Introduction
Pharmacogenetics and pharmacogenomics are both integral to the field of personalized medicine, which seeks to tailor medical treatment to individual patients based on their unique genetic makeup. Pharmacogenetics focuses on the study of how an individual's genetic variation affects their response to specific drugs.
By understanding how genetics impact drug metabolism, absorption, and effectiveness, healthcare providers can select the most appropriate treatment for a patient and adjust dosages as needed.
On the other hand, pharmacogenomics takes a broader view by examining an individual's entire genetic makeup to predict their response to drugs across multiple therapeutic areas. This approach allows for more comprehensive and personalized treatment plans.
As the field of pharmacogenomics continues to develop, it has the potential to revolutionize the way we approach healthcare, enabling healthcare providers to identify and treat diseases earlier, more accurately, and with greater precision.
What is Pharmacogenetics?
The study of genetics and how it affects an individual's response to drugs.
Each of us is genetically distinct from the next person. We carry DNA in our cells. Our DNA is grouped into smaller segments that we have defined as genes. Each of our genes represents a set of instructions for the functions of our body. These instructions are also what our body uses to make specific proteins called enzymes. Enzymes activate processes in our body to help our day-to-day life. Drug metabolism enzymes activate or inactivate the medications that we take. In some instances, a specific enzyme may work differently than another person’s. If this occurs, you and that other person may react differently to the same medication. How a gene in our body ultimately affects a medication is called pharmacogenetics.
Pharmacogenetics studies how genetic variations affect an individual’s response to medicines. Identifying these genetic variations allows the prescriber to choose the most appropriate drug treatment and dose for a patient to improve treatment outcomes and reduce adverse drug reactions. Pharmacogenetics is a subset of pharmacogenomics, focusing on the discovery and understanding of how a medicine is affected by a gene.
Examples of pharmacogenetics in healthcare:
Example of drugs affected by our genes:
- Clopidogrel – Clopidogrel, or Plavix, is a common medication prescribed to prevent blood clotting after a heart attack or stroke. Clopidogrel, however, must be changed by our body to its active form to function. Many people do not have the gene that activates clopidogrel leaving them at risk of forming a blood clot even when they think they are being treated. This risk is unknown unless they perform pharmacogenetic testing to determine the status of their gene.
- Omeprazole – Variations in CYP2C19 can affect the concentration of omeprazole and its ability to prevent ulcers, fight gastric reflux, and treat H. pylori infections. Your genetics may determine which proton-pump inhibitor (PPI) would work best in your body.
- Tamoxifen – Patients who are intermediate or poor metabolizers of CYP2D6 may have lower concentrations of the active metabolite leaving them at possible risk of the medication being less effective.
Advantages and disadvantages of pharmacogenetics:
Advantages
- Reduces the chance of avoidable side effects.
- Reduces the need to try multiple different medicines, trial-and-error.
- Reduces cost of healthcare.
- Improves adherence since there are fewer adverse reactions and increased efficacy.
- Improves overall treatment.
- Increases the potential of using the most effective medication.
Disadvantages
- Cost may be prohibitive for some patients.
- Not always necessary, dose adjustments may be sufficient.
- Unwelcome knowledge unrelated to the test.
- May not be the full picture, there may be other health issues or genes that affect the medication in question.
- Knowledge increases daily, the genes tested may not provide a complete picture.
What is Pharmacogenomics?
The study of how an individual's entire genetic makeup affects their response to drugs
Pharmacogenomics testing takes the entire genetic code into consideration when determining if a particular medication may be a poor fit. While there are often only a few genes affecting a medicine directly, there are multiple other genes affecting how the body will react to a medicine. Knowing how your genes are affecting your medications helps to improve treatment outcomes, reduce adverse drug reactions, and improve drug efficacy. Pharmacogenomics helps prescribers choose the best medication first rather than go through a process of trial-and-error.
Examples of pharmacogenomics in healthcare
- Trastuzumab – Variations to the HER2 gene, as well as other genes, can affect a patient’s response. Other genes affecting drug metabolism and immune function may also affect trastuzumab response.
