The CYP (cytochrome) family of genes codes for a number of different enzymes that interact with prescription drugs. This family of enzymes is important in breaking down medications in a process known as phase I detoxification. Genetic variants that alter the way that these enzymes work can impact your reaction to a medication.
CYP2C8: From Ibuprofen to arachidonic acid
The CYP2C8 gene is important in the metabolism of several chemotherapy drugs (e.g. Taxol) as well as playing a role in the metabolism of NSAIDs.
Medications that are mainly metabolized by CYP2C8 include[ref]:
- All-trans-retinoic acid
- Ibuprofen (along with CYP2C9)
- Tenoxicam (along with CYP2C9)
A database of pharmacological and genetic interactions has information on the CYP2C8 variants and response to tacrolimus, montelukast, rosiglitazone, and pioglitazone.
Supplements such as quercetin can inhibit the CYP2C8 enzyme. [ref]
Why do we have the CYP2C8 enzyme?
We don’t have the CYP enzymes in the body just to break down new-fangled prescription drugs. In addition to pharmaceutical drugs, CYP2C8 also metabolizes arachidonic acid in the body, which is important in blood pressure regulation. This may also be important in oxidative stress in the cell. [ref ]
The metabolism of arachidonic acid by CYP2C8 is also important in eye health in aging.
Hypoxia, or low oxygen, increases CYP2C8, which in turn causes more of the conversion of arachidonic acid into epoxyeicosatrienoic acids (EETs). The increased EETs then promote abnormal vascular development in the retina of the eye.
Additionally, the increased CYP2C8 also interacted with omega-3 fatty acids, also promoting abnormal vascular development with higher levels of DHA in low oxygen conditions.[ref ]
Inhibiting CYP2C8 has been shown in studies to decrease the pathological effects in the eye from increased vascular development. This could be important in age-related macular degeneration and diabetic retinopathy.[ref] Please keep in mind that you don’t want to inhibit CYP2C8 if you are on a prescription medication that relies on the enzyme.
Genetic Variants in CYP2C8:
Check your genetic data for rs10509681 (23andMe v4, v5; AncestryDNA):
- C/C: CYP2C8*3, decreased enzyme function[ref]; ibuprofen takes longer to be metabolized[ref ]; increased risk of GI bleeding with NSAIDs[ref ], increased risk of neuropathy in breast cancer patients treated with paclitaxel[ref ]
- C/T: one copy of CYP2C8*3, decreased enzyme function; increased risk of GI bleeding with NSAIDs
- T/T: normal
Members: Your genotype for rs10509681 is —.
Check your genetic data for rs11572103 (23andMe v4, v5; AncestryDNA):
- A/A: CYP2C8*2; decreased enzyme function[ref ]
- A/T: one copy of CYP2C8*2; decreased enzyme function[ref ]
- T/T: normal
Members: Your genotype for rs11572103 is —.
Check your genetic data for rs1058930 (23andme v4, v5; AncestryDNA):
- C/C: CYP2C8*4; slightly decreased enzyme function[ref]
- C/G: one copy of CYP2C8*4; slightly decreased enzyme function
- G/G: normal
Members: Your genotype for rs1058930 is —.
Check your genetic data for rs7909236 (23andMe v4; AncestryDNA):
- T/T: CYP2C8*1B; increased enzyme activity[ref] increased risk of hypertension[ref]
- G/T: one copy of CYP2C8*1B; increased enzyme activity[ref]
- G/G: normal
Members: Your genotype for rs7909236 is —.
If you carry the CYP2C8*3 variant and take a lot of NSAIDs, you should talk with your doctor about the increased risk of GI bleeds. Be sure to also check out your CYP2C9 genetic variants. The combination of low function in both CYP2C8 and CYP2C9 increases the risk of problems from ibuprofen.
Quercetin, a flavonoid that is often used as an anti-inflammatory supplement, is an inhibitor of CYP2C8.[ref] If you carry a genetic variant that slows CYP2C8, taking quercetin along with a medication that uses CYP2C8 could cause the medication not to work appropriately.
Eye Health: Circling back around to the information above on how upregulation of CYP2C8 could increase problems with the retina, such as macular degeneration or diabetic retinopathy… Quercetin, an inhibitor of CYP2C8, has been shown to protect the eye from damage from diabetic retinopathy in animal studies.[ref] This may be something to consider if on a diet that is high in the long-chain omega-6 or omega-3 fatty acids (arachadonic acid), especially if AMD or diabetic retinopathy is a concern. Check out your genetic variants for age-related macular degeneration.