Pharmacogenetics for Healthcare Professionals

This website is intended to help healthcare professionals understand select pharmacogenetic test results using available FDA label information and independent clinical guidelines* published in peer-reviewed journals.

This information is for reference only and has not been reviewed by the FDA. This information does not constitute medical advice and does not take the place of routine clinical monitoring. Clinicians should use professional judgment in the interpretation of any clinical recommendations.

CYP2C19

The CYP2C19 gene encodes the CYP2C19 enzyme, which helps metabolize many commonly used medications, such as proton pump inhibitors, the antiplatelet clopidogrel, and certain antidepressants.

Guideline Overviews and Relevant FDA Label Information

DPYD

The DPYD gene encodes the DPD enzyme, which helps break down fluoropyrimidine chemotherapy medications, including fluorouracil (5-FU) and capecitabine.

Guideline Overviews and Relevant FDA Label Information

SLCO1B1

The SLCO1B1 gene encodes the SLCO1B1 protein, which helps transport cholesterol-lowering statins into the liver for removal from the body.

Guideline Overviews and Relevant FDA Label Information

*The guidelines referenced herein reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time these guidelines were written and are intended only to assist clinicians in decision making and to identify questions for further research. New evidence may have emerged since the time a guideline was submitted for publication. Guidelines are limited in scope and are not applicable to interventions or diseases that are not specifically identified. Guidelines do not account for individual variations among patients and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the healthcare provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient.

Please refer to cpicpgx.org or pharmgkb.org to access the most current guideline content.

Common Questions About 23andMe’s Pharmacogenetics Reports

What are the 23andMe Pharmacogenetics reports?

23andMe Pharmacogenetics reports* provide information about DNA variants that may influence the body’s ability to process certain medications. Having a variant means that some medications may be processed faster or slower than normal, which, depending on the medication, may reduce effectiveness or increase the chance of experiencing side effects. However, most medications won’t be affected by having these DNA variants.

23andMe Pharmacogenetics reports are intended to provide genetic information that may aid discussions between consumers and healthcare professionals about therapeutic options. Results from 23andMe Pharmacogenetics reports should not be used to make medical decisions and should be confirmed in a clinical setting with independent genetic testing before taking any medical action.

Currently, 23andMe provides three Pharmacogenetics reports to customers: CYP2C19 Drug Metabolism, DPYD Drug Metabolism, and SLCO1B1 Drug Transport.

*The 23andMe Personal Genome Service (PGS) is a qualitative genotyping assessment system applied to genomic DNA isolated from human saliva to simultaneously detect, report, and interpret genetic variants in a broad multigene test. The 23andMe PGS Pharmacogenetics reports provide and interpret genetic information about the processing of certain therapeutics to inform discussions with a healthcare professional. They do not describe if a person will or will not respond to a particular therapeutic and do not describe the association between detected variants and any specific therapeutic. Results should be confirmed in a clinical setting with independent genetic testing before taking any medical action. Warning: Test information should not be used to start, stop, or change any course of treatment and does not test for all possible variants that may affect metabolism or protein function. The PGS test is not a substitute for visits to a healthcare professional. Making changes to a drug regimen can lead to harmful side effects or reduce intended benefits of the medication, therefore consult with a healthcare professional before taking any medical action. For more information, visit 23andme.com/test-info/.

What are the limitations of the 23andMe Pharmacogenetics reports?

The 23andMe Pharmacogenetics reports:

  • Do not test for all possible DNA variants in the CYP2C19, DPYD, or SLCO1B1 genes that may affect enzyme metabolism or protein function.
  • Do not test for DNA variants in other genes that may affect other proteins involved in the processing of medications.
  • Do not provide information on associations between specific DNA variants and any specific medications.
  • Do not account for lifestyle or other health factors that may affect individual processing of medications.
  • Should not be used to make medical decisions. Results should be confirmed in a clinical setting with independent genetic testing before taking any medical action.

How can this web portal help healthcare professionals better understand the 23andMe Pharmacogenetics reports?

