What is pharmacogenomics?
Pharmacogenomics (also known as pharmacogenetics) is the study of how our genes affect the way we react and respond to medications. The word “pharmacogenomics” comes from the words pharmacology (the study of the uses and effects of medications) and genomics (the study of genes and their functions). Pharmacogenomics can help a doctor prescribe a medication that leads to fewer side effects or a medication that may work better.
What are genes and DNA?
Deoxyribonucleic acid (DNA) is the material in our bodies that is responsible for what we inherit such as eye color. DNA contains genes and is found in every cell in the body. A gene is the basic “building block” of what we inherit. There are between 20,000 and 25,000 genes in the human body.
Humans have two copies of most genes, one inherited from each parent. Almost all of the genes are the same in every human being, but a small percentage (less than one percent) differ from person to person. This is what makes each individual unique.
Genes help build protein molecules known as enzymes. Enzymes have many functions including the breakdown (metabolism) of medications. Individuals who do not respond to medications as expected may have genetic differences that change the amount of enzymes available to break down a medication or may cause the enzymes not to work.
These genetic differences may have an effect on how someone responds to a medication. If a person breaks down a drug too quickly or too slowly, then a typical dose of a drug can result in side effects, or it may have little to no effect in treating the condition at hand. An individual’s response to a drug also depends on the drug. For example, for drug A, increased breakdown leads to side effects, but for drug B, increased breakdown prevents it from working well.
What is a pharmacogenomic test?
As mentioned above, your body has thousands of genes that you inherited from your parents, and some of these genes are responsible for how your body processes certain medications. A pharmacogenomic test provides additional information to help healthcare providers make treatment decisions for patients with certain medical conditions. Pharmacogenomic testing may be performed for patients receiving medications associated with the treatment of depression, anxiety, and some types of cancer.
How can pharmacogenomics be used?
Pharmacogenomic testing can help doctors decide which medications to use. An individual’s genes may help determine which medications to avoid or how to adjust the dose of a medication allowing a doctor to tailor medications to a patient based on differences in the patient’s genes.
What do the results of a pharmacogenomic test mean?
A pharmacogenomic test can provide information for specific genes that encode cytochrome P450 (CYP450) enzymes, which help the body metabolize drugs. Genetic (inherited) variations (polymorphisms) can make these enzymes have different activities from person to person. That means that the same drug can affect one person differently than it affects another person. With pharmacogenomic testing, the results can examine these variations and predict how fast and how well your body uses different medications and this will help your healthcare provider prescribe medications for you.
A common CYP450 enzyme, for instance, is CYP2D6 which affects how the body processes several medications such as codeine. CYP2D6 has over 100 known variations affecting its activity. Let's use codeine as an example. Some individuals have increased CYP2D6 enzyme activity and break down codeine so quickly that a standard dose can lead to dangerous side effects. Others have decreased CYP2D6 enzyme activity and do not activate codeine to enable it to work, and so they may not get pain relief when taking codeine. Others have normal CYP2D6 enzyme activity and are able to process the medication as expected. Pharmacogenomic testing can help the doctor predict if the patient will not respond well to codeine and if another medication should be used.
Another common CYP450 enzyme is CYP2C19, which is involved in the breakdown of medications such as citalopram and escitalopram. This enzyme also has many known variations that affect its activity. For instance, patients with decreased CYP2C19 activity that are prescribed citalopram for depression or anxiety are unable to break down the medication effectively. This may lead to a buildup of the medication in the body and an increased risk of developing side effects. This may warrant dose modifications or choosing a different medication.
Aside from genetic differences, there may be environmental factors that could affect how a person responds to the medication. Medications themselves have specific characteristics. In the examples above, decreased breakdown of codeine can lead to a lack of effect of the medication while decreased breakdown of citalopram can lead to the development of side effects. Drug interactions may also affect a person’s response to a medication. For example, an individual taking a medication that prevents CYP2D6 from working will not effectively break down codeine even if they have normal CYP2D6 enzyme activity.
