HLA-B*51:01 and CYP2C9*3 Are Risk Factors for Phenytoin-Induced Eruption in the Japanese Population: Analysis of Data From the Biobank Japan Project

Clin Pharmacol Ther. 2020 May;107(5):1170-1178. doi: 10.1002/cpt.1706. Epub 2019 Dec 6.


CYP2C9*3 and HLA-B alleles are reportedly associated with phenytoin-induced eruption in some East Asian populations; however, this finding is not readily applicable to the Japanese population. Thus, we aimed to investigate the risk alleles using samples and data from BioBank Japan. A total of 747 patients (24 cases and 723 tolerant controls) were selected for analysis. Case-control association studies were conducted, using CYP2C9*3, CYP2C9*27, CYP2C19*2, CYP2C19*3, and HLA-B allele genotype data. CYP2C9*3 carrier status was significantly associated with phenytoin-induced eruption (P = 0.0022, odds ratio 7.05, 95% confidence interval, 2.44-20.4). HLA-B*51:01 showed the most prominent association (P = 0.010, odds ratio 3.19, 95% confidence interval, 1.37-7.48). Including both of these features improved predictive performance, measured as area under the receiver operating characteristic curve, by 10%. CYP2C9*3 and HLA-B*51:01 allele carrier statuses are significantly associated with phenytoin-induced eruption; thus, checking this carrier status before prescription would decrease the incidence of phenytoin-induced eruption in clinical practice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Anticonvulsants / adverse effects*
  • Asian Continental Ancestry Group / genetics
  • Biological Specimen Banks
  • Case-Control Studies
  • Child
  • Cytochrome P-450 CYP2C9 / genetics*
  • Drug Eruptions / etiology*
  • Drug Eruptions / genetics
  • Female
  • Genotype
  • HLA-B51 Antigen / genetics*
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Phenytoin / adverse effects*
  • Retrospective Studies
  • Risk Factors
  • Young Adult


  • Anticonvulsants
  • HLA-B51 Antigen
  • Phenytoin
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9