Association of carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis with the HLA-B75 serotype or HLA-B*15:21 allele in Filipino patients

Pharmacogenomics J. 2020 Jun;20(3):533-541. doi: 10.1038/s41397-019-0143-8. Epub 2020 Jan 3.

Abstract

A case-control study was conducted to investigate the association of HLA-A alleles, HLA-B alleles including HLA-B*15:02 and HLA-B75 serotype with carbamazepine-induced SJS/TEN in Filipino patients. A retrospective review of medical records was performed. Pertinent clinical data were collected. Eight (8) carbamazepine-induced SJS/TEN cases and 32 tolerant controls were recruited. Genomic DNA was extracted from the saliva samples and genotyping was performed by employing allele-specific polymerase chain reaction. Data were analyzed using the Fisher's exact test, Mann-Whitney U test, univariate logistic regression, and multivariate logistic regression. Single allele association analysis was done. The strength of association was expressed as odds ratio with 95% confidence interval. Positive predictive value, negative predictive value, sensitivity, and specificity were computed. Of all the alleles tested, the HLA-B75 serotype (p = 0.007, OR = 23.25, 95% CI = 2.33-232.21) and HLA-B*15:21 (p = 0.026, OR = 7.53, 95% CI = 1.27-44.79) were significantly associated with carbamazepine-induced SJS/TEN. The HLA-B75 serotype or HLA-B*15:21 allele may be used as a genetic risk assessment prior to prescription for prevention of carbamazepine-induced SJS/TEN in Filipino patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Anticonvulsants / adverse effects*
  • Asian People / genetics*
  • Carbamazepine / adverse effects*
  • Case-Control Studies
  • Female
  • HLA-B Antigens / genetics*
  • Humans
  • Male
  • Middle Aged
  • Philippines / epidemiology
  • Serogroup*
  • Stevens-Johnson Syndrome / epidemiology
  • Stevens-Johnson Syndrome / genetics*
  • Young Adult

Substances

  • Anticonvulsants
  • HLA-B Antigens
  • HLA-B75 antigen
  • Carbamazepine