Association for Molecular Pathology publishes recommendations to facilitate design and implementation of clinical pharmacogenomic DPYD genotyping assays
The Association for Molecular Pathology (AMP) published consensus recommendations to aid in the design and validation of clinical DPYD genotyping assays, promote standardization of testing across different laboratories, and improve patient care.
The manuscript, “DPYD Genotyping Recommendations: A Joint Consensus Recommendation of the AMP, American College of Medical Genetics and Genomics (ACMG), Clinical Pharmacogenetics Implementation Consortium (CPIC), College of American Pathologists (CAP), Dutch Pharmacogenetics Working Group (DPWG) of the Royal Dutch Pharmacists Association, European Society for Pharmacogenomics and Personalized Therapy (ESPT), Pharmacogenomics Knowledgebase (PharmGKB), and Pharmacogene Variation Consortium (PharmVar),” was released online ahead of publication in The Journal of Molecular Diagnostics.
The AMP Clinical Practice Committee’s Pharmacogenomics (PGx) Working Group was established to define the key attributes of pharmacogenetic alleles recommended for clinical testing, along with a minimum set of variants that should be included in clinical PGx genotyping assays. The new DPYD report is the latest in a series of recommendations developed by the AMP PGx Working Group to help standardize clinical testing for frequently used genotyping assays. It builds on the earlier clinical genotyping recommendations for CYP3A4/CYP3A5, TPMT/NUDT15, CYP2D6, genes important for warfarin testing, CYP2C9, and CYP2C19. It is important for healthcare providers to implement the recommendations along with other relevant clinical guidelines, such as those issued by CPIC and DPWG, both of which have a primary focus on interpreting PGx test results and providing therapeutic recommendations for specific drug-gene pairs.
The AMP PGx Working Group used a two-tier categorization of variants recommended for inclusion, as with previous clinical PGx genotyping assay recommendations. The Tier 1 recommended variants were selected because they have a well-characterized effect on functional activity of the protein and/or gene expression, have an appreciable minor allele frequency in a population/ancestral group, have available reference materials for assay validation, and are technically feasible for clinical laboratories to interrogate using standard molecular testing methods. The Tier 2 list of optional variants meet at least one, but not all, of the Tier 1 criteria. These recommendations for clinical genotyping assays do not include variants with an unknown effect on protein function or gene expression. They are meant to be a reference guide and not a restrictive list.
