What is pharmacogenetics?
Pharmacogenetics (PGx) combines the words "pharmacology" (the study of how medications affect the body) and "genetics" (the study of differences between individuals and how these traits are inherited within families). PGx is a type of precision medicine and is the study of how genetic variation can influence an individual’s response to medications.
Genes used in pharmacogenetics
Genes serve as the instructions our bodies use to develop, grow and function throughout our life. They are made up of specific “building blocks” that determine their function in the body. Genetic testing looks at the particular arrangements or “spelling differences” of these building blocks in an individual’s set of genes.
In PGx, genes are tested for their association with predicted medication response. Most genes analyzed in PGx testing provide instructions for enzymes. Enzymes are proteins in the body that help process medications by either activating them or breaking them down (metabolizing them). Genetic variation found in these genes can affect how quickly or slowly an individual processes a medication, influencing the medication’s effectiveness and potential side effects.
Most of the PGx genes currently tested are involved in drug metabolism, while others are involved in different processes, such as drug transportation (allowing medications to cross membranes in the body). Some PGx genes are not directly involved with the processing of medications but impact how individuals respond to medication through hypersensitivity-based reactions.
What is drug metabolism?
Drug metabolism refers to the breakdown of a drug in the body. This process can trigger the activation of a drug so it can do its intended function, or it can trigger the breakdown of a drug so the drug can be removed from the body. Some medications called prodrugs are inactive until the enzymes in the body process them to make them work.
No matter the type of drug processing reaction, all drug metabolism is facilitated by enzymes in the body. Through PGx testing, people are classified on the metabolizer scale based on their predicted metabolizer status. The scale ranges from poor metabolizers to ultrarapid metabolizers, with normal metabolizers usually representing the average population. A poor metabolizer is predicted to have slow enzyme activity, whereas an ultrarapid metabolizer is predicted to have faster enzyme activity. If enzymes work too slowly (poor metabolizer), a medication might stay in the body longer, which can cause unwanted effects. If enzymes work too fast (ultrarapid metabolizer), a medication may be cleared from the body too quickly and not work as intended.
What are drug metabolizing enzymes?
Enzymes are proteins in our cells that support various biological processes needed for a healthy body. Drug metabolizing enzymes are specifically involved in the metabolism of medications.
Enzymes are produced from genetic instructions encoded in our DNA. Genetic variation can result in enzymes being built slightly differently, which may alter enzyme functions. In PGx, enzymes act like machines, helping to convert drugs into their active form and ensuring the breakdown of a medication. Genetically altered enzymes may break down a medication at a different rate than expected, potentially affecting the drug’s effectiveness or safety.
What are drug transporters?
Transporters are proteins in our cells that assist in moving different chemicals to where they are needed in the body. Drug transporters specifically allow medications to cross cell membranes, so those medications get to where they are needed in the body.
Transporters are produced based on genetic instructions encoded in our DNA. Genetic variation can also result in transporters being built slightly differently, which may alter their functions and drug response. Genetically altered transporters may allow a medication to cross membranes at a different rate than expected, potentially affecting the drug’s effectiveness or safety.
How do genes relate to medication use?
PGx testing helps in understanding a person’s genetic variation, allowing for individualized and effective medication management. Differences in the “spelling” of these PGx genes can help explain how a person may experience potential side effects or (in)effectiveness from a medication.
Some of the genes that can currently be tested through PGx testing include the following:
Variation in these genes can impact responses to medications that are used in the treatment of pain, mental health, heart health, digestive health, infectious disease, cancer, autoimmune disorders and nerve disorders.
Since genetic information remains largely unchanged throughout life, PGx insights may predict responses not only to current medications but also to those that may be prescribed in the future.