Association for Molecular Pathology publishes clinical CYP3A4 and CYP3A5 genotyping assay recommendations

July 11, 2023
New joint consensus guideline authored with representatives from AMP, CPIC, CAP, DPWG, ESPT, and PharmGKB builds on previous efforts to standardize testing and enable highest quality healthcare.

The Association for Molecular Pathology (AMP) published consensus recommendations to aid in the design and validation of clinical CYP3A4 and CYP3A5 genotyping assays, promote standardization of testing across different laboratories, and improve patient care. The manuscript, “CYP3A4 and CYP3A5 Genotyping Recommendations: A Joint Consensus Recommendation of the AMP, 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), and Pharmacogenomics Knowledgebase (PharmGKB),” was released online ahead of publication in The Journal of Molecular Diagnostics.

The AMP Pharmacogenetics (PGx) Working Group has developed a series of guidelines designed to help standardize clinical testing for frequently used genotyping assays. The latest report builds on the earlier recommendations for clinical genotyping of TPMT and NUDT15, CYP2C19CYP2C9, CYP2D6, and genes important for warfarin testing. The recommendations should be implemented together with other relevant clinical guidelines, such as those issued by CPIC and DPWG, both of which focus primarily on the interpretation of PGx test results and therapeutic recommendations for specific drug–gene pairs.

The AMP PGx Working Group used the same two-tier categorization of alleles that were recommended for inclusion in the previous clinical PGx genotyping assay guidelines for the latest CYP3A4 and CYP3A5 report. The Tier 1 alleles were selected because they have a well-characterized effect on functional activity, a prevalence of greater than 1% in at least one ancestral subpopulation, and available reference materials for assay validation. The team also defined a Tier 2 list of optional alleles that do not currently meet one or more of the criteria for inclusion in Tier 1. These recommendations are meant to be a reference guide and not to be interpreted as a restrictive list. AMP intends to update these recommendations as new data and/or reference materials become available.

AMP release