Other medications that may be affected by genetic differences include:
- Abacavir (Ziagen®) for HIV infection. A genetic variation in HLA-B can cause a severe skin reaction to the drug.
- Trastuzumab (Herceptin®) for breast cancer. This drug can only be prescribed for women who have a genetic makeup that creates more of a certain protein called HER2.
- Rasburicase (Elitek®) for hyperuremia in cancer patients. Patients who do not carry normal functioning G6PD enzymes are at an increased risk of the body destroying too many red blood cells.
- Azathioprine (Imuran®) for immunosuppression. Changes in the proteins TPMT and NUDT15 can affect how the drug is broken down and could lead to suppression of bone marrow activity.
- Tacrolimus (Prograf®) for organ transplants. Changes in the CYP3A5 enzyme could affect how the drug is broken down. If the drug is broken down too quickly, it can increase the risk of rejecting the transplant organ.
- Allopurinol (Zyloprim®) for gout. A single genetic variation in the HLA-B gene can lead to a painful skin reaction in patients taking allopurinol.
- Clopidogrel (Plavix®) for antiplatelet therapy. A change in the CYP2C19 enzyme in the liver can alter the amount of clopidogrel that is active in your body possibly leading to the drug not working in your body.
What are the potential benefits of pharmacogenomics?
As pharmacogenomics becomes more widely used, it may bring many benefits, including the following:
- Avoiding drugs that may not work or may lead to unwanted side effects.
- Safer prescriptions, because a doctor may be able to predict which drugs and dosages the patient may respond to, with fewer side effects for a patient
- New and more effective drugs for conditions such as pain, nausea and heart disease.
What are the potential limitations of pharmacogenomics?
While an individual’s genetic makeup is important in determining the best treatment for many drugs, it does not explain how all drugs are broken down. There are still medications for which there are no drug-gene tests; the tests only involve some of the many genes in the body. Results of a test represent just one piece of information among many. Other information must be considered when choosing an appropriate medication therapy, such as:
- The person's current medications and how they may affect the breakdown of other medications.
- Any other diseases the person may have.
- The person's lifestyle including diet, exercise, tobacco, and alcohol consumption.
Pharmacogenomics cannot replace a healthcare professional in evaluating a patient and determining the best treatment option.
What happens during a pharmacogenomics test?
During a pharmacogenomic test, a healthcare provider collects a sample of your DNA, which is the material in your cells that carries genetic information. The DNA is sent to a laboratory where a technician studies the changes in your DNA that may change specific enzymes that help your body process medications.
Collecting a DNA sample takes only a few minutes. At your visit, one of these methods will be used:
- Blood test: Inserting a needle into a vein in your arm to draw a small sample of blood.
- Cheek swab: Rubbing a cotton swab inside your cheek to collect cells.
- Saliva collection: Using a collection tube to gather your saliva.
How do I prepare for a pharmacogenomic test?
If a cheek swab is needed to collect DNA, please do not smoke, chew gum, eat or drink anything for at least 30 minutes prior to sample collection. If a blood test is necessary to collect DNA, most individuals do not need to do anything to prepare. Your healthcare provider will provide any further specific instructions for you if necessary.
Is pharmacogenomic testing covered by insurance?
Insurance companies are different from each other and have different benefits and coverage for pharmacogenomics testing. Some may cover the test when it is seen as medically necessary. Your healthcare provider will work with you to help determine if your insurance will cover this test, however there may be out-of-pocket costs associated with testing.
How can genetic information be protected?
To help prevent discrimination based on genetic results, the Genetic Information Nondiscrimination Act (GINA) was passed in 2008. The law prevents discrimination and harassment based on someone’s genetic information and potential for disease. GINA prohibits an employer from using genetic information to make an employment decision as well as retaliation against someone who files a charge of genetic discrimination. The protections GINA offers for insurance apply only to health insurance. GINA does not apply to life, long-term care, or disability insurance. Additionally, GINA does not apply to individuals with military insurance.
Where can I learn more about pharmacogenomic testing?
You can learn more about pharmacogenomic testing from The Center for Personalized Genetic Healthcare (CPGH) at Cleveland Clinic.