by Raeanne Geffert
Your genes (which are found in your DNA) hold information about yourself. Genes are passed down from your parents and are the instructions on how your body builds proteins. The genes you have determine things like your hair type, height, and eye color, and can affect the number and type of proteins your body makes. Some of these proteins are enzymes, which are proteins that perform chemical reactions in your body. Enzymes are the main way that medicines are removed from your body, usually through your liver. Your genes tell your body how many and what kind of enzymes to make in your liver. Drugs usually fit well into one of these enzymes and not in other kinds of enzymes- this process is similar to a lock and a key (see figure below). If you have a higher number of one type of enzyme, then this means the drug that fits with this enzyme might leave your body really quickly. If you don’t have enough of a certain enzyme, a certain medicine may not work for you. This is all based on your DNA, making it a critical part of how medicines work for you.
Your genetics (DNA) can affect how much and what type of enzymes (proteins) are in your liver. This can influence which type of medication your doctor prescribes for you. (Created by author with Biorender.com).
Pharmacogenomics (also called pharmacogenetics, abbreviated as PGx) is the field of study based on researching how a person’s genes affect how they respond to certain medicines. This field is relatively new as we began studying human DNA in the 1950s. Pharmacogenetic scientists are interested in understanding different types (or variants) of a certain enzyme and how each type affects the effectiveness of medications. These variants can have different effects. For example, some people only have one copy of a gene, and they have normal activity in the enzyme. However, some people have two copies of the same gene and this results in more of that enzyme. The number of enzymes present can affect how much and how quickly a drug is removed from your body. This could be the difference between a medicine helping you or actually hurting you!
Some medicines can have toxic side effects when you take a certain dose, so knowing what genes you have can be really important when you need to take medicine. There are pharmacogenetic tests available for genes that we know have variants that can really affect the effectiveness of some drugs. These tests can use blood samples, cheek swabs, or even saliva samples, and some tests can be mailed to you to complete at home. Companies will provide this genetic information to you, but you need a doctor or a pharmacist to interpret the results. These tests work because we know the specific gene that we are interested in, and we can perform a test to determine whether the gene we expect is in your DNA or if there is a variant there. However, it is important to remember that pharmacogenetic testing is not genetic testing. Pharmacogenetic testing helps physicians understand how you will eliminate a drug from your body so that they can make decisions about the amount of the drug you should take based on that information.
Pharmacogenetic testing is required for some medicines before you can take them. One example of this is the blood thinner drug called clopidogrel. This drug is metabolized, or removed from the body, by an enzyme known as CYP2C19 in the liver. There are different variants of CYP2C19, and some variants can result in lower amounts of the enzyme, also known as a “poor metabolizer”. If a person is a poor metabolizer, it is recommended that they do not take clopidogrel because the medication will not work as well for them as it does for those with more of the enzyme present. There is a consortium dedicated to helping doctors and pharmacists by providing guidelines for drugs that have “actionable PGx”, which is pharmacogenetic information that is relevant to patients. This consortium recommends pharmacogenetic testing for clopidogrel before patients take the medication to ensure that they will benefit from taking the drug.
Scientists are working on conducting studies to determine other drugs that might need pharmacogenetic testing. As new drugs continue to be made by companies, these drugs will also need to be tested and their pharmacogenetic effects will need to be studied. Though, there are not many drugs that require pharmacogenetic testing right now. Pharmacogenetics is a key part of making healthcare more personalized and tailored to each patient. This interesting field is evolving everyday, and might become a standard part of your visit to the doctor someday soon.
