What alleles represent CYP2C19 loss of function?
The CYP2C19*1 allele results in normal metabolism of clopidogrel whereas the CYP2C19*2 and CYP2C19*3 alleles, the most two common CYP2C19 loss-of-function alleles, are responsible for more than 90% cases of poor metabolism.
What is the most common increased function allele for CYP2C19?
CYP2C19*2 (rs4244285) is the most common allelic variant in Caucasians and results in aberrant splicing and loss-of-enzyme activity [8]. In contrast, the regulatory polymorphism rs12248560 defining CYP2C19*17 increases transcriptional activity and causes the ultrarapid CYP2C19 metabolism [9].
What does CYP2C19 metabolize?
CYP2C19 catalyzes the metabolism of several drugs, including proton pump inhibitors (PPIs) (e.g., omeprazole, lansoprazole, pantoprazole), antidepressants (e.g., citalopram and amitriptyline), antiplatelet drugs (e.g., clopidogrel), antifungals (e.g., voriconazole), and anticancer compounds (e.g., cyclophosphamide).
How does CYP2C19 affect metabolism?
Most often, changes in the CYP2C19 gene lead to impaired metabolism of these drugs, which reduces their effectiveness. One change in the CYP2C19 gene (known as CYP2C19*17) increases the enzyme’s ability to metabolize drugs.
What happens if CYP2C19 is inhibited?
CYP2C19 Inhibitors Drugs that inhibit CYP2C19 activity (Table 2) are likely to increase the plasma concentrations of the medications listed with an asterisk in Table 1, and in some cases adverse outcomes may occur.
What is CYP2C19 genetic testing?
CYP2C19 testing identifies 11 of the more common alleles (*2-*10,*12,*17) in PCR-multiplex format, providing increased sensitivity and quality performance. This CYP2C19 detection panel is the most extensive on the market and covers seven known poor metabolizer alleles and one known rapid metabolizer allele.
What happens when CYP2C19 is inhibited?
What does it mean to be a CYP2C19 rapid metabolizer?
Ultrarapid Metabolizer (UM) – This means there are two copies of a CYP2C19 gene with increased activity. This results in very high CYP2C19 activity. About 5 out of 100 people have this gene status. Certain drugs should be used with caution and patients may need to have their doses of some medications adjusted.
What are CYP2C19 inhibitors?
CYP2C19 catalyzes the metabolism of more than 12 clinically important drugs, such as omeprazole (antiulcerative), (S)-mephenytoin (anticonvulsant), and diazepam (anxiolytic), etc. (Lee, 2012). It plays an important role in the proton pump–inhibitor therapy for peptic ulcer and gastroesophageal reflux diseases.