Establishment of CYP2D6 reference samples by multiple validated genotyping platforms

Pharmacogenomics J. 2014 Dec;14(6):564-72. doi: 10.1038/tpj.2014.27. Epub 2014 Jul 1.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Cytochrome P-450 CYP2D6 / genetics*
  • Genetic Variation / genetics
  • Genotype
  • Genotyping Techniques / standards*
  • Humans
  • Liver / cytology
  • Liver / enzymology
  • Microsomes, Liver / enzymology
  • Reference Standards
  • Reproducibility of Results


  • Cytochrome P-450 CYP2D6