Association between HLA-B*1502 and carbamazepine-induced severe cutaneous adverse drug reactions in a Thai population

Epilepsia. 2010 May;51(5):926-30. doi: 10.1111/j.1528-1167.2010.02533.x. Epub 2010 Mar 19.

Abstract

Carbamazepine (CBZ) has been reported as the most common culprit drug for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in several Asian countries including Thailand. A strong association between HLA-B*1502 and CBZ-induced SJS/TEN has been reported in Han Chinese but not in Caucasian and Japanese populations. A case-control study was conducted to determine whether HLA-B*1502 is a valid pharmacogenetic test for SJS/TEN caused by CBZ in a Thai population. Among 42 CBZ-induced patients with SJS/TEN, 37 (88.10%) patients carried the HLA-B*1502 while only 5 (11.90%) of the CBZ-tolerant controls had this allele. The risk of CBZ-induced SJS/TEN was significantly higher in the patients with HLA-B*1502, with an odds ratio (OR) of 54.76 [95% confidence interval (CI) 14.62-205.13, p = 2.89 x 10(-12)]. The sensitivity and specificity of HLA-B*1502 for prediction of CBZ-induced SJS/TEN were 88.10%. By assuming a 0.27% as a prevalence rate of CBZ-induced SJS/TEN in a Thai population, the positive predictive value (PPV) and negative predictive value (NPV) of the HLA-B*1502 were 1.92% and 99.96%. Results from this study suggest that HLA-B*1502 may be a useful pharmacogenetic test for screening Thai individuals who may be at risk for CBZ-induced SJS and TEN.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anticonvulsants / adverse effects*
  • Anticonvulsants / therapeutic use
  • Asian People / genetics
  • Asian People / statistics & numerical data
  • Carbamazepine / adverse effects*
  • Carbamazepine / therapeutic use
  • Child
  • Female
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • HLA-B Antigens / genetics*
  • HLA-B15 Antigen
  • Humans
  • Male
  • Mass Screening / methods
  • Middle Aged
  • Pharmacogenetics
  • Prevalence
  • Risk Factors
  • Stevens-Johnson Syndrome / chemically induced*
  • Stevens-Johnson Syndrome / epidemiology
  • Stevens-Johnson Syndrome / etiology*
  • Stevens-Johnson Syndrome / genetics
  • Thailand / epidemiology
  • Thailand / ethnology

Substances

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