Pharmacogenomic Results

Key Points:

  1. Pharmacogenomic information can play an important role in identifying individuals at risk for reduced therapeutic response or at risk for toxicity when given normal doses of particular medications.
  2. A comprehensive table of medications and their pharmacogenomic biomarker labeling information is available for FDA approved medications.
  3. Gene-drug guidelines to help prescribers with drug selection and dosing can be found at https://cpicpgx.org/

Pharmacogenomic results from exome or whole genome sequencing refer to genetic variants associated with differential responses to medications. These genetic variants may result in variable rates of medication clearance or metabolism. Certain variants may increase a patient’s immune response to a medication. Pharmacogenomic results can alert providers to a patient’s risk for reduced or absent therapeutic response, or to possible toxicity-related adverse events. These can be prevented with medication choice, dose adjustments, or both. Variation within the CYP2C9 gene alters metabolism of many commonly used medications including warfarin and valproic acid. HLA gene variants may cause a patient to have severe adverse reactions when taking certain medications such as carbamazepine.

To learn more about specific gene-drug interactions visit PharmGKB (https://www.pharmgkb.org/).

Example:
The American College of Medical Genetics and Genomics (ACMG) has proposed a list of 56 genes which should be explored as part of secondary analysis when clinical exome or genome sequencing is conducted. One is the RYR1 gene. Some pathogenic variants in RYR1 have been shown to increase susceptibility to malignant hyperthermia when halothane gases, used as a general anesthetic, or succinylcholine, a short-acting muscle relaxant, are administered. Malignant hyperthermia can cause a fast and potentially fatal rise in body temperature and severe muscle contractions. Individuals known to have an increased susceptibility to this reaction because of pathogenic variants in RYR1 should be given alternative medications when undergoing general anesthesia.

Many researchers are studying the return of pharmacogenomic results to the patient’s Electronic Medical Record (EMR) when exome or whole genome sequencing is used. Therefore, clinical sequence data may be analyzed in the relatively near future for important drug response variants associated with professional guidelines or recommendations.

Using pharmacogenomics information to inform medication selection, dosing or both may reduce risk for adverse drug reactions. Consideration of a patient’s other current medications or medical conditions that inhibit or induce genetically normal or differential processes are essential, in addition to consideration of differential drug response due to genetic variants. A comprehensive table of medications and their pharmacogenomic labeling information is available for FDA approved medications: http://www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm083378.htm

 

Next Steps to Consider

  • Consider currently prescribed medications in light of pharmacogenomic results
  • Consult pharmacogenomic results as new medications are being considered and prescribed
  • Explore current knowledge about the specific genetic variant(s) utilizing resources such as CPIC and PharmGKB

 

Resources

  • Clinical Pharmacogenetics Implementation Consortium (CPIC) (http://cpicpgx.org/) - peer-reviewed guidelines for the implementation of pharmacogenomic information into medical practice.
  • PharmGKB (https://www.pharmgkb.org) - a NIH funded pharmacogenomics resource developed by Stanford University that seeks to aid researchers in understanding how genetic variation contributes to differences in drug reactions.
Genomic variation can alter an individual’s response to medication. Phrarmacogenetic test results may indicate a need to alter dosage or selection of an alternative therapeutic.

Genomic variation can alter an individual’s response to medication. Pharmacogenetic test results may indicate a need to alter dosage or selection of an alternative therapeutic.