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

Keiko Hikino, Takeshi Ozeki, Masaru Koido, Chikashi Terao, Yoichiro Kamatani, Yoshiko Mizukawa, Tetsuo Shiohara, Mikiko Tohyama, Hiroaki Azukizawa, Michiko Aihara, Hiroyuki Nihara, Eishin Morita, Yoshinori Murakami, Michiaki Kubo, Taisei Mushiroda

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Abstract

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.

Original languageEnglish
Pages (from-to)1170-1178
Number of pages9
JournalClinical Pharmacology and Therapeutics
Volume107
Issue number5
DOIs
Publication statusPublished - 01-05-2020

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

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    Hikino, K., Ozeki, T., Koido, M., Terao, C., Kamatani, Y., Mizukawa, Y., Shiohara, T., Tohyama, M., Azukizawa, H., Aihara, M., Nihara, H., Morita, E., Murakami, Y., Kubo, M., & Mushiroda, T. (2020). 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. Clinical Pharmacology and Therapeutics, 107(5), 1170-1178. https://doi.org/10.1002/cpt.1706