How accurate is pharmacogenetic testing?Veronika Litinski, MSc Medicinal Chemistry, MBA
Pharmacogenetics uses a patient’s genetic profile to accurately predict a drug’s efficacy, guide dosage and improve the safety of treatments. Depending on your genetic makeup, some medications may work faster or slower, or produce more or fewer side effects. The scientific field of pharmacogenetics, the link between your unique genetic variations and drug response, began over 70 years ago. Since then, there has been a tremendous expansion of scientific evidence in the field, and there are now well-established pharmacogenetic (PGx) prescribing guidelines for doctors and pharmacists to follow. In addition, accurate and affordable pharmacogenetic testing is becoming more widely available.
What genes should be tested?
In general, a genetic test looks for variants in a person’s DNA. The DNA variants included in a particular genetic test vary depending on the genetic testing provider and the goals of the test. A genetic test will examine a chosen collection of variations in your DNA (from more than 20,000 genes in the human body) that are known to be of interest. These variants are why some people have curly hair or hate cilantro or metabolize certain drugs faster. Whether or not it is useful to find out that you are distantly related to the King of Spain is a matter of personal opinion. Medically speaking, genetic tests can screen for cancer, identify developmental abnormalities in fetuses, and in the case of pharmacogenetics, help us understand how we process prescription medications.
Some tests use a single variation in a single gene to predict something like how well you tolerate caffeine or what type of exercise you should be doing. This can be problematic. Many thousands of interconnected chemical reactions occur in our cells to extract energy from sugar, build muscle, or get headache relief from a Tylenol. This involves a lot of genes working together. And the more complex the process, the more genes are involved. A genetic test must look at many genes or one gene in great detail to gain useful health information. The exception is rare diseases, but that’s a different story.
The technology used for genetic testing can also differ depending on the goals of the test and the level of detail required. At 23andMe, a genotyping DNA chip scans 600,000 or so variants to provide a “big-picture” of the individual. However, such ancestry tests often overlook key genetic variants that impact disease risk or medication response. Other types of genotyping tests can be more focused. Some tests focus on variants found in a specific area of the DNA or on a category of genes (such as drug metabolism genes). Clinical pharmacogenetic testing services, such as Pillcheck focus directly on the genes that impact drug response.
How does genetic testing for medications work?
Pharmacogenetic tests like Pillcheck use a simple cheek swab to collect genetic material from your saliva. Once the certified clinical laboratory has processed the DNA in the sample, it becomes digitized. Then a record of the individual’s genetic markers is scanned against a list of known genetic variants associated with a varied response to medications. Mutations at specific locations in a gene account for diversity in humans and the differences in how our bodies process medications.
To predict something complex, let’s look at the process where your liver converts the drug codeine, an ingredient found in many prescription medications like Tylenol 3, into morphine, which is the chemical that provides the pain relief. Genetic variations dictate how rapidly the liver converts codeine into morphine. If your liver enzyme is really, really fast at this, it can turn standard doses of codeine into a toxic or even fatal amount of morphine in the body.
Can heritage affect drug disposition?
To determine how fast the liver converts codeine, we need to look at a group of genetic variations that work together for this process. The more genetic markers we include, the more accurate and higher definition the test is. PGx tests like Pillcheck include markers that are critical for doctors and pharmacists to guide prescribing decisions. Other more general genetic tests, which sometimes include limited pharmacogenetic results, do not include these markers.
In addition to the relevant genetic markers needed to make prescribing decisions, clinical-grade tests must also look for extra copies of genes to ensure that significantly increased metabolism of medications is detected. To learn more about this, see our blog How to get a pharmacogenetic test in Canada.
In situations where we know a particular genetic variation is much more common in some racial or ethnic groups, a test like Pillcheck with high sensitivity means a greater proportion of people can receive accurate results for more medications, regardless of ethnicity.
For example, the risk of death due to the excessive conversion of codeine into morphine is thought to vary by ethnicity. In fact, it is directly associated with the presence of multiple functional copies of the gene encoding a specific liver enzyme, CYP2D6. Think of this as a high-definition television compared to older technology. Why watch standard-definition (SDTV) (576i) when you can have a crystal-clear picture? In the case of pharmacogenetics, high-definition testing can have definite benefits for a person’s treatment. Why compromise quality when it comes to your health?
Do all drugs have pharmacogenetic guidelines?
Genetic testing isn’t a magic solution to a person’s health challenges, but it can provide your doctor with critical information about how your body will metabolize certain medications. The majority of prescription medications, over 70%, are metabolized in the liver: i.e. they rely on the activity of liver enzymes, which is determined by your genetics. The Pillcheck service provides transparent reporting for medications used to treat a wide range of conditions, according to clinically established guidelines provided by Health Canada, the FDA, and CPIC, the gold standard in pharmacogenetic reporting.
How do I get the most benefit from my pharmacogenetic results?
Pharmacogenetics is a companion tool for prescribers, and you should make sure to share your results with your physician. Expert clinicians who have extensive PGx experience note that test results frequently identify the reasons for past medication intolerability and failure. Understanding why previously prescribed drugs resulted in poor experience (and stopping treatment) can help reassure patients that their experience was legitimate and gives them the confidence to try a new medication that is more compatible with their genetics.
How to talk to your doctor about finding the right medication?
Medical expertise is needed to assess PGx insights and make changes to your therapy. That’s why the Pillcheck service includes a medication review by a clinical pharmacist who will assess your medications in the context of your genetic analysis.
- Medications you’re currently taking (including over-the-counter and supplements)
- Medications taken in the past and any side effects
- Symptoms currently experienced
- Alternative medications or dosage to consider in making treatment more tolerable and effective
- A clinical-grade pharmacogenetic (PGx) test can accurately predict the rate of drug metabolism and clearance based on an individual’s genetic makeup. A doctor considers many factors to find the safest and most effective medication for a person, and Pillcheck can help guide these decisions.
- Predicting something complex, such as how individuals of different ethnicities respond to various medications, requires a sophisticated genetic analysis of many genes working together. Tests like Pillcheck include this analysis so that more people, regardless of ethnicity, can get accurate answers to how they’ll respond to more medications.
- The Pillcheck service provides transparent reporting for a wide range of conditions, all according to clinically established guidelines provided by Health Canada, the FDA, and CPIC, the gold standard in pharmacogenetic reporting.
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User considerations in assessing pharmacogenomic tests and their clinical support tools https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133969/
Recommendations for Clinical CYP2C19 Genotyping Allele Selection: A Report of the Association for Molecular Pathology https://jmd.amjpathol.org/article/S1525-1578(17)30519-6/pdf
Pharmacogenetics in Psychiatry: A Companion, Rather Than Competitor, to Protocol-Based Care https://pubmed.ncbi.nlm.nih.gov/30167635/
Pharmacogenetics Guidelines: Overview and Comparison of the DPWG, CPIC, CPNDS, and RNPGx Guidelines https://www.frontiersin.org/articles/10.3389/fphar.2020.595219/full