~ The CYP2C9 gene encodes an enzyme that breaks down certain medications as well as key substances in the body, such as serotonin and arachidonic acid.
~ Variants in CYP2C9 can affect the way prescription drugs work for you.
~ CYP2C9 is also involved in the metabolism of THC from cannabis.
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CYP2C9: Breaking down prescription medications and more
Have you ever wondered why certain medications don’t work well for you? Genetic variants can change how fast or slow a medication, toxicant, or supplement is broken down and eliminated by your body.
The CYP2C9 gene is part of the CYP450 family of genes, which code for the enzymes needed for phase I detoxification.
The CYP2C9 gene codes for an enzyme that metabolizes, or breaks down, quite a few medications in the liver.
CYP2C9 also breaks down linoleic acid, arachidonic acid, and serotonin outside the liver.[ref]
Some popular prescription medications metabolized by using the CYP2C9 enzyme include:
- losartan (blood pressure)
- A complete list can be found on Pharmacy Times.
There are several genetic variants of CYP2C9 that either increase or decrease the activity level of the enzyme.
This is important when looking at how your body will respond to different doses of common drugs.
Let’s look at some examples of how the CYP2C9 variants are important:
- With some loss-of-function variants of CYP2C9, people may have an increased risk of stomach bleeding with NSAIDs.[ref]
- Celecoxib, a popular medication, is metabolized by the CYP2C9 enzyme. A new study recommends a lower starting dosage for those with reduced enzyme function.[ref]
- Warfarin is a popular prescription anticoagulant, often used after strokes or for those at risk for blood clots. Dosage variations determined by genetic factors are mainly based on the CYP2C9 and VKORC1 gene variants.
- A popularly prescribed statin, rosuvastatin, is also partially metabolized by CYP2C9. A recent study found that those with slow CYP2C9 variants had more of a reduction in LDL levels when using rosuvastatin.[ref]
- THC, the active component of cannabis, is partially metabolized by CYP2C9.[ref]
What should you do if you are a slow or fast CYP2C9 metabolizer?
Knowing how your body metabolizes different medications is important. But it is not as simple as taking more medicine if you are a slow metabolizer.
Many medications can be metabolized by using several different CYP enzymes, so your body may have a good backup route for breaking down some drugs and toxins. For example, the prescription sleep medication zolpidem is metabolized through several different CYP enzymes, including CYP2C9. However, research shows the slow CYP2C9 enzymes only matter for zolpidem in people who also have slower CYP3A4.[ref]
Some medications need to be metabolized using a CYP enzyme before they will begin to work because the metabolite is actually the drug. This type of medication is called a pro-drug since the actionable drug is formed by your body breaking down the pro-drug.
For other medications, the tablet you take is the actual drug, and the speed at which it is broken down affects how long it stays in your system.
This gets complicated (talk with your doctor):
Knowing whether you are a slow or fast metabolizer is only part of the picture. You also need to understand how the drug works and whether there are any interactions with other medications. This is one of those ‘talk with your doctor or pharmacist’ situations — especially if you are taking several prescription medications.
To add one more layer of complexity here, most studies on drug metabolism use adult study participants. In children, some medications metabolize slightly differently. For example, valproate, an epilepsy medication, mainly uses CYP2C9 in children for metabolization but not in adults.[ref]
CYP2C9 Genotype Report:
Variants in the CYP2C9 gene impact how many medications work and may alter the amount of medication you need to take.
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There are more than 50 variants of CYP2C9 that impact how the enzyme functions. Below are just a few of the more common variants — the ones that are available in 23andMe or AncestryDNA raw data.
Check your genetic data for rs1799853 (23andMe v4, v5):
- T/T: CYP2C9*2 – poor metabolizer; 40% reduction in warfarin metabolism[study]; decreased ibuprofen clearance[ref]
- C/T: One copy of CYP2C9*2, reduced activity, decreased ibuprofen clearance
- C/C: typical
Members: Your genotype for rs1799853 is —.
Check your genetic data for rs1057910 (23andMe v4, v5; AncestryDNA):
- C/C: CYP2C9*3 – poor metabolizer; 80% reduction in warfarin metabolism[study]; slower metabolism of THC (cannabis)[ref]; 2.7-fold longer half-life of celecoxib, may need altered dose[ref]; decreased ibuprofen clearance[ref]
- A/C: One copy of CYP2C9*3, reduced activity; 40% reduction in warfarin metabolism, decreased ibuprofen clearance
- A/A: typical
Members: Your genotype for rs1057910 is —.
Check your genetic data for rs2256871 (23andMe v4, v5; AncestryDNA):
- G/G: CYP2C9*9 – poor metabolizer[ref][ref]
- A/G: One copy of CYP2C9*9, decreased metabolism
- A/A: typical
Members: Your genotype for rs2256871 is —.
Check your genetic data for rs9332131 (23andMe v4, v5):
- – – or DD: CYP2C9*6 – poor metabolizer[ref]
- A/A or II: typical
Members: Your genotype for rs9332131 is —.
Check your genetic data for rs28371685 (23andMe v4, v5; AncestryDNA):
- T/T: CYP2C9*11 – poor metabolizer[study]
- C/T: One CYP2C9*11 allele, reduced activity
- C/C: typical
Members: Your genotype for rs28371685 is —.
Talk with your doctor or pharmacist if you have questions about specific prescription medications.
Check CYP2C8: For some medications, another CYP enzyme may also be able to metabolize the drug. In the case of NSAIDs and CYP2C9, the backup route of metabolism is CYP2C8. People with slow CYP2C8 and slow CYP2C9 are at a significantly increased risk of side effects from NSAIDs. If you have a genetic variant that slows the CYP2C9 enzyme, please also check your CYP2C8 variants. (Member’s data for CYP2C8 is below)
Short-term fasting may reduce CYP2C9 activity; a 36-hour fast reduced CYP2C9 activity by 19%. Keep this in mind if you are taking a medication metabolized by CYP2C9. This can affect how long the medication is active for you. For example, this could affect your clot time if you take warfarin while fasting.[ref]
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