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Clin Pharmacol Ther. 2019 Oct 23. doi: 10.1002/cpt.1706. [Epub ahead of print]

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.

Author information

1
Laboratory for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences, Yokohama City, Kanagawa, Japan.
2
Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama City, Kanagawa, Japan.
3
Laboratory of Complex Trait Genomics, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
4
Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan.
5
Department of Dermatology, Ehime University Graduate School of Medicine, Ehime, Japan.
6
Department of Dermatology, Osaka University Graduate School of Medicine, Osaka, Japan.
7
Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
8
Department of Dermatology, Faculty of Medicine, Shimane University, Shimane, Japan.
9
Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
10
RIKEN Center for Integrative Medical Sciences, Yokohama City, Kanagawa, Japan.

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.

PMID:
31646624
DOI:
10.1002/cpt.1706

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