Cytochrome CYP2C9 is an enzyme of the hepatic cytochrome P450 family, whose main function is the metabolism of xenobiotics. Its substrates include multiple widely used anti-inflammatory drugs, so variants in this gene impact the metabolism of many common drugs.
Metabolizer profile CYP2C9
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. CYP2C9 are mainly found in the liver, but can be found in other tissues such as duodenum or small intestine.
Cytochrome CYP2C9 is a member of this enzyme family and, together with CYP2C19, can account for up to 20% of its total activity. It is involved in the metabolism of a multitude of xenobiotics including commonly prescribed drugs such as non-steroidal anti-inflammatory drugs (ibuprofen, diclofenac, celecoxib), antiepileptics (such as phenytoin) or anticoagulants (such as warfarin), among many others.
In addition to the above, CYP2C9 is also involved in the biotransformation of other xenobiotics such as environmental and industrial pollutants, although in a much less significant way. Like other enzymes of the same family, CYP2C9 is also involved in the biosynthesis of melatonin, cholesterol, steroids and other lipids.
This gene is highly polymorphic and loss or decrease of function alleles can be found, which influences not only the ability to metabolize the drugs described above, but also the risk of possible adverse effects.
It is important to bear in mind that, independently of the effects on the activity that the different genotypes may have, there are multiple drugs and foods (such as St. John's wort or soy) that can act as inhibitors or inducers and that significantly affect their function. This is important, above all, in polytherapy because it can condition the therapeutic effect and the presence of side effects of drugs metabolized by CYP2C9.
Genes analyzed
Bibliography
Rendic S, Guengerich FP. Contributions of human enzymes in carcinogen metabolism. Chem Res Toxicol. 2012 Jul 16;25(7):1316-83.
Katherine N et al. Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2C9 and Nonsteroidal Anti-Inflammatory Drugs. Clinical Pharmacology & TherapeuticsVolume 108, Issue 2.
Pharmacogenomics Knowledgebase (PharmGKB). Gene-specific Information Tables for CYP2C9.
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.