engleski

CYP2D6 revisited in GENDEP: inter-platform concordance

Background: Despite guidelines indicating potential clinical utility of genotyping for CYP2D6, this is not yet routinely provided. A contributing factor to this is the complexity of the locus including “structural variants” (complete or partial gene deletions and duplications). Methods: Samples with a variety of CYP2D6 genotypes according to prior data were selected from the Genome-based therapeutic drugs for depression (GENDEP) study (Huezo-Diaz et al., 2012) and subjected to TaqMan copy number variant (CNV) analysis using probes specific for different CYP2D6 regions, to the Ion S5 AmpliSeq Pharmacogenomics Panel and to PharmacoScan Solution. Translator files were written to facilitate data interpretation. Results: For samples of a CNV call of two across TaqMan or PharmacoScan CNV probes, the concordance between IonS5 and PharmacoScan was 94% (32/34), with the two nonconcordant samples having variants detected by Pharmaco- Scan that are not currently in the IonS5 panel (CYP2D6*22 and CYP2D6*25). For samples with a CNV call of one across the probes, there was 100% concordance between the two platforms. For samples with a CNV call of 3 across TaqMan or PharmacoScan CNV probes, the concordance was 94% (16/17). Concordance was less for samples with unequal call across the probes, consistent with hybrid alleles. Conclusions: The Ion S5 AmpliSeq data show a high rate of concordance with PharmacoScan solution for all types of CYP2D6 variants apart from the hybrid variants (found at 2%, 18/859 in GENDEP).

antidepressant ; CYP2D6 ; CYP2C19 ; pharmacogenomics

nije evidentirano