What Is The Function Of CYP2C19 Gene?
Cytochrome P450 2C19 (CYP2C19) is an enzyme protein produced in the liver. This enzyme helps in the metabolism of several important drugs in the body.
It is a part of the Cytochromes P450 (CYPs) superfamily of enzymes. These enzymes all play a role in breaking down and clearing various compounds like fatty acids, drugs, steroids, and hormones.Â
CYP2C19 enzymes make up to 3% of all the CYPs produced in the liver.Â
The CYP2C19 gene (Cytochrome P450 2C19 gene) controls the production of the enzyme with the same name.Â
Did You Know? Your genes regulate drug-metabolizing enzymes, drug targets, and other proteins related to the action of drugs. Each individual has a unique genetic makeup. Hence, they might respond differently to certain medications. Learn more:
Some Important Drugs The CYP2C19 Enzyme Metabolizes
- Benzodiazepine (antidepressant drug)
- Mephenytoin (anticonvulsant drug)
- Proton Pump Inhibitors drugs (PPIs) (used to reduce stomach acid production)
- Clopidogrel (antiplatelt drug)
- Omeprazole (peptic ulcer treating drug)
- Mephenytoin (antiseizure drug)
- Proguanil (antimalarial drug)
- Diazepam (antianxiety drug)
- Voriconazole (antifungal drug)
- Cyclophosphamide (anticancer drug)
Pharmacogenomics of CYP2C19 – How Many Types Of This Gene Exist?
Pharmacogenomics studies how a person’s gene makeup affects their response to drugs.
Many changes in the CYP2C19 gene influence the enzyme’s ability to metabolize drugs.
The following are some of the most significant variations of this gene. These are called tier I variants.
| Gene variant | Also called | Effect |
| CYP2C19*1 | Wild Type | Normal enzyme activity |
| CYP2C19*2 | Loss of function allele | Reduced enzyme activity |
| CYP2C19*3 | Loss of function allele | Reduced enzyme activity |
| CYP2C19*17 | Gain of function allele | Increased enzyme activity |
Few other extended gene variations also exist.
The following are called tier II variants and are not very common. All of them lead to lowered enzyme activities.
- CYP2C19*4
- CYP2C19*4A
- CYP2C19*4B
- CYP2C19*5
- CYP2C19*6
- CYP2C19*7
- CYP2C19*8
- CYP2C19*9
- CYP2C19*10
- CYP2C19*35
CYP2C19: Metabolizer Types
The ability of the body to metabolize a drug will depend on the gene variation the person has.
There are five common types of metabolizers identified.
| Metabolizer Type | Enzyme activity | Genetic variants |
| Ultrarapid Metabolizers (UM) | Very high | *17/*17 |
| Rapid Metabolizers (RM) | High | *1/*17 |
| Normal Metabolizers (NM) | Normal | *1/*1 |
| Intermediate Metabolizers (IM) | Lower than normal | *1/*2, *1/*3, *2/*17, *3/*17 |
| Poor Metabolizers (PM) | Low | *2/*2, *3/*3/ *2/*3 |
What Does It Mean To Be A Rapid Metabolizer Of CYP2C19?
If you are a rapid metabolizer, you have higher-than-normal levels of CYP2C19 enzyme activity.
When the enzyme metabolizes a drug, you may have lower or higher drug activity depending on whether it clears the drug or converts it into an active form.
Who Is A CYP2C19 Poor Metabolizer?
If you are a poor metabolizer, your body experiences lower-than-normal CYP2C19 enzyme activity.Â
Depending on whether the enzyme clears the drug or converts it into an active form, you may have higher or lower drug activity in the body.
CYP2C19 Genetic Test
CYP2C19 genetic testing is a scientific way to understand what kind of metabolizer you are.
When it comes to certain drugs, poor metabolizers may have up to 13 times more drug exposure than rapid metabolizers. This can lead to drug toxicity and increased risk of side effects.
Individuals prescribed CYP2C19-metabolized drugs for the long term may benefit from genetic testing before fixing the dosages.
Genetic testing may help alter dosages so the side effects are minimal and the drug effect is high.
Clopidogrel Resistance and CYP2C19 Gene
One of the most popular drugs metabolized by this enzyme is clopidogrel.
This antiplatelet medicine prevents the risk of developing clots in people with existing cardiac conditions.
The CYP2C19 enzyme converts clopidogrel into its active metabolite form to work in the body.
Clopidogrel resistance is a condition caused by the lower-than-normal effectiveness of the drug when used in certain treatments.
A 2020 meta-analysis concludes that the CYP2C19*2 gene variant may be strongly associated with clopidogrel resistance.
This study further reports that the A allele in the CYP2C19*2 gene may cause clopidogrel resistance, especially in the Asian population.
Summary
- The CYP2C19 gene contains instructions to produce an enzyme with the same name. This enzyme helps metabolize important drugs like clopidogrel, omeprazole, benzodiazepine, and mephenytoin.
- Different variations of the CYP2C19 gene affect enzyme production and how drugs are metabolized in the body.
- Depending on the genetic variant present, there can be five types of CYP2C19 metabolizers – ultrarapid, rapid, normal, intermediate, and poor.
- Ultrarapid metabolizers have higher than normal and poor metabolizers have lower than normal CYP2C19 enzyme activities.
- CYP2C19 genetic testing will help understand what kind of metabolizer a person is. This may help plan drug dosages more precisely and prevent extreme side effects of a drug.
- A allele in the CYP2C19*2 gene is associated with clopidogrel resistance. For people with this allele, the drug may show reduced effectiveness.
