Toward predicting CYP2D6-mediated variable drug response from CYP2D6 gene sequencing data

Science Translational Medicine, vol. 13

Abstract

adjusted = 0.55). Human embryonic kidney cells were used to confirm the effect of five genetic variants on metabolism of the CYP2D6 substrate bufuralol in vitro. These results demonstrate the advantage of a continuous scale and a completely phased genotype for prediction of CYP2D6 enzyme activity and could potentially enable more accurate prediction of individual drug response.

Authors 14

1. Maaike van der Lee Aachen Department of Clinical Pharmacy and Toxicology

   Leiden University Medical Center

   Affiliation as printed

   Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands

   Leiden Network for Personalised Therapeutics, 2333 ZA Leiden, Netherlands

   Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands.; Leiden Network for Personalised Therapeutics, 2333 ZA Leiden, Netherlands

2. William G. Allard Aachen Department of Human Genetics Leiden Genome Technology Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, Netherlands

   Leiden Genome Technology Center, Leiden University Medical Center, 2333 ZA Leiden, Netherlands

3. Rolf H. A. M. Vossen Aachen Department of Human Genetics Leiden Genome Technology Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, Netherlands

   Leiden Genome Technology Center, Leiden University Medical Center, 2333 ZA Leiden, Netherlands

4. Renée F. Baak-Pablo Aachen Department of Clinical Pharmacy and Toxicology

   Leiden University Medical Center

   Affiliation as printed

   Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands

5. Roberta Menafra Aachen Department of Human Genetics Leiden Genome Technology Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, Netherlands

   Leiden Genome Technology Center, Leiden University Medical Center, 2333 ZA Leiden, Netherlands

6. Birgit A. L. M. Deiman

   Catharina Ziekenhuis

   Affiliation as printed

   Clinical Laboratory, Catharina Hospital Eindhoven, 5623 EJ Eindhoven, Netherlands

7. Maarten J. Deenen Aachen Department of Clinical Pharmacy and Toxicology

   Leiden University Medical Center · Catharina Ziekenhuis

   Affiliation as printed

   Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands

   Department of Clinical Pharmacy, Catharina Hospital Eindhoven, 5623 EJ Eindhoven, Netherlands

   Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands.; Department of Clinical Pharmacy, Catharina Hospital Eindhoven, 5623 EJ Eindhoven, Netherlands

8. Patrick Neven

   Universitair Ziekenhuis Leuven

   Affiliation as printed

   University Hospital Leuven, 3000 Leuven, Belgium

9. Inger Johansson

   Karolinska Institutet

   Affiliation as printed

   Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum 5B, 171 77 Solna, Sweden

10. Stefano Gastaldello

    Karolinska Institutet

    Affiliation as printed

    Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum 5B, 171 77 Solna, Sweden

11. Magnus Ingelman‐Sundberg

    Karolinska Institutet

    Affiliation as printed

    Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum 5B, 171 77 Solna, Sweden

12. Henk‐Jan Guchelaar Aachen Department of Clinical Pharmacy and Toxicology

    Leiden University Medical Center

    Affiliation as printed

    Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands

    Leiden Network for Personalised Therapeutics, 2333 ZA Leiden, Netherlands

    Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands.; Leiden Network for Personalised Therapeutics, 2333 ZA Leiden, Netherlands

13. Jesse Joachim Swen corresponding Aachen Department of Clinical Pharmacy and Toxicology

    Leiden University Medical Center

    Affiliation as printed

    Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands

    Leiden Network for Personalised Therapeutics, 2333 ZA Leiden, Netherlands

    Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands.; Leiden Network for Personalised Therapeutics, 2333 ZA Leiden, Netherlands

14. Seyed Yahya Anvar corresponding Aachen Department of Clinical Pharmacy and Toxicology Department of Human Genetics Leiden Genome Technology Center

    Leiden University Medical Center

    Affiliation as printed

    Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands

    Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, Netherlands

    Leiden Genome Technology Center, Leiden University Medical Center, 2333 ZA Leiden, Netherlands

    Leiden Network for Personalised Therapeutics, 2333 ZA Leiden, Netherlands

    Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands.; Leiden Network for Personalised Therapeutics, 2333 ZA Leiden, Netherlands