Liver Detox Genes: CYP2C9 Genotypes and Drug Metabolism

Liver DetoxGenesThis is part of an ongoing series on the genes involved in Phase I detoxification.

CYP2C9 metabolizes quite a few popular drugs (NSAIDs, warfarin, Viagra, Prozac) in the liver as well as linoleic acid, arachidonic acid, and serotonin outside of the liver.

There are several polymorphisms in the CYP2C9 gene that change 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.  There is a neat tool put out by Stanford that estimates Warfarin dose based on genetic polymorphisms.

A popularly prescribed statin, Crestor (rosuvastatin), is also metabolized partially by CYP2C9.  A recent study found that those with slow CYP2C9 variants had an increased reduction of LDL levels when using rosuvastatin.

There is a complete list of drugs (substrates) metabolized by CYP2C9 on Wikipedia.

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:

  •  TT: CYP2C9*2 – poor metabolizer; 40% reduction in Warfarin metabolism [study]
  • CT:  One copy of CYP2C9*2, reduced activity
  •  CC: normal

 

Check your 23andMe results for rs1057910:

  • CC: CYP2C9*3 – poor metabolizer; 80% reduction in Warfarin metabolism [study]
  • AC:  One copy of CYP2C9*3, reduced activity; 40% reduction in Warfarin metabolism
  •  AA: normal

 

Check your 23andMe results for rs9332131:

  •  – -: CYP2C9*6 – poor metabolizer

 

Check your 23andMe results for rs28371685:

  • TT: CYP2C9*11 – poor metabolizer [study]
  • CT: One CYP2C9*11 allele, reduced activity
  • CC: normal

Diet and Supplements:

  • The metabolism of the Chinese medicine, Dragon’s Blood, is metabolized in part by CYP2C9.
  • Short term fasting may reduce CYP2C9 activity.
  • 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.”

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