The 23andMe Pharmacogenetics reports are intended to provide genetic information that may aid discussions between consumers and healthcare professionals about therapeutic options. This portal provides overviews of peer-reviewed pharmacogenetic guidelines and relevant FDA-approved drug labels that may enhance these discussions. The guideline recommendations included from the Clinical Pharmacogenetics Implementation Consortium(CPIC®) are rated by CPIC as “strong” unless otherwise noted.

It’s important to note that pharmacogenetic guidelines are optional and are intended for reference only, as many other factors besides genetics are considered in clinical decision-making. Pharmacogenetic information may be most helpful before treatment has begun, but it may also provide insights into some cases of non-response or unexpected side effects once therapy is underway. Patients who are already on a stable dose of medication that is working well may be less likely to benefit from dosing changes based on genetic information. Clinicians should use professional judgment in the interpretation of pharmacogenetic information and clinical guidelines.

Where can healthcare professionals find a lab to order confirmatory testing?

The Genetic Testing Registry (GTR®) provides a central location for genetic test providers to describe their test offerings, including pharmacogenetic tests.

Website: ncbi.nlm.nih.gov/gtr/

GTR® is hosted by the National Center for Biotechnology Information (NCBI), which is funded by the National Institutes of Health (NIH).

How can this web portal help healthcare professionals better understand the 23andMe Pharmacogenetics reports?

The 23andMe Pharmacogenetics reports are intended to provide genetic information that may aid discussions between consumers and healthcare professionals about therapeutic options. This portal provides overviews of peer-reviewed pharmacogenetic guidelines and relevant FDA-approved drug labels that may enhance these discussions. The guideline recommendations included from the Clinical Pharmacogenetics Implementation Consortium(CPIC®) are rated by CPIC as “strong” unless otherwise noted.

It’s important to note that pharmacogenetic guidelines are optional and are intended for reference only, as many other factors besides genetics are considered in clinical decision-making. Pharmacogenetic information may be most helpful before treatment has begun, but it may also provide insights into some cases of non-response or unexpected side effects once therapy is underway. Patients who are already on a stable dose of medication that is working well may be less likely to benefit from dosing changes based on genetic information. Clinicians should use professional judgment in the interpretation of pharmacogenetic information and clinical guidelines.

How accurate are the 23andMe Pharmacogenetics reports?

23andMe Pharmacogenetics reports have been authorized by the FDA and meet similar FDA standards of clinical and analytical validity as the 23andMe Carrier Status* and Genetic Health Risk* reports. All saliva samples are processed in CLIA-certified and CAP-accredited labs and are genotyped using a custom version of the Illumina Global Screening Array (GSA).

Accuracy was determined by comparing results from the 23andMe genotyping array with results from Sanger sequencing. Greater than 99% of test results were correct. While unlikely, the 23andMe Pharmacogenetics test may provide false positive or false negative results.

*The 23andMe PGS test uses qualitative genotyping to detect select clinically relevant variants in the genomic DNA of adults from saliva for the purpose of reporting and interpreting genetic health risks and reporting carrier status. It is not intended to diagnose any disease. Your ethnicity may affect the relevance of each report and how your genetic health risk results are interpreted. Each genetic health risk report describes if a person has variants associated with a higher risk of developing a disease, but does not describe a person’s overall risk of developing the disease. The test is not intended to tell you anything about your current state of health, or to be used to make medical decisions, including whether or not you should take a medication, how much of a medication you should take, or determine any treatment. Our carrier status reports can be used to determine carrier status, but cannot determine if you have two copies of any genetic variant. These carrier reports are not intended to tell you anything about your risk for developing a disease in the future, the health of your fetus, or your newborn child’s risk of developing a particular disease later in life. For certain conditions, we provide a single report that includes information on both carrier status and genetic health risk. Warnings & Limitations: The 23andMe PGS Genetic Health Risk Report for BRCA1/BRCA2 (Selected Variants) is indicated for reporting of the 185delAG and 5382insC variants in the BRCA1 gene and the 6174delT variant in the BRCA2 gene. The report describes if a woman is at increased risk of developing breast and ovarian cancer, and if a man is at increased risk of developing breast cancer or may be at increased risk of developing prostate cancer. The three variants included in this report are most common in people of Ashkenazi Jewish descent and do not represent the majority of BRCA1/BRCA2 variants in the general population. This report does not include variants in other genes linked to hereditary cancers and the absence of variants included in this report does not rule out the presence of other genetic variants that may impact cancer risk. The PGS test is not a substitute for visits to a healthcare professional for recommended screenings or appropriate follow-up. Results should be confirmed in a clinical setting before taking any medical action. For important information and limitations regarding each genetic health risk and carrier status report, visit 23andme.com/test-info/.

