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Warfarin Sensitivity Genotyping in a clinical research laboratory to diagnose the tolerance of the drug warfarin.
The experts have developed a series of guidelines designed to help standardize clinical testing for frequently used genotyping assays and offer the best patient care.

AMP's Clinical Recommendations for CYP3A4 and CYP3A5 Genotyping

New consensus guideline builds on previous efforts to standardize testing and enable highest quality health care

Association for Molecular Pathology
Published:Jul 10, 2023
|2 min read
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ROCKVILLE, MD — The Association for Molecular Pathology (AMP) recently 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 findings were published online 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, CYP2C19, CYP2C9, CYP2D6, and genes important for warfarin testing. The recommendations should be implemented together with other relevant clinical guidelines—such as those issued by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG)—that focus primarily 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 percent of marketed drugs, including fentanyl, midazolam, quetiapine, paclitaxel, statins, and other immunosuppressants,” said Victoria M. Pratt, PhD, chair of the AMP PGx Working Group, director, Scientific Affairs for Pharmacogenetics at Agena Bioscience, and adjunct professor of clinical pharmacology at Indiana University School of Medicine. “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.”

The purpose of recommendations

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 percent 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.

“The full series of AMP Clinical Practice Guidelines and Reports are developed to be of assistance to laboratory and other healthcare professionals by providing guidance and recommendations for particular areas of practice,” said Karen E. Weck, MD, co-chair of the AMP PGx Working Group, director of molecular genetics and pharmacogenomics, and professor of pathology & laboratory medicine and genetics at the University of North Carolina at Chapel Hill. “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.”

- This press release was originally published on the Association for Molecular Pathology website