title: Determination of CYP2D6, CYP2C9 and CYP2C19 genotypes with Tag-It mutation detection assays.
abstract: Cytochrome P450 (CYP) genotyping can be used to prospectively identify individuals at risk for adverse drug reactions or therapeutic failure due to altered drug metabolism. Based on the specific CYP(s) affected, individuals may require less or more of a particular drug than people with unaffected CYP-mediated metabolism, or may be best managed by avoiding certain drugs entirely. Here we evaluated the Tag-It CYP mutation detection reagents (Tm Bioscience Corp.). As these reagents, based on a universal bead array, detect more than 20 clinically significant variants common to different ancestries, it was important to consider DNA from genetically diverse populations. Thus, we also report CYP2D6, CYP2C9 and CYP2C19 genotypes for DNA available through the Coriell Institute for Medical Research (NJ, USA). These samples represent individuals from Caucasian, Japanese, Chinese, Southeast Asian, African-American and Middle Eastern ancestry, and provide an excellent resource for evaluating and validating CYP genotyping methods. Using these samples, the Tag-It mutation detections assays reliably provided genotypes for CYP2D6, CYP2C9 and CYP2C19. The CYP2C9 and CYP2C19 assays were particularly robust and were easily implemented in our clinical laboratory. The CYP2D6 assay was somewhat less robust and could be improved by associating the 2850C>T variant with a specific allele, as well as by discriminating the allele affected when gene duplication is detected.
authors.affiliation: ARUP Institute for Experimental and Clinical Pathology, 500 Chipeta Way, Salt Lake City, UT 84108, USA.
authors.forename: Roberta
authors.initials: R
authors.lastname: Melis
authors.forename: Elaine
authors.initials: E
authors.lastname: Lyon
authors.forename: Gwendolyn A
authors.initials: GA
authors.lastname: McMillin
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis / Q000191:economics / Q000379:methods*; D005838:Genotype; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D012680:Sensitivity and Specificity
chemical_list: D004247:DNA; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6