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 language | English |
|---|---|
| Journal | Clinical Pharmacology and Therapeutics |
| DOIs | |
| Publication status | Accepted/In press - 01-01-2019 |
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All Science Journal Classification (ASJC) codes
- Pharmacology
- Pharmacology (medical)
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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 journal › Article
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.
AB - 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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U2 - 10.1002/cpt.1706
DO - 10.1002/cpt.1706
M3 - Article
C2 - 31646624
AN - SCOPUS:85076369057
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
SN - 0009-9236
ER -