Establishment of CYP2D6 reference samples by multiple validated genotyping platforms

H. Fang, X. Liu, J. Ramírez, N. Choudhury, M. Kubo, H. K. Im, A. Konkashbaev, N. J. Cox, M. J. Ratain, Y. Nakamura, P. H. O'Donnell

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Cytochrome P450 2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6)), a highly polymorphic drug-metabolizing enzyme, is involved in the metabolism of one-quarter of the most commonly prescribed medications. Here we have applied multiple genotyping methods and Sanger sequencing to assign precise and reproducible CYP2D6 genotypes, including copy numbers, for 48 HapMap samples. Furthermore, by analyzing a set of 50 human liver microsomes using endoxifen formation from N-desmethyl-tamoxifen as the phenotype of interest, we observed a significant positive correlation between CYP2D6 genotype-assigned activity score and endoxifen formation rate (rs =0.68 by rank correlation test, P=5.3 × 10-8), which corroborated the genotype-phenotype prediction derived from our genotyping methodologies. In the future, these 48 publicly available HapMap samples characterized by multiple substantiated CYP2D6 genotyping platforms could serve as a reference resource for assay development, validation, quality control and proficiency testing for other CYP2D6 genotyping projects and for programs pursuing clinical pharmacogenomic testing implementation.

Original languageEnglish
Pages (from-to)564-572
Number of pages9
JournalPharmacogenomics Journal
Volume14
Issue number6
DOIs
Publication statusPublished - 11-12-2014

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Pharmacology

Fingerprint Dive into the research topics of 'Establishment of CYP2D6 reference samples by multiple validated genotyping platforms'. Together they form a unique fingerprint.

  • Cite this

    Fang, H., Liu, X., Ramírez, J., Choudhury, N., Kubo, M., Im, H. K., Konkashbaev, A., Cox, N. J., Ratain, M. J., Nakamura, Y., & O'Donnell, P. H. (2014). Establishment of CYP2D6 reference samples by multiple validated genotyping platforms. Pharmacogenomics Journal, 14(6), 564-572. https://doi.org/10.1038/tpj.2014.27