Cytochrome CYP2C19 is an enzyme of the hepatic cytochrome P450 family, whose main function is the metabolism of xenobiotics. Its substrates include multiple drugs, such as antidepressants and proton pump inhibitors, among others, so variants in this gene impact the metabolism of many common drugs.
Metabolizer profile CYP2C19
CYP P450 is a superfamily of enzymes involved in enzymatic oxidation of steroids, fatty acids, xenobiotics and other biosynthetic pathways. These enzymes convert xenobiotics into water-soluble derivatives to facilitate their excretion. They are mainly found in the liver, but can be found in other tissues.
Cytochrome CYP2C19 is a member of this family of enzymes and can account for up to 20% of their total activity. It is involved in the metabolism of a multitude of commonly prescribed drugs, such as proton pump inhibitors (e.g., lansoprazole, lansoprazole, lansoprazole).lansoprazole, omeprazole and pantoprazole), antidepressants and mood stabilizers (clomipramine, citalopram, escitalopram, sertraline or doxepin), antiplatelet drugs (clopidogrel) or antifungals (voriconazole). In addition, it is also involved in the metabolism of cholesterol, steroids and other lipids.
In addition to the above, CYP2C19 also possesses epoxygenase activity so that it metabolizes certain polyunsaturated fatty acids to form epoxide products with biological functions. It is suggested that these compounds have anti-inflammatory properties and may act as vasodilators.
This gene is highly polymorphic and loss, decrease or gain of function alleles can be found, which influences not only the ability to metabolize the drugs described above but also other biological processes such as vascular tone or inflammation.
It is important to bear in mind that, independently of the effects on activity that the different genotypes may have, there are various drugs or supplements (such as St. John's wort) that can act as inhibitors or inducers and that significantly affect cytochrome function. Therefore, the simultaneous consumption of interacting compounds can condition the therapeutic effect and the presence of side effects of drugs metabolized by CYP2C19.
Genes analyzed
Bibliography
Akasaka T, et al. CYP2C19 variants and epoxyeicosatrienoic acids in patients with microvascular angina. Int J Cardiol Heart Vasc. 2017 Apr 12;15:15-20.
Elfaki I, Mir R, Almutairi FM, Duhier FMA. Cytochrome P450: Polymorphisms and Roles in Cancer, Diabetes and Atherosclerosis. Asian Pac J Cancer Prev. 2018 Aug 24;19(8):2057-2070.
Lima JJ, Thomas CD, Barbarino J, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing. Clin Pharmacol Ther. 2021 Jun;109(6):1417-1423.
Bousman CA, Stevenson JM, Ramsey LB, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A Genotypes and Serotonin Reuptake Inhibitor Antidepressants. Clin Pharmacol Ther. 2023 Jul;114(1):51-68.
Pharmacogenomics Knowledgebase (PharmGKB). Gene-specific Information Tables for CYP2C19.