Common Questions about Pharmacogenetics

What other resources are available for learning about pharmacogenetics?

What is DPWG?

The Dutch Pharmacogenetics Working Group (DPWG) is a collaboration between pharmacists, physicians, clinical pharmacologists, chemists, and others to develop therapeutic recommendations based on pharmacogenetic information and to help healthcare professionals integrate this information into their clinical practice. The DPWG was founded in 2005 by the Royal Dutch Pharmacist’s Association.

What is PharmGKB?

The PharmGKB is a pharmacogenomics knowledge resource that encompasses clinical information including clinical guidelines and drug labels, potentially clinically actionable gene-drug associations, and genotype-phenotype relationships. PharmGKB collects, curates, and disseminates knowledge about the impact of human genetic variation on drug responses.

Website: pharmgkb.org

What is CPIC®?

CPIC® stands for the Clinical Pharmacogenetics Implementation Consortium. CPIC® is an international consortium of clinicians and researchers that helps facilitate the use of pharmacogenetic information for patient care. CPIC evaluates the available clinical evidence supporting gene-drug pairs and publishes genotype-based dosing guidelines to help healthcare professionals interpret genetic information for use in their prescribing practices.

Website: cpicpgx.org

What is “pharmacogenetics” and how do DNA variants affect the processing of medications?

The field of pharmacogenetics explores how DNA variants influence the body’s ability to process medications. “Pharmacogenetics” and “pharmacogenomics” are sometimes used interchangeably, but pharmacogenetics more often refers to genetic testing for variants in specific genes, while pharmacogenomics is used in the broader context of whole-genome sequencing or genetics-guided drug development.

Most pharmacogenetic variants are inherited, germline DNA differences that can impact pharmacokinetics (what the body does to the drug) or pharmacodynamics (what the drug does to the body). Pharmacokinetic effects include altering absorption, distribution, metabolism, and elimination, while pharmacodynamic effects may include altering the body’s sensitivity to a drug or altering the drug target itself. Many pharmacogenetic variants are found in genes that code for metabolizing enzymes, while other pharmacogenetic variants can affect proteins that transport medications, play a role in the immune system, or impact the clearance of a specific virus.

Depending on the medication, pharmacogenetic variants may reduce effectiveness, increase the chance of experiencing side effects, or have no effect. Researchers have determined that variants in approximately 20 genes may affect about 80 medications. More specifically, the Clinical Pharmacogenetics Implementation Consortium (CPIC®) has classified approximately 50 gene-drug pairs as having a high level of evidence and being actionable through dosing or medication changes.

It’s worth noting that not all pharmacogenetic variants are inherited; some are acquired DNA changes that are found only in cancer cells. Some oncologists may screen patients for these kinds of variants in order to help target cancer treatments more effectively.

What does it mean to be a “poor,” “intermediate,” “rapid,” or “ultrarapid metabolizer”?

Many pharmacogenetic variants are found in genes that code for metabolizing enzymes, which play a key role in breaking down and eliminating medications from the body. Most of these variants result in enzymes with decreased function, but a few result in enzymes with increased function. Depending on the gene and a person’s specific combination of variants (genotype), they may be classified as a poor, intermediate, normal, rapid, or ultrarapid metabolizer for that specific enzyme.

