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CYP2C19 is an important detox enzyme responsible for clearing approximately 10% of commonly used clinical drugs, including antidepressants (citalopram), proton pump inhibitors (omeprazole), and antiplatelet drugs (Plavix/clopidogrel). High enzyme activity has been associated with depression. Read on to find our more about CYP2C19 function, gene variants, and supplements that decrease enzyme activity.

CYP2C19

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CYP2C19 is one of the cytochrome P450 monooxygenases (CYPs). These are enzymes that eliminate most of the drugs and toxins from the human body (R).

Read more about CYPs here.

This enzyme is responsible for processing more than 25 clinically important drug groups. It clears about 10% of commonly used clinical drugs that undergo Phase I detoxification (R).

CYP2C19 Function

This enzyme metabolizes:

CYP2C19 Location

This enzyme is found in the liver. However, it is also active in the fetal brain, with a possible role in brain development (R).

CYP2C19 The Good

This enzyme participates in converting arachidonic acid to epoxyeicosatrienoic acids (EETs). EETs have beneficial effects on the heart and blood vessels.

Low enzyme activity increases the risk of heart disease (162 subjects) (R).

CYP2C19 The Bad

High CYP2C19 activity is associated with depression and smaller hippocampus volume in humans (1418 subjects) (R).

A study in Sweden shows that people with high enzyme activity (CYP2C191 carriers) are more prone to depression than those with defective enzyme function (CYP2C192 carriers) (1472 subjects) (R).

CYP2C19 deficiency is associated with a lower prevalence of major depressive disorder and lower depression severity in African-Americans (3848 subjects) (R).

Depressed suicide attempters with high enzyme activity show higher suicidality (209 subjects) (R).

Mice with high enzyme activity have impaired serotonin and BDNF production in the hippocampus (R).

CYP2C19 Gene Polymorphism

CYP_metabolizers

There are more than 30 CYP2C19 variants (R, R).

Based on the the variants they carry, individuals can be categorized as:

  • ultrarapid metabolizers (*1 /*17 or *17 /*17)
  • extensive metabolizers (*1/*1)
  • intermediate metabolizers (*1 /*2, *1 /*3, or *2 /*17)
  • poor metabolizers (*2 /*2 or *2 /*3) (R).

CYP2C19 poor metabolizers (low enzyme activity) have an increased risk of heart disease, correlated with an increase in the circulating levels of CRP in women (162 subjects) (R).

Poor metabolizers have an increased risk of side effects associated with CYP2C19-metabolized drugs like sertraline (R).

On the other hand, ultrarapid metabolizers have an increased risk of being refractory (resistant) to proton pump inhibitor (PPI) therapy (meta-analysis, 19 studies) (R).

rs424485 is also known as CYP2C19*2. This variant (A) reduces enzyme function (R).

It is present in 15% of Whites and Africans, and 29–35% of Asians (R). The highest frequency of 61% is found in Native populations from Oceania (R).

Plavix (clopidogrel) is less effective in people with this variant. Therefore, they are at higher risk of developing heart damage (559 and 523 patients) (R, R).

Also known as the CYP2C19*3, this variant (A) reduces enzyme function (R).

This variant is typically only found in Asians (2–9%) (R, R).

Plavix (clopidogrel) is less effective in people with this variant. They are at higher risk of developing heart damage (559 subjects) (R).

rs12248560 is also known as the CYP2C19*17 variant. The T in this position increases enzyme function (R).

The frequency of this variant ranges from 3–21% (R). It is more frequent in Mediterranean-South Europeans and Middle Easterns (R), and less frequent among Asians. (R)

Adults with CYP2C19*17 more often have decreased blood voriconazole levels in therapy (70 patients) (R).

This variant protects against recurrent heart damage. People with this variant have greater therapeutic responsiveness to Plavix (clopidogrel) but they have an increased risk of developing bleeding (meta-analysis, 11 studies) (R).

Decreasing CYP2C19

These decrease CYP2C19:

FDA Compliance

The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.

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  • Holly LeGros

    Just wondering if you have good info on the cyp1a1 enzyme….mine was impaired ,,,,don’t know how many sites or positions but I know it has toi do with fumes, solvents + hydrocarbons …I have been sensitive to car fumes, solvents, rubber, remodeling chemicals, mold gases + all toxins released during a remodel…I could not handle the Hashish marijuana passed around one time + had a terrible experience…..I took drugsa like amitriptylene for a very long time…seemed OK but don’t know…went off yrs ago….Also a problem with COMT++ result….mot sure what all that gene has done but your info on this gene was very good, brief + understandable…have anything on mine?? This gene you share was OK for me…. Thanks ….

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