HLA-B51:01 and CYP2C93 Are Risk Factors for Phenytoin-Induced Eruption in the Japanese Population: Analysis of Data From the Biobank Japan Project

被引：12

作者：

Hikino, Keiko ^{[1
]}

Ozeki, Takeshi ^{[1
]}

Koido, Masaru ^{[2
]}

Terao, Chikashi ^{[2
]}

Kamatani, Yoichiro ^{[2
,3
]}

Mizukawa, Yoshiko ^{[4
]}

Shiohara, Tetsuo ^{[4
]}

Tohyama, Mikiko ^{[5
]}

Azukizawa, Hiroaki ^{[6
]}

Aihara, Michiko ^{[7
]}

Nihara, Hiroyuki ^{[8
]}

Morita, Eishin ^{[8
]}

Murakami, Yoshinori ^{[9
]}

Kubo, Michiaki ^{[10
]}

Mushiroda, Taisei ^{[1
]}

机构：

[1] RIKEN, Lab Pharmacogen, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan

[2] RIKEN, Lab Stat & Translat Genet, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan

[3] Univ Tokyo, Grad Sch Frontier Sci, Lab Complex Trait Genom, Tokyo, Japan

[4] Kyorin Univ, Dept Dermatol, Sch Med, Tokyo, Japan

[5] Ehime Univ, Dept Dermatol, Grad Sch Med, Matsuyama, Ehime, Japan

[6] Osaka Univ, Grad Sch Med, Dept Dermatol, Osaka, Japan

[7] Yokohama City Univ, Dept Environm Immunodermatol, Grad Sch Med, Yokohama, Kanagawa, Japan

[8] Shimane Univ, Dept Dermatol, Fac Med, Matsue, Shimane, Japan

[9] Univ Tokyo, Inst Med Sci, Div Mol Pathol, Tokyo, Japan

[10] RIKEN, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan

来源：

CLINICAL PHARMACOLOGY & THERAPEUTICS | 2020年 / 107卷 / 05期

关键词：

STEVENS-JOHNSON-SYNDROME; TOXIC EPIDERMAL NECROLYSIS; GENOME-WIDE ASSOCIATION; HLA-B; CYP2C9; LOCI; PHARMACOGENETICS; VARIANTS; THERAPY; DESIGN;

D O I：

10.1002/cpt.1706

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：1170 / 1178

页数：9

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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

HLA-B51:01 and CYP2C93 Are Risk Factors for Phenytoin-Induced Eruption in the Japanese Population: Analysis of Data From the Biobank Japan Project