Poor and intermediate metabolizers process some drugs slower than normal, which may lead to higher drug levels and an increased chance of side effects. But in the case of prodrugs (e.g. clopidogrel), poor and intermediate metabolizers activate prodrugs slower than normal and may experience reduced medication effectiveness.

Rapid and ultrarapid metabolizers, on the other hand, process some drugs faster than normal, which may lead to lower drug levels and an increased chance of non-response with standard dosing. In the case of prodrugs, rapid and ultrarapid metabolizers may activate prodrugs faster than normal and may experience increased medication effectiveness.

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References

Clinical Pharmacogenetics Implementation Consortium (CPIC®). Guidelines. Retrieved February 12, 2020 from cpicpgx.org/guidelines/

Amstutz U et al. (2018). “Clinical Pharmacogenetics Implementation Consortium (CPIC®) guideline for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing: 2017 update.” Clin Pharmacol Ther. 103(2):210-216.

Caudle KE et al. (2017). “Standardizing terms for clinical pharmacogenetic test results: consensus terms from the Clinical Pharmacogenetics Implementation Consortium (CPIC®).” Genet Med. 19(2):215-223.

Caudle KE et al. (2014). “Incorporation of pharmacogenomics into routine clinical practice: the Clinical Pharmacogenetics Implementation Consortium (CPIC®) guideline development process.” Curr Drug Metab. 15(2):209-17.

Chang KL et al. (2015). “Pharmacogenetics: using genetic information to guide drug therapy.” Am Fam Physician 92(7):588-94.

Dunnenberger HM et al. (2015). “Preemptive clinical pharmacogenetics implementation: current programs in five US medical centers.” Annu Rev Pharmacol Toxicol. 55:89-106.

Hicks JK et al. (2017). “Clinical Pharmacogenetics Implementation Consortium (CPIC®) guideline for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update.” Clin Pharmacol Ther. 102(1):37-44.

Hicks JK et al. (2015). “Clinical Pharmacogenetics Implementation Consortium (CPIC®) guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors.” Clin Pharmacol Ther. 98(2):127-34.

Moriyama B et al. (2017). “Clinical Pharmacogenetics Implementation Consortium (CPIC®) guidelines for CYP2C19 and voriconazole therapy.” Clin Pharmacol Ther. 102(1):45-51.

Ramsey LB et al. (2014). “The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1 and simvastatin-induced myopathy: 2014 update.” Clin Pharmacol Ther. 96(4):423-428. (PMID 24918167)

Relling MV et al. (2015). “Pharmacogenomics in the clinic.” Nature 526(7573):343-350.

Relling MV et al. (2011). “CPIC: Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenetics Research Network.” Clin Pharmacol Ther. 89(3):464-7. Website: cpicpgx.org

Scott SA et al. (2013). “Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update.” Clin Pharmacol Ther. 94(3):317-23.

Swen JJ et al. (2011). “Pharmacogenetics: from bench to byte–an update of guidelines.” Clin Pharmacol Ther. 89(5):662-73.

Whirl-Carrillo M et al. (2012). “Pharmacogenomics knowledge for personalized medicine.” Clin Pharmacol Ther. 92(4): 414-417. Website: pharmgkb.org

Change Log

This website may occasionally be updated based on new information.
This Change Log describes updates and revisions.

Date

1 Feb 2020

Change

Pharmacogenetics for Healthcare Professionals website created.

Are you a licensed U.S. healthcare professional?

This pharmacogenetics web portal is intended as an educational resource for healthcare professionals practicing in the United States. Please note it is for informational purposes only and includes information that has not been reviewed by the U.S. Food and Drug Administration.

If you are NOT a licensed healthcare professional, please discuss any questions you have regarding your 23andMe Pharmacogenetics reports with a doctor, pharmacist, or nurse.

Are you a licensed U.S. healthcare professional?*

* Healthcare professionals include doctors, nurses, physician assistants, pharmacists, and genetic counselors.