What is CYP2C9 gene?
The CYP2C9 gene provides instructions for making an enzyme that is found in a cell structure called the endoplasmic reticulum, which is involved in protein processing and transport. The CYP2C9 enzyme breaks down (metabolizes) compounds including steroid hormones and fatty acids.
What does CYP2C9 do to warfarin?
A patient’s CYP2C9 and VKORC1 genotype can be used to help determine the optimal starting dose of warfarin. The CYP2C9 gene encodes one of the main enzymes involved in the metabolism of warfarin. Several variant CYP2C9 alleles are associated with reduced enzyme activity and lower clearance rates of warfarin.
What is cytochrome P450 enzyme CYP2C9?
Cytochrome P450 family 2 subfamily C member 9 (abbreviated CYP2C9) is an enzyme protein. The enzyme is involved in metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, the protein is encoded by the CYP2C9 gene.
Which drugs are metabolised by CYP2C9?
Cytochrome P450 2C9 (CYP2C9) is one of the most abundant CYP enzymes in the human liver. CYP2C9 metabolizes more than 100 therapeutic drugs, including tolbutamide, glyburide, diclofenac, celecoxib, torasemide, phenytoin losartan, and S-warfarin).
Is CYP2C9 polymorphic?
CYP2C9 is highly polymorphic, with a total of 61 alleles reported, all of which have either reduced or no enzymatic activity. A patient’s phenotype is calculated based on the genotype of the CYP2C9 allele, its heterozygosity or homozygosity (also referred to as diplotype).
Why is warfarin given?
About warfarin This means your blood will be less likely to make a dangerous blood clot. Warfarin is used to treat people who have had a previous blood clot, such as: a blood clot in the leg (deep vein thrombosis, or DVT) a blood clot in the lungs (pulmonary embolism)
What does polymorphic mean in biology?
Polymorphism = Polymorphism involves one of two or more variants of a particular DNA sequence. The most common type of polymorphism involves variation at a single base pair. Polymorphisms can also be much larger in size and involve long stretches of DNA.
Where is the CYP2C9 gene located on the chromosome?
The CYP2C9 gene is located on chromosome 10q24.1, and approximately 60 CYP2C9 alleles have been described, as detailed in Chapter 1. The CYP2C9∗2 and ∗3 alleles are the most extensively studied and result from variants in the coding regions of the gene, as shown in Table 6.3.
Which is the most well characterized CYP2C9 alleles?
The two most well-characterized variant alleles are CYP2C9*2 (NM_000771.3:c.430C>T, p.Arg144Cys, rs1799853) and CYP2C9*3 (NM_000771.3:c.1075A>C, p. Ile359Leu, rs1057910), causing reductions in enzyme activity of 30% and 80%, respectively. On the basis of their ability to metabolize CYP2C9 substrates, individuals can be categorized by groups.
How many polymorphisms are there for the enzyme CYP2C9?
More than 33 polymorphisms of the gene encoding CYP2C9 enzyme have been reported (∗1B through to ∗34), but most common variants are CYP2C9∗2 (5.5-fold decreased activity) and CYP2C9∗3 (27-fold decreased activity) alleles that produce enzyme with significantly reduced activity. Homozygous for CYP2C9∗3 are PMs.
How are CYP2C9 mutations related to drug reactions?
Multiple in vivo studies also show that several mutant CYP2C9 genotypes are associated with significant reduction of in metabolism and daily dose requirements of selected CYP2C9 substrate. In fact, adverse drug reactions (ADRs) often result from unanticipated changes in CYP2C9 enzyme activity secondary to genetic polymorphisms.