011 Feb;50(2):221-4. doi: 10.1111/j.1365-4632.2010.04745.x.

Abstract

Background: Carbamazepine (CBZ), a frequently used anticonvulsant drug, is one of the most common causes of life-threatening cutaneous adverse drug reactions such as toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS). Recent studies have revealed a strong association between HLA-B*1502 and CBZ-induced TEN/SJS in the Taiwan Han Chinese population.

Objectives: This study is aimed to investigate the association between human leucocyte antigens (HLA) and CBZ-induced TEN/SJS in the multi-ethnic Malaysian population.

Methods: A sample of 21 unrelated patients with CBZ-induced TEN/SJS and 300 race-matched, healthy controls were genotyped for HLA-A, -B and -DR using polymerase chain reaction (PCR). Allele frequencies were compared.

Results: HLA-B*1502 was present in 75.0% (12/16) of Malay patients with CBZ-induced TEN/SJS but in only 15.7% (47/300) of normal controls (odds ratio 16.15, 95% confidence interval 4.57-62.4; corrected P-value = 7.87 × 10(-6) ), which suggests a strong association between HLA and CBZ-induced TEN/SJS. Additionally, HLA-B*1502 was found in all three Chinese and two Indian patients. Existing data show that frequencies of the HLA-B*1502 allele are generally much higher in Asian populations than in White European populations, which explains the higher incidences of SJS and TEN in Asian countries.

Conclusions: HLA-B*1502 is strongly associated with CBZ-induced TEN/SJS in the Malay population in Malaysia, as has been seen in Han Chinese in Taiwan. This indicates that the genetic association apparent in the incidence of CBZ-induced TEN/SJS is linked with the presence of HLA-B*1502, irrespective of racial origin. Screening of patients for this genetic marker can help to prevent the occurrence of TEN/SJS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticonvulsants / adverse effects*
  • Asian People / genetics
  • Carbamazepine / adverse effects*
  • Genetic Markers
  • Genetic Predisposition to Disease
  • HLA-B Antigens / genetics*
  • HLA-B15 Antigen
  • Humans
  • Incidence
  • Malaysia / epidemiology
  • Stevens-Johnson Syndrome / chemically induced*
  • Stevens-Johnson Syndrome / epidemiology
  • Stevens-Johnson Syndrome / etiology
  • Stevens-Johnson Syndrome / genetics*

Substances

  • Anticonvulsants
  • Genetic Markers
  • HLA-B Antigens
  • HLA-B*15:02 antigen
  • HLA-B15 Antigen
  • Carbamazepine