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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/61899
Title: Relationship between CYP2D6 genotype, activity score and phenotype in a pediatric Thai population treated with risperidone
Authors: Yaowaluck Hongkaew
Andrea Gaedigk
Bob Wilffert
Nattawat Ngamsamut
Wiranpat Kittitharaphan
Penkhae Limsila
Chonlaphat Sukasem
Ramathibodi Hospital
Bumrungrad International Hospital
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Thailand Ministry of Public Health
University of Groningen
University of Missouri-Kansas City
University of Groningen, University Medical Center Groningen
Division of Clinical Pharmacology, Toxicology and Therapeutic Innovation
Keywords: Multidisciplinary
Issue Date: 1-Dec-2021
Citation: Scientific Reports. Vol.11, No.1 (2021)
Abstract: © 2021, The Author(s). Recently, the Clinical Pharmacogenetics Implementation Consortium (CPIC) have revised recommendations for the translation of CYP2D6 genotype to phenotype. Changes affect phenotype grouping, as well as the value used to calculate activity score for the CYP2D6*10 allele to better reflect the substantially decreased activity of this allele which is the most frequent allele found in Asian populations. This study aimed to evaluate whether the lower value for CYP2D6*10 as recommended, and the revised phenotype groupings improve the relationship between CYP2D6 genotype and risperidone measures. One hundred and ninety-nine children and adolescents with autism treated with a risperidone-based regimen for at least four weeks were included. CYP2D6 genotype was determined using the Luminex xTAG CYP2D6 Kit assay and translated into phenotype using different translation methods. Plasma concentrations of risperidone and 9-hydroxyrisperidone were measured using LC/MS/MS. Plasma levels of risperidone, risperidone concentration/dose ratio, and risperidone/9-hydroxyrisperidone ratio in patients with an activity score < 1 were significantly higher than those ≥ 1 (P value < 0.001 for all three parameters). Plasma risperidone levels and risperidone concentration/dose ratios were significantly higher in intermediate metabolizers (defined as AS = 0.25–0.75) than normal metabolizer (defined as AS = 1–2) patients (1.44 vs. 0.23 ng/ml, P < 0.001 and 1.63 vs. 0.29 ng/ml/ng, P < 0.001, respectively) as well as risperidone/9-hydroxyrisperidone ratio (0.20 vs. 0.04, P < 0.001). This is the first study in an Asian population utilizing the revised CPIC-recommended method for translating the CYP2D6 genotype to phenotype. In addition to validating that CYP2D6 genetic variation significantly impacts risperidone metabolism, we demonstrated that revised value for the CYP2D6*10 was superior for genotype to phenotype translation. However, at least for risperidone, subjects with an activity score of 1 presented as phenotypic normal, and not intermediate metabolizers, suggesting that phenotype classification is substrate dependent.
URI: http://repository.li.mahidol.ac.th/dspace/handle/123456789/61899
metadata.dc.identifier.url: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85101212032&origin=inward
ISSN: 20452322
Appears in Collections:Scopus 2021

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