A Complete Guide to Pharmacogenetics

For individuals and caregivers.
In 510 BC, a Greek philosopher known as Pythagoras of Samos (the same man who created the Pythagorean theorem) noticed a connection between eating fava beans and a blood disorder, haemolytic anaemia, in some individuals. According to some stories, Pythagoras feared fava beans as a result. Though over 2,500 years ago, Pythagoras’ discovery is considered the first landmark event in the history of pharmacogenetics. It wouldn’t be until 1956 that the dangers of ingesting fava beans were attributed to a deficiency of an enzyme called glucose-6-phosphate dehydrogenase (G6PD).1 This enzyme is involved in processing carbohydrates and protects red blood cells from certain harmful molecules. What does this have to do with pharmacogenetics? The instructions for creating this enzyme come from the G6PD gene.2 In other words, genetics can impact the way your body metabolizes and interacts with what you ingest. This is true whether you’re discussing food or, in the case of pharmacogenetics, medications. In this complete guide to pharmacogenetics, you will learn everything from how it works to why it matters.

What is pharmacogenetics?

Pharmacogenetics (PGx) brings together two fields of science, pharmacology and genetics, to help healthcare providers individualize care for their patients.

Pharmacogenetics is often used interchangeably with pharmacogenomics, but these terms actually have slight differences in meaning. What’s the difference between pharmacogenetics and pharmacogenomics?

Simply put, pharmacogenomics is the study of how all genes (the genome) can affect responses to drugs.

When referring to how an individual gene variant can impact a response to a single drug, scientists use the term pharmacogenetics.

What is the purpose of pharmacogenetics?

The purpose of pharmacogenetics is to help provide genetic guidance for three important aspects of prescribing: drug efficacy, dosage, and prevention of side effects.

  • Efficacy: Which medications may be more effective.
  • Side Effects: Which medications may have unpleasant or dangerous effects.
  • Dosage: What dosing may be appropriate based on how your body metabolizes medication.

How does genetics affect drug response?

One of the main functions of genes is to provide your cells with instructions for making proteins.

Proteins are molecules responsible for many bodily functions, for example, the structure of cells, and the regulation of tissues and organs.

One important example is how certain proteins are responsible for the metabolism (breaking down) of many commonly-used drugs.

Because there are different versions of genes, the instructions for proteins vary, and the way your body interacts with a drug may also vary as a result. These genetic variations are important for healthcare providers to consider when making prescribing decisions.

There are two primary mechanisms used to understand the way genetics can impact an individual’s response to medications: pharmacokinetic effects and pharmacodynamic effects.

Pharmacokinetics (PK)

Pharmacokinetics has to do with what your body does to a drug and the movement of a drug within your body.3 This includes absorption, distribution, metabolism, and excretion. Metabolism and absorption are extremely important when understanding how much of a drug to prescribe and potentially dangerous side effects for an individual. Here’s how it works: Your genes provide the blueprints for the proteins that control metabolism and absorption in your body. Variations in these blueprints can impact the speed at which these processes happen. If your body metabolizes a drug too quickly, you might not receive any benefits. If your body metabolizes a drug too slowly, you might experience side effects or toxicity. The speed at which your body breaks down a drug can help inform the amount, or dose, a clinician prescribes for you. In some cases, it can help a doctor avoid giving you a potentially harmful drug altogether. Your genes also influence how quickly or slowly you absorb a drug. This can have a similar impact on efficacy and safety.

Pharmacodynamics (PD)

Pharmacodynamics can be described as what a drug does to the body, or the study of biochemical, physiologic, and molecular effects of a drug on the body.4

Here’s how it works:

When a drug enters your body, it usually starts interacting with cell receptors, which creates a signal that leads to a biological response.

This part can get a little complicated, but here’s the short version:

Variations in genes can lead to variations in cell receptors or other drug targets, and that can lead to variations in biological drug response.

Pharmacodynamics can help predict the effect a particular drug may have on an individual and may help inform drug choice.

How does pharmacogenetic testing work?