- Abacavir – Patients with HIV should be tested for the HLA-B*5701 gene variant. If they are positive for this gene, abacavir should be avoided. This gene greatly increases the incidence of serious or fatal hypersensitivity reactions. Patients must rely on other anti-viral therapy. In addition, variations of CYP2B6 may also affect metabolism and response leading to lower or higher dose requirements of abacavir.
- Warfarin – Variations in CYP2C9 and VKORC1 may indicate a lower recommended starting dose to obtain the appropriate INR needed. Without knowing a patient’s genetic profile prior to starting, the patient may end up having an excessive bleeding risk. Multiple genes also affect clotting and bleeding risk which then could ultimately affect the most appropriate dosage of warfarin or whether warfarin is a good fit for you.
- You may have issues with producing too little stomach acid. In a case where a medication is required to be acidified to be absorbed, you may not be able to do so as expected.
- With ADHD therapy, any genes that affect your dopamine production may also affect how well you respond to stimulant therapy, the first-line therapy recommended for the treatment of attention deficit hyperactivity disorder. This would be in addition to whether you have a genetic variation that directly affects your medication.
Advantages and disadvantages of pharmacogenomics
Advantages
- Precision medicine – reduced trial-and-error
- Improved safety – reduced incidence of drug-related toxicity, and improved patient safety
- Cost-effectiveness – improves first treatment choices and avoids unnecessary medication
- Faster drug development – identifying drug targets for drug therapy and improve efficiency of clinical trials
- Reduced healthcare utilization – improving treatment outcomes and reducing the risk of adverse drug reactions, reduced need for hospitalizations, and improved patient outcomes
Disadvantages
- Limited availability – pharmacogenomic testing is not always readily available.
- Ethical considerations – genetic privacy, genetic discrimination, and informed consent concerns still exist.
- Limited knowledge – pharmacogenomics is a growing field where not all drug-gene interactions are known.
- Cost – not always covered by insurance.
- Limited clinical guidelines – Guidelines are not available for all medications that may have drug-gene interactions.
What are the differences between Pharmacogenetics and Pharmacogenomics?
Pharmacogenetics and pharmacogenomics both study how a person’s genetic makeup affects their response to medicines. Pharmacogenetics focuses on how a single genetic variation may affect drug metabolism, efficacy, and toxicity. Pharmacogenomics, on the other hand, considers all a person’s genes and how they may influence their drug response.
What are the similarities between Pharmacogenetics and Pharmacogenomics?
- Both use genetic testing to identify specific genetic polymorphisms.
- Both improve drug therapy.
- Both consider environmental factors such as age, gender, diet, and other medications.
- Both are interdisciplinary including genetics, pharmacology, bioinformatics, and clinical practice.
- Both improve patient outcomes.
Conclusion
Pharmacogenetics and pharmacogenomics are related fields of study that focus on how our genes affect our response to medications. Both help optimize medication therapy. Pharmacogenomics encompasses multiple genetic variations and how they affect the absorption, distribution, metabolism, and excretion of our medications; while pharmacokinetics focuses solely on how a genetic variant affects a specific medication. ClarityX offers a simple test to help you and your prescriber better understand how your personal genetics affect your medicines. With the MaxRx test you will be able to predict how over 265 medications will personally affect you. Knowledge is power. Know which medicines are best utilized for you and which ones might best be avoided before you need them.
References
- https://cpicpgx.org/guidelines/cpic-guideline-for-proton-pump-inhibitors-and-cyp2c19/
- https://cpicpgx.org/guidelines/guideline-for-clopidogrel-and-cyp2c19/
- https://medlineplus.gov/genetics/understanding/genomicresearch/pharmacogenomics/
- https://online.epocrates.com/drugs/2043/abacavir
- https://www.drugs.com/monograph/warfarin.html
- https://www.genome.gov/about-genomics/policy-issues/Genetic-Discrimination
- https://www.mayo.edu/research/centers-programs/center-individualized-medicine/patient-care/pharmacogenomics/patients
- https://www.pharmgkb.org/chemical/PA451743/overview
- https://www.pharmgkb.org/labelAnnotation/PA166104819
- Zanger UM, Schwab M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther. 2013;138(1):103-141. doi:10.1016/j.pharmthera.2012.12.007
