HLA Alleles and CYP2C9*3 as Predictors of Phenytoin Hypersensitivity in East Asians

• Main 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
• Other Authors: University of Phayao
• Format: Article
• Published: 2020
• Subjects: Medicine
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/51938
• Institution: Mahidol University

© 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.