Have you ever wondered why certain medications don’t work well for you? Genetic variants can change how fast or how slow the medication is broken down in your body.
CYP2C9 is a gene that codes for an enzyme that metabolizes quite a few medications in the liver as well as linoleic acid, arachidonic acid, and serotonin outside of the liver.[ref]
Some of the most prescribed drugs metabolized with CYP2C9 include losartan (blood pressure), Warfarin, acenocoumarol, tolbutamide (Orinase), glipizide (Glucotrol), ibuprofen (Advil, Motrin), celecoxib (Celebrex), montelukast (Singulair), naproxen (Aleve). 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 is going to respond to different doses of common drugs. For example, with some loss-of-function variants of CYP2C9, people may have an increased risk of stomach bleeding with NSAIDs.[ref] Celecoxib is another drug that is metabolized by the CYP2C9 enzyme, and a new study recommends a lower starting dosage for those with reduced enzyme function.
Warfarin is a popular prescription anticoagulant, often used after strokes or for those at risk for blood clots. Dosage variations that are determined by genetic factors are mainly based on the CYP2C9 and VKORC1 gene variants.
A popularly prescribed statin, Crestor (rosuvastatin), is also partially metabolized by CYP2C9. A recent study found that those with slow CYP2C9 variants had more of a reduction of LDL levels when using rosuvastatin.
THC, the active component of marijuana, is partially metabolized by CYP2C9. [ref]
CYP2C9 Genetic Variants
While more than 50 variants of CYP2C9 have been found, a few of the more common variants that are available in 23andMe raw data are listed below.
Check your 23andMe results for rs1799853 (v4, v5):
- T/T: CYP2C9*2 – poor metabolizer; 40% reduction in Warfarin metabolism [study]
- C/T: One copy of CYP2C9*2, reduced activity
- C/C: normal
Check your 23andMe results for rs1057910 (v4, v5):
- C/C: CYP2C9*3 – poor metabolizer; 80% reduction in Warfarin metabolism [study]
- A/C: One copy of CYP2C9*3, reduced activity; 40% reduction in Warfarin metabolism
- A/A: normal
Check your 23andMe results for rs2256871 (v4, v5):
Check your 23andMe results for rs9332131 (v4, v5):
- – – or DD: CYP2C9*6 – poor metabolizer[ref]
- II: normal
Check your 23andMe results for rs28371685 (v4, v5):
- T/T: CYP2C9*11 – poor metabolizer [study]
- C/T: One CYP2C9*11 allele, reduced activity
- C/C: normal
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 that is metabolized by CYP2C9 as this can affect how long the medication is active for you. For example, this could affect your clot time if you are taking Warfarin while fasting.
Hesperitin, a flavonoid found in lemons and oranges, is an inhibitor of CYP2C9.[ref]
Quercetin interacts with warfarin dosages, but not through CYP2C9 metabolism. “Quercetin metabolites are able to strongly displace warfarin from HSA suggesting that high quercetin doses can strongly interfere with warfarin therapy. On the other hand, tested flavonoids showed no or weaker inhibition of CYP2C9 compared to warfarin, making it very unlikely that quercetin or its metabolites can significantly inhibit the CYP2C9-mediated inactivation of warfarin.”
More to read:
- Celecobix therapy and CYP2C9 Genotype — NIH book with recommendations on dosing.
- Warfarin Therapy and CYP2C9 and VKORC1 Genotypes – NIH book
- This is part of a series on the genes involved in Phase I detoxification.