AMP Releases CYP3A4 and CYP3A5 Genotyping Assay Recommendations

The Association for Molecular Pathology (AMP), the world’s leading professional society for molecular diagnostics, released consensus recommendations today to aid in the design and validation of clinical CYP3A4 and CYP3A5 genotyping assays, encourage standardization of testing across labs, and better patient care.

The study was published in The Journal of Molecular Diagnostics.

The AMP Pharmacogenetics (PGx) Working Group has created a set of guidelines to aid in the standardization of clinical testing for commonly used genotyping assays. The recent report expands on the previous recommendations for clinical genotyping of TPMT and NUDT15, CYP2C19, CYP2C9, CYP2D6, and genes essential for warfarin testing.

The suggestions should be made in conjunction with other relevant clinical guidelines, like those released by CPIC and DPWG, which both concentrate on the interpretation of PGx test results and therapeutic recommendations for specific drug-gene pairs.

The human cytochrome P450 family 3 subfamily A (CYP3A) serves an important role in the metabolic transformation of approximately 50% of marketed drugs, including fentanyl, midazolam, quetiapine, paclitaxel, statins, and other immunosuppressants.”

Victoria M. Pratt PhD, Chair, AMP PGx Working Group

Victoria M. Pratt is also the Director of Scientific Affairs for Pharmacogenetics at Agena Bioscience and Adjunct Professor of Clinical Pharmacology at Indiana University School of Medicine.

Victoria M. Pratt adds, “As the molecular diagnostic landscape evolves, AMP is committed to sharing our expertise and collaborating with the broader laboratory community to continuously improve professional PGx practices for CYP3A4 and CYP3A5, as well as many other common genotyping assays.”

For the latest CYP3A4 and CYP3A5 report, the AMP PGx Working Group used the same two-tier categorization of alleles that was suggested for inclusion in the earlier clinical PGx genotyping assay guidelines.

Tier 1 alleles were chosen since they have a well-characterized impact on functional activity, an incidence of more than 1% in at least one ancestral subpopulation, and reference materials for assay validation. The team also established a Tier 2 list of optional alleles that do not currently meet one or more of the Tier 1 criteria.

These suggestions are meant to serve as a reference guide, not as a restrictive list. As new data and/or reference materials become available, AMP aims to update these recommendations.

The full series of AMP Clinical Practice Guidelines and Reports are developed to be of assistance to laboratory and other health care professionals by providing guidance and recommendations for particular areas of practice. The AMP PGx Working Group was established to help standardize clinical testing across laboratories, ensure the assays investigate the most clinically relevant variant alleles, and enable healthcare professionals to provide high-quality patient care.”

Karen E. Weck MD, Co-Chair, AMP PGx Working Group

Karen E. Weck is also the Director of Molecular Genetics and Pharmacogenomics and Professor of Pathology & Laboratory Medicine and Genetics at the University of North Carolina at Chapel Hill.