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.

Keywords::

• Coriell Institute
• cytochrome P450
• Luminex^®
• pharmacogenetic

Disclosure

Tag-It CYP mutation detection reagents and the Caucasian DNA from Coriell that were used to conduct the work presented here were provided by Tm Biosciences. Additional supplies, labor, research design, interpretation and the authoring of this manuscript occured without sponsorship or formal review by Tm Biosciences.