Establishment of CYP2D6 Reference Samples by Multiple Validated Genotyping Platforms
| Autor: | Mark J. Ratain, Yusuke Nakamura, Nancy J. Cox, Xiao Liu, Anuar Konkashbaev, Hae Kyung Im, Peter H. O'Donnell, Jacqueline Ramírez, Noura Choudhury, Michiaki Kubo, Hua Fang |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
CYP2D6
Subfamily Genotype Genotyping Techniques Pharmacogenomic Testing Biology Article symbols.namesake Genetics Humans International HapMap Project skin and connective tissue diseases Genotyping Alleles Rank correlation Pharmacology Sanger sequencing pharmacogenomics clinical implementation Genetic Variation Reproducibility of Results sequencing Reference Standards 3. Good health genotyping Cytochrome P-450 CYP2D6 Liver symbols Microsomes Liver Molecular Medicine |
| Zdroj: | The pharmacogenomics journal |
| ISSN: | 1473-1150 1470-269X |
| Popis: | Cytochrome P450 2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6, or 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. |
| Databáze: | OpenAIRE |
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