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Title: HLA Alleles and CYP2C9*3 as Predictors of Phenytoin Hypersensitivity in East Asians
Authors: Shih Chi Su
Chun Bing Chen
Wan Chun Chang
Chuang Wei Wang
Wen Lang Fan
Lai Ying Lu
Ryosuke Nakamura
Yoshiro Saito
Mayumi Ueta
Shigeru Kinoshita
Chonlaphat Sukasem
Kittika Yampayon
Pornpimol Kijsanayotin
Nontaya Nakkam
Niwat Saksit
Wichittra Tassaneeyakul
Michiko Aihara
Yu Jr Lin
Chee Jen Chang
Tony Wu
Shuen Iu Hung
Wen Hung Chung
University of Phayao
National Yang-Ming University Taiwan
Chang Gung Memorial Hospital
Kyoto Prefectural University of Medicine
Chulalongkorn University
Faculty of Medicine, Khon Kaen University
Chang Gung University
Faculty of Medicine, Ramathibodi Hospital, Mahidol University
Faculty of Medicine, Siriraj Hospital, Mahidol University
Yokohama City University School of Medicine
National Institute of Health Sciences Tokyo
Chang Gung Memorial Hospital
Keywords: Medicine
Issue Date: 1-Feb-2019
Citation: Clinical Pharmacology and Therapeutics. Vol.105, No.2 (2019), 476-485
Abstract: © 2018 American Society for Clinical Pharmacology and Therapeutics To develop a pre-emptive genetic test that comprises multiple predisposing alleles for the prevention of phenytoin-related severe cutaneous adverse reactions (SCARs), three sets of patients with phenytoin-SCAR and drug-tolerant controls from Taiwan, Thailand, and Japan, were enrolled for this study. In addition to cytochrome P450 (CYP)2C9*3, we found that HLA-B*13:01, HLA-B*15:02, and HLA-B*51:01 were significantly associated with phenytoin hypersensitivity with distinct phenotypic specificities. Strikingly, we showed an increase in predictive sensitivity of concurrently testing CYP2C9*3/HLA-B*13:01/HLA-B*15:02/HLA-B*51:01 from 30.5–71.9% for selecting the individuals with the risk of developing phenytoin-SCAR in Taiwanese cohorts, accompanied by a specificity of 77.7% (combined sensitivity, 64.7%; specificity, 71.9% for three Asian populations). Meta-analysis of the four combined risk alleles showed significant associations with phenytoin-SCAR in three Asian populations. In conclusion, combining the assessment of risk alleles of HLA and CYP2C9 potentiated the usefulness of predictive genetic tests to prevent phenytoin hypersensitivity in Asians.
ISSN: 15326535
Appears in Collections:Scopus 2019

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