  1. Pharmacogenetic testing is typically administered with a simple cheek swab to collect a buccal sample, much like commercial DNA tests.
  2. The sample is evaluated by a certified laboratory technician, who looks for specific gene variants associated with altered drug metabolism or differential therapeutic effects (like adverse side effects).
  3. The laboratory technician reports the results electronically to the licensed healthcare provider to be used in prescribing guidance.

Because pharmacogenetic testing provides guidance for prescription medications, PGx testing (in the United States) requires a prescription from a licensed healthcare provider.

How accurate is pharmacogenetic testing?

Different pharmacogenetic tests analyze different genes, and laboratory accuracy can vary. When choosing a pharmacogenetic test, look for laboratory accuracy. Also, check to see if a company provides transparent information about evidence from trusted pharmacogenetic sources.

Trusted Pharmacogenetic Sources

Pharmacogenetics, much like any field of science, is constantly evolving as new research is released and new discoveries are made. However, that does not mean that all evidence is equal. In a clinical setting, scientific evidence is ranked in a hierarchy referred to as levels of evidence.5 Strength of evidence is an important consideration, and there are several key sources for pharmacogenetic guidance that help standardize this information.

FDA Labels and Pharmacogenetic Associations

The FDA has genetic-based guidance on over 270 medications, and their table of pharmacogenetic associations is publicly available on the FDA website. In fact, when available, you can find this guidance in the prescribing information that accompanies the drug. Each association has been carefully evaluated to determine if it is backed by sufficient scientific evidence.6

Clinical Pharmacogenomics Implementation Consortium (CPIC)

CPIC plays a key role in standardizing pharmacogenetics and produces peer reviewed PGx guidelines. You can view their full Genes-Drugs table online.

PharmGKB’s Extensive Database

PharmGKB is a trusted database for pharmacogenetics that includes over 700 drug label annotations and more than 150 curated pathways.

Royal Dutch Pharmacists Association (KNMP)

KNMP is the Dutch pharmacist trade organization that founded DPWG (Dutch PGx Working Group). DPWG is a consortium of researchers in Europe who work together to translate PGx research into clinical guidelines.

Should genetics be considered before giving a person a drug?

Personalized medicine is becoming increasingly common and more routine in today’s world. For decades, certain pieces of the puzzle have been considered when making prescribing decisions, like family history, environmental factors (such as smoking), lifestyle, and other medications an individual may be taking.

Genetics represents a missing piece of the puzzle that is now accessible through pharmacogenetic testing. PGx tests are designed to help reduce trial and error prescribing and assist healthcare providers in making safer medication choices.

At Genomind, we are committed to providing the most advanced and comprehensive pharmacogenetic testing for mental health. We believe genetics is a crucial factor to consider before prescribing a medication.

If you would like to learn more about our test and services, visit our Genomind Pharmacogenetic Testing page.

Sources

  1. Carson, P. E., Flanagan, C. L., Ickes, C. E., & Alving, A. S. (1956). Enzymatic Deficiency in Primaquine-Sensitive Erythrocytes. Science, 124(3220), 484–485. https://doi.org/10.1126/science.124.3220.484-a
  2. MedlinePlus. (2020, September 9). Glucose-6-phosphate dehydrogenase deficiency: MedlinePlus Genetics. https://medlineplus.gov/genetics/condition/glucose-6-phosphate-dehydrogenase-deficiency/
  3. Merck Manuals. (2020, October). Overview of Pharmacokinetics. Merck Manuals Professional Edition. https://www.merckmanuals.com/professional/clinical-pharmacology/pharmacokinetics/overview-of-pharmacokinetics
  4. Merck Manuals. (2019, June). Overview of Pharmacodynamics. Merck Manuals Professional Edition. https://www.merckmanuals.com/professional/clinical-pharmacology/pharmacodynamics/overview-of-pharmacodynamics
  5. Burns, P. B., Rohrich, R. J., & Chung, K. C. (2011). The Levels of Evidence and Their Role in Evidence-Based Medicine. Plastic and Reconstructive Surgery, 128(1), 305–310. https://doi.org/10.1097/prs.0b013e318219c171
  6. Center for Devices and Radiological Health. (2020, March 18). Table of Pharmacogenetic Associations. U.S. Food and Drug Administration. https://www.fda.gov/medical-devices/precision-medicine/table-pharmacogenetic-associations#about