Establishment of CYP2D6 reference samples by multiple validated genotyping platforms.

摘要: 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 most commonly prescribed medications. Here we have applied multiple genotyping methods and Sanger sequencing to assign precise reproducible CYP2D6 genotypes, including copy numbers, for 48 HapMap samples. Furthermore, by analyzing set 50 human liver microsomes using endoxifen formation from N-desmethyl-tamoxifen as phenotype interest, observed significant positive correlation between genotype-assigned activity score rate (rs=0.68 rank test, P=5.3 × 10−8), which corroborated genotype–phenotype prediction derived our methodologies. In future, these publicly available samples characterized substantiated platforms could serve reference resource assay development, validation, quality control proficiency testing other projects programs pursuing clinical pharmacogenomic implementation.