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

Research output: Contribution to journalArticle

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
JournalClinical Pharmacology and Therapeutics
DOIs
Publication statusAccepted/In press - 01-01-2019

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HLA-B Antigens
Phenytoin
Japan
Alleles
Population
Odds Ratio
Confidence Intervals
ROC Curve
Prescriptions
Case-Control Studies
Genotype
Cytochrome P-450 CYP2C9
Incidence

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

Hikino, Keiko ; Ozeki, Takeshi ; Koido, Masaru ; Terao, Chikashi ; Kamatani, Yoichiro ; Mizukawa, Yoshiko ; Shiohara, Tetsuo ; Tohyama, Mikiko ; Azukizawa, Hiroaki ; Aihara, Michiko ; Nihara, Hiroyuki ; Morita, Eishin ; Murakami, Yoshinori ; Kubo, Michiaki ; Mushiroda, Taisei. / 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. In: Clinical Pharmacology and Therapeutics. 2019.
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title = "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",
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.",
author = "Keiko Hikino and Takeshi Ozeki and Masaru Koido and Chikashi Terao and Yoichiro Kamatani and Yoshiko Mizukawa and Tetsuo Shiohara and Mikiko Tohyama and Hiroaki Azukizawa and Michiko Aihara and Hiroyuki Nihara and Eishin Morita and Yoshinori Murakami and Michiaki Kubo and Taisei Mushiroda",
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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 2019, '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. https://doi.org/10.1002/cpt.1706

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

In: Clinical Pharmacology and Therapeutics, 01.01.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - HLA-B*51:01 and CYP2C9*3 Are Risk Factors for Phenytoin-Induced Eruption in the Japanese Population

T2 - Analysis of Data From the Biobank Japan Project

AU - Hikino, Keiko

AU - Ozeki, Takeshi

AU - Koido, Masaru

AU - Terao, Chikashi

AU - Kamatani, Yoichiro

AU - Mizukawa, Yoshiko

AU - Shiohara, Tetsuo

AU - Tohyama, Mikiko

AU - Azukizawa, Hiroaki

AU - Aihara, Michiko

AU - Nihara, Hiroyuki

AU - Morita, Eishin

AU - Murakami, Yoshinori

AU - Kubo, Michiaki

AU - Mushiroda, Taisei

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

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