Molecular pathology bodies recommend expansion of pharmacogenomic test panels

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The Association for Molecular Pathology (AMP) and other bodies have published recommendations on the inclusion of additional alleles in clinical pharmacogenomic (PGx) genotyping assays.

An AMP working group has developed a series of documents that recommend a minimum set of variants and alleles that laboratories should include in clinical tests of how a patient is likely to respond to certain medicines. In its latest project, the working group investigated clinical CYP3A4 and CYP3A5 PGx testing, leading the AMP and its collaborators to issue consensus recommendations on the genes.

In a statement about the recommendations, Victoria Pratt, chair of the AMP PGx working group and adjunct professor of clinical pharmacology at Indiana University School of Medicine, discussed the decision to focus on the human cytochrome P450 family 3 subfamily A (CYP3A) in the latest document.

“CYP3A serves an important role in the metabolic transformation of approximately 50% of marketed drugs, including fentanyl, midazolam, quetiapine, paclitaxel, statins, and other immunosuppressants,” Pratt said. “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.”

In the consensus document, which was published in The Journal of Molecular Diagnostics, Pratt and her co-authors recommend the inclusion of CYP3A4 and CYP3A5 alleles in either minimum or extended PGx panels.

To be included in the minimum panel, an allele must have a well-characterized effect on the function of the protein or gene expression, an appreciable minor allele frequency, and publicly available reference materials. Alleles must also be technically feasible for clinical laboratories to interrogate using standard molecular testing methods to be included in the minimum panel.

The collaborators identified four CYP3A4 and CYP3A5 alleles for inclusion in minimum panels, as well as one allele that is suitable for inclusion in extended panels. The list of alleles recommended for extended panels is aimed at clinical laboratories that want to offer a more comprehensive genotyping test. Other alleles were not recommended for inclusion in either minimum or extended tests.

“These recommendations are intended to facilitate the design and implementation of pharmacogenomic testing by clinical laboratories,” the authors wrote. “In addition, these recommendations are intended to promote test standardization and improve genotype concordance between clinical laboratories.”

Earlier AMP documents addressed genes important for warfarin PGx testing and the metabolism of other drugs including tamoxifen, opiates, antidepressants, and antipsychotics.

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