Pharmacogenetic (PGx) testing can be highly accurate in identifying genetic variants that may affect an individual's response to certain medications.
Accuracy of the testing, however, can vary depending on factors such as the quality of genetic samples, specific variants tested for, and the interpretation of the results by a trained healthcare professional.
Pharmacogenetic Testing is a Type of Precision Medicine
“Pharmacogenetic testing is a type of precision medicine,” says the National Library of Medicine. “Precision medicine uses information about your genes, environment, and lifestyle to find out which approaches to disease treatment and prevention will work best for you.”
Pharmacogenetics (also called pharmacogenomics) is the study of how your genes affect the way your body responds to certain medicines.
“Some genes also affect how your body uses and breaks down medicines. Differences in these genes can be the reason why some people may benefit from a certain medicine while others may not benefit at all. Genes can also be the reason why some people have serious side effects from a medicine and others have none,” says the National Library of Medicine. “Pharmacogenetic testing provides information about your genes to help your health care provider choose the medicine and dosage that are the "best fit" for you.”
Pharmacogenetic testing may be used to:
- Find out whether a certain medicine could be effective for you.
- Find out how much of the medicine you need.
- Predict whether you will have a serious side effect from a medicine.
Pharmacogenetic testing was associated with nearly a two-fold (89 percent) increase in remission rates compared to treatment as usual in a Centre for Addiction and Mental Health-led clinical study published in the journal Translational Psychiatry in 2022.
Another study, published in BMC Psychiatry in 2017, showed the results from a 12-week, double-blind, parallel, multi-center randomized controlled trial in 316 adult patients with major depressive disorder (MDD) and found that “PGx-guided treatment resulted in significant improvement of MDD patient’s response at 12 weeks, dependent on the number of previously failed medication trials, but not on sustained response during the study period. Burden of side effects was also significantly reduced.”
Of course, the accuracy of PGx testing is dependent on several factors.
Quality of Genetic Samples Can Affect PGx Testing Accuracy
First, the accuracy of pharmacogenetic testing depends on the quality of the genetic sample analyzed.
Factors such as the type of sample collected (e.g., blood, saliva), how the sample was stored, and the DNA extraction method used can all affect the accuracy of the test results.
Here are some examples:
- Insufficient amount of DNA: If the sample contains an insufficient amount of DNA, the genetic analysis may not be accurate or may even fail altogether. This can happen if the sample was not collected properly, or if the DNA was degraded during storage or handling. For example, a small amount of saliva sample collected with a swab may not yield enough DNA for an accurate analysis.
- Contamination: Contamination of the sample with other genetic material can also affect the accuracy of the genetic analysis. This can occur if the sample was not collected in a sterile environment or if the sample was contaminated during processing. For example, if blood is collected with a contaminated needle or is not handled properly, the sample may be contaminated with other genetic material, leading to inaccurate results.
- Genetic variants not detected: The quality of the genetic sample can also affect the detection of specific genetic variants. If the DNA is degraded or fragmented, certain variants may not be detectable or may be detected with lower accuracy. For example, if a blood sample is not stored properly, the DNA may degrade over time, making it more difficult to detect specific genetic variants accurately.
The quality of the genetic sample being analyzed is crucial for the accuracy of pharmacogenetic testing.
It is essential to collect and store samples carefully and to ensure that the genetic analysis is performed using reliable methods.
Specific Genetic Variants Tested for Can Affect PGx Accuracy
The accuracy of pharmacogenetic testing also depends on the specific genetic variants tested for.
Some genetic variants have been well-studied and have a strong association with drug response, while others may have weaker associations or are not well understood. The following can affect the accuracy of PGx testing:
- Lack of understanding: Some genetic variants may not have been well-studied or understood, which means that their effects on drug response are unclear. In these cases, the accuracy of pharmacogenetic testing may be limited by our current knowledge of the variant. For example, the impact of the ABCG2 genetic variant on the response to certain chemotherapy drugs is not yet fully understood.
- Population differences: Some genetic variants may be more prevalent in certain populations, which means that their impact on drug response may vary depending on a person's ethnicity. If the genetic test is not designed to detect variants that are specific to a certain population, it may not be accurate for that population. For example, the CYP2C9 genetic variant that affects warfarin metabolism is more prevalent in some Asian populations compared to other populations.
- Multiple genes involved: Drug response is often influenced by multiple genetic variants, which means that testing for only one variant may not provide a complete picture of a person's drug response. In some cases, testing for a single genetic variant may not be accurate for predicting drug response, and testing for multiple variants may be required. For example, testing for multiple genetic variants can help predict a person's response to clopidogrel, a blood thinner.
It is important to consider the limitations of the genetic test when interpreting the results.
Understanding the current state of knowledge of genetic variants and their effects on drug response can help healthcare providers make informed decisions about medication management.
Interpretation of Pharmacogenetic Testing Results Crucial
Finally, the accuracy of pharmacogenetic testing also depends on the interpretation of the results.
The test results must be interpreted by a trained healthcare provider who can consider a patient's medical history, current medications, and other factors that may affect their response to a medication.
Some important factors to consider when interpreting PGx test results:
- Specific Drugs: The healthcare provider should consider which medications the patient is taking or is likely to take, and which genetic variants are relevant for those drugs. For example, if a patient is taking warfarin, the healthcare provider should consider the impact of the patient's CYP2C9 and VKORC1 genetic variants on warfarin metabolism and dose requirements.
- Clinical Relevance: The healthcare provider should consider the clinical relevance of the genetic variants tested for. Some genetic variants may have a well-established association with drug response, while others may be less well-understood or have limited clinical relevance. The provider should consider the strength of the association and the level of evidence supporting the variant's impact on drug response.
- Impact on Dosing: The healthcare provider should consider whether the patient's genetic variants may impact dosing requirements for medications. For example, a patient with a CYP2D6 ultrarapid metabolizer status may require higher doses of codeine or tramadol to achieve adequate pain relief.
- Impact on Efficacy: The healthcare provider should consider whether the patient's genetic variants may impact the efficacy of medications. For example, a patient with a reduced-function CYP2C19 genetic variant may have a reduced response to clopidogrel, a blood thinner.
- Impact on Toxicity: The healthcare provider should consider whether the patient's genetic variants may increase the risk of medication toxicity. For example, a patient with a reduced-function UGT1A1 genetic variant may be at increased risk for toxicity from irinotecan, a chemotherapy drug.
- Ethnicity: The healthcare provider should consider the patient's ethnicity and whether the genetic variants tested for are relevant for that population. For example, the CYP2C19*2 genetic variant is more common in Asian populations compared to other populations, and testing for this variant may be particularly relevant for Asian patients taking certain medications.
- Other Clinical Factors: The healthcare provider should consider other clinical factors that may impact medication management decisions, such as the patient's medical history, current medications, and other factors that may affect their response to a medication.
While pharmacogenetic testing can be highly accurate, it is important to consider these factors when interpreting the results and making decisions about medication management.