The CYP2C19 gene is important in how your body responds to medications and breaks down toxins. Important here is that variants in CYP2C19 impact your individual response to medications such as omeprazole, clopidogrel, diazepam, and certain SSRIs.
The CYP family of enzymes breaks down both toxins and medications. (Learn more about other detoxification genes.)
CYP2C19: From omeprazole to clopidogrel
The CYP2C19 enzyme is responsible for the breakdown (also called metabolism) of several popular drugs, including proton pump inhibitors (omeprazole, esomeprazole, lansoprazole), certain anti-epileptics, and an antiplatelet drug (clopidogrel).
Several important CYP2C19 genetic variants impact how drugs break down, causing some people to be poor metabolizers and others to be fast metabolizers.
You can have increased side effects (depending on the medication) either from being a slow metabolizer or a fast metabolizer.
Some medications, called pro-drugs, need to break down into their metabolites for the drug to be effective. Other drugs clear your system through the use of the CYP enzymes. Thus, the effect of a variant depends on the specific medication.
CYP2C19 medication example:
Examples of interactions with CYP2C19 genetic variants:
- A CYP2C19 fast metabolizer taking omeprazole to treat h. pylori may have an insufficient response because the drug may not remain active in the body long enough.[ref]
- Alternatively, pro-drugs, such as clopidogrel, convert into their active drug state through CYP2C19. If you are a poor metabolizer, it could mean clopidogrel (an anticoagulant) isn’t activated enough, and you wouldn’t be protected from blood clots.[ref]
- Diazepam is another common drug metabolized partly by CYP2C19 (along with the CYP3A4 enzyme). Currently, there are no official recommendations to physicians as to reducing the dosages for poor metabolizers, but there is a box warning about CYP2C19.[ref]
- Some SSRIs, citalopram, sertraline, and escitalopram, also metabolize mainly through CYP2C19.[ref]
- A 2021 study showed that the average dose of citalopram is not as effective as an antidepressant for people with one copy of a non-functioning CYP2C19 variant (rs4244285).[ref]
CYP2C19 Poor Metabolizers:
Check your genetic data below to see if you are likely to be a poor metabolizer. A wide variation exists in how this gene metabolizes these drugs.
- Approximately 10 – 20% of Asians are poor metabolizers, as are 2 – 5% of people of Caucasian descent.
- Up to 20-30% of Caucasians are fast metabolizers, but less than 5% of Asians are.
Here is more information on drugs that are metabolized through CYP2C19.
In addition to drug metabolism, CYP2C19 also helps to activate and break down some hormones, such as progesterone.[ref] It is involved (minor) in metabolizing melatonin[ref] and is also involved in the metabolism of estradiol.[ref] Note that CYP2C19 is not the only route for metabolizing these hormones, just one way that the body can break them down.
CYP2C19 Genotype Report:
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CYP2C19 Poor metabolizers:
Check your genetic variants for rs4244285 681G>A (23andMe v4, v5):
- A/A: non-functioning (CYP2C19*2) (clopidogrel unlikely to work)
- A/G: poorer metabolizer
- G/G: typical[ref]
Members: Your genotype for rs4244285 is —.
Check your genetic variants for rs4986893 (23andMe v4, v5; AncestryDNA):
- A/A: poor metabolizer (CYP2C19*3), increased risk of lung cancer[ref]
- A/G: slow metabolizer
- G/G: typical[ref]
Members: Your genotype for rs4986893 is —.
CYP2C19 Ultra-fast metabolizers:
Check your genetic variants for rs12248560 (23andMe v4, v5; AncestryDNA):
- C/C: typical
- C/T: ultrafast metabolizer (CYP2C19*17), more likely to benefit from tamoxifen treatment
- T/T: ultrafast metabolizer (CYP2C19*17), more likely to benefit from tamoxifen treatment[ref]
Members: Your genotype for rs12248560 is —.
Stop smoking! If you are a CYP2C19 poor metabolizer and a smoker, you have a 5x increased risk of lung cancer[ref] and a 17x increased risk of laryngeal cancer.[ref]
Pharmacogenetic testing for antidepressants:
If you are trying to figure out whether an antidepressant will work for you, I would suggest going beyond what you can learn from your genetic raw data file, which may not cover everything. Instead, look into pharmacogenetic testing, which is a clinical test specifically looking for gene-drug interactions. Your doctor can likely order it for you, or you can order it on your own from some testing places.
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CYP3A4: Breaking down prescription meds
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Originally published July, 2018. Updated Feb. 2021.
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.