Shih Chi SuChun Bing ChenWan Chun ChangChuang Wei WangWen Lang FanLai Ying LuRyosuke NakamuraYoshiro SaitoMayumi UetaShigeru KinoshitaChonlaphat SukasemKittika YampayonPornpimol KijsanayotinNontaya NakkamNiwat SaksitWichittra TassaneeyakulMichiko AiharaYu Jr LinChee Jen ChangTony WuShuen Iu HungWen Hung ChungUniversity of PhayaoNational Yang-Ming University TaiwanChang Gung Memorial HospitalKyoto Prefectural University of MedicineChulalongkorn UniversityFaculty of Medicine, Khon Kaen UniversityChang Gung UniversityFaculty of Medicine, Ramathibodi Hospital, Mahidol UniversityFaculty of Medicine, Siriraj Hospital, Mahidol UniversityYokohama City University School of MedicineNational Institute of Health Sciences TokyoChang Gung Memorial Hospital2020-01-272020-01-272019-02-01Clinical Pharmacology and Therapeutics. Vol.105, No.2 (2019), 476-48515326535000992362-s2.0-85054192749https://repository.li.mahidol.ac.th/handle/20.500.14594/51938© 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.Mahidol UniversityMedicineArticleSCOPUS10.1002/cpt.1190