Pharmacogenetic testing: CYP2C19

Genes tested in pharmacogenetics

Genes serve as the instructions our bodies use to develop, grow and function throughout our life. In pharmacogenetics (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 variations found in these genes can affect how quickly or slowly an individual processes a medication, influencing the medication’s effectiveness and potential side effects.

What is CYP2C19?

CYP2C19 is a gene that provides the instructions to make the CYP2C19 enzyme, which is involved in the breakdown (metabolism) and activation of medications within the body. This enzyme is mainly found in the liver, which is where it processes certain medications, affecting how well they work and how long they stay in the body.

PGx testing of CYP2C19

Genetic variation—the natural differences in DNA sequences between individuals—can affect how different people process the same medication. Because of specific genetic variation, the CYP2C19 enzyme may work differently from person to person. The results of CYP2C19 PGx testing can predict how quickly or slowly your child is able to metabolize or activate certain medications, which can help their health-care team choose or adjust their medication and dosage.

Medications affected by CYP2C19

Currently, there are many different medication classes and types that are affected by genetic variation in CYP2C19. If your child’s enzyme is predicted to work slower or faster than most individuals, it may affect how these medications work:

• Proton pump inhibitors (PPIs) – medications to help with stomach acid 
  
  • Omeprazole 
    
  • Pantoprazole 
    
  • Lansoprazole 
    
  • Dexlansoprazole 
    
• Antifungal medications – medications to treat fungus growth
  
  • Voriconazole 
    
• Antidepressants – medications that help with feeling sad or anxious 
  
  • Selective serotonin reuptake inhibitors (SRRIs)
    
    • Citalopram 
      
    • Escitalopram 
      
    • Sertraline 
      
  • Tricyclic antidepressants (TCAs)
    
    • Amitriptyline 
      
    • Clomipramine 
      
    • Doxepin 
      
    • Imipramine
      
    • Trimipramine
      
• Antiplatelet agents – medications that prevent blood clotting 
  
  • Clopidogrel 
    
• Abrocitinib, a medication used to treat inflammation in eczema 
  
• Anticonvulsants  – medications to help prevent seizures 
  
  • Clobazam
    
  • Brivaracetam 
    

CYP2C19 metabolizer statuses

The PGx results for CYP2C19 are organized into metabolizer status categories based on the predicted function of the enzyme. Patients may be categorized into one of five groups:

• Poor metabolizer – reduced enzyme activity; your child may break down or activate medication significantly slower than most individuals
  
  • Your child’s health-care team may recommend starting with a lower dose of medication or switching to a different medication to ensure it works safely and effectively for your child.
    
• Intermediate metabolizer – reduced enzyme activity; your child may break down or activate medication slower than most individuals
  
  • Your child’s health-care team may recommend starting with a lower dose or maintaining a reduced dose to help ensure the medication works safely and effectively for your child. 
    
• Normal metabolizer – average enzyme activity; your child is predicted to break down or activate medication at the expected rate
  
  • Most medications should work as expected at standard doses. 
    
• Rapid metabolizer – increased enzyme activity; your child may break down or activate medication faster than most individuals
  
  • Your child’s health-care team may recommend starting with a higher dose of medication to ensure it works safely and effectively for your child.
    
• Ultrarapid metabolizer – increased enzyme activity; your child may breakdown or activate medication significantly faster than most individuals
  
  • Your child’s health-care team may recommend starting with a higher dose of medication or switching to a different medication to ensure it works safely and effectively for your child.

These statuses are not an indicator of your child’s health—they simply predict whether your child might need a different dose of medication or a different medication entirely. In addition to PGx test results, your child’s health-care team will still consider medical history and other factors to ensure the best treatment for your child.

To learn more about drug metabolism, metabolizing enzymes and the metabolizer status scale, see Genetics basics for pharmacogenetics. 

Why is my child’s PGx status important?

CYP2C19 is an enzyme that helps break down certain medications in the body. You can think of it like a drain in a pool that controls how quickly water flows out. The water represents medication.

• If the drain is slow, water builds up. 
  
• If the drain is too fast, water runs out quickly. 
  

Similarly, if your child’s CYP2C19 enzyme is slower or faster than average at breaking down certain medication, the medication might stay longer in the body (causing unwanted effects) or leave the body before it can work properly.

What is a prodrug?

Some medications, called prodrugs, need enzymes to make them work. Think of a glowstick—it does not shine until you crack/bend it. A prodrug is like a glowstick, and the CYP2C19 enzyme helps crack it to “turn it on”. Knowing your child’s CYP2C19 status helps their health-care team choose the right dose and type of medication for your child so it works properly and safely.