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The Genes Examined in Prairie’s Pharmacogenomic Test

There are a variety of reasons to undergo genetic testing: screening for hereditary conditions, discovering ancestry, and — in Prairie’s case — providing information about how your body processes mental health medications.

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There are a variety of reasons to undergo genetic testing: screening for hereditary conditions, discovering ancestry, and — in Prairie’s case — providing information about how your body processes mental health medications. Specifically, when you sign up with a Prairie psychiatrist, you have the option of pharmacogenomic (or pharmacogenetic) testing. This test describes how your body responds to certain medication. Our psychiatrists use your pharmacogenomic test results to build a treatment plan more likely to work, by ruling out genetically incongruent medications and setting an appropriate starting dosage.

Our genetic tests primarily focus on five specific genes:

  1. CYP2D6
  2. CYP2C19
  3. CYP2C9
  4. CYP1A2
  5. CYP3A4

Why these genes?

Each of the genes tells the body how to make a type of enzyme (a type of protein). These specific enzymes metabolize medication in the body. This involves breaking it down into smaller components that the body can use.

Let’s look at each specific gene and how it relates to medication.

CYP2D6 is a pharmacogene that allows for the creation of enzymes in the liver. The enzymes created by CYP2D6 are responsible for up to 20% of the body’s ability to break down various different drugs, including many common antidepressants.

CYP2C19 is another gene that gives instructions for producing liver enzymes. This gene produces enzymes that are responsible for the breakdown of at least 10% of the most commonly prescribed drugs.

CYP2C9 codes for an enzyme that is most known for breaking down steroid hormones and fatty acids. However, it can also contribute to the breakdown of the drug fluoxetine (i.e. Prozac), which is often used to treat depression.

CYP1A2 creates an enzyme that metabolizes the antidepressant fluvoxamine (i.e. Luvox).

CYP3A4 is a very important gene that produces an enzyme that contributes to our metabolism of up to 50% of all drugs on the market.

The body would not be able to process various forms of medication without these genes and the enzymes they produce. Thus, understanding how these genes function in the body helps us understand how our body processes various drugs.

Why conduct pharmacogenomic testing at all?

Before the 1993 NIH Revitalization Act, drug companies were not required to include women and people of color in their trials. This means that the prescriptions guidelines that were created then and exist until today cater to white men.

As a result of genetic differences, women are likely to metabolize drugs more slowly than men. Thus, dosage guidelines that work for men often are less effective for women.

There are also genetic variations between different ethnic groups. For example, researchers have discovered that a certain form of CYP2D6 is present in 71% of people with European ancestry, but only 50% of people with Asian ancestry. This means that a drug with a certain relationship to CYP2D6 might work better for a white American than their Chinese-American counterpart.

The pharmacogenomic test allows Prairie to pinpoint factors that might affect a person’s biological response to medication. Prairie then crafts a prescription plan with more personalized dosages and reduced side effects.

What do doctors look for in a pharmacogenomic test?

Genetic tests look for variations in genes that can cause differences in how those genes function. Each gene that Prairie looks at functions in one of three basic ways, called phenotypes. The three basic phenotypes are:

  1. Rapid metabolizer
  2. Slow metabolizer
  3. Extensive metabolizer

If a gene displays a rapid metabolizer phenotype, the enzyme created by that gene breaks down chemicals very quickly.

Genes with a slow metabolizer phenotype have an equally applicable name; the enzymes created by these genes would break down chemicals much more slowly.

On the other hand, an extensive metabolizer breaks down chemicals at a normal rate.

Prairie uses phenotype information to guide our prescription practices.

How are my pharmacogenomic test results used?

When your doctor gets the results of your pharmacogenomic test, like in the example above, they are able to get a better picture of whether you have the rapid, slow, or extensive metabolizer phenotype for each gene. Different metabolic rates means that substances will stay in your body for shorter or longer periods of time . This affects your bloodstream concentrations and therefore impacts both efficacy and side effects.

For example, a variation of CYP2D6 leads to the slow metabolism of atomoxetine (i.e. Strattera), a drug commonly used to treat depression. When atomoxetine isn’t broken down quick enough, it can build up in the bloodstream. This can lead to increased incidence of side effects such as elevated blood pressure and heart rate, dry mouth, and insomnia. A psychiatrist treating a patient with this genetic variation might reduce the standard dosage to help prevent such side effects.

In another instance, having a certain variant of the CYP2C19 gene means that your body might process Citalopram (i.e. Celexa), a type of antidepressant, more quickly. This might lead to the medication being less effective at the standard dosage. The Clinical Pharmacogenetics Implementation Consortium (CPIC) urges psychiatrists to consider prescribing a different antidepressant for those who might have this problem.

Conclusion

Every company that conducts genetic testing has a mission that guides its work. Prairie’s is to leverage research and technology to empower everyone to achieve better mental health.

There is a degree of subjectivity in every form of mental healthcare. Conducting simple and transparent genetic testing helps psychiatrists make more informed decisions. This will ultimately help clients reach their optimal treatment plan more quickly.

Want to learn more? Check out this blog post by one of our founders describing the benefits of incorporating pharmacogenomic testing into mental health treatment. Confused about what your test results mean? Check out this blog post explaining how to make sense of your results.

To learn more about pharmacogenomic testing and whether you’re likely to benefit from getting tested, take our free pharmacogenomics quiz.

Take our quiz

Thu Jan 21 2021

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