Document Type


Publication Date



DOI: 10.1038/s41598-021-83570-w; PMCID: PMC7892547


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.

Journal Title

Sci Rep





First Page


Last Page



Grant support

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit

Publisher's Link: