What is CYP2C9 polymorphism?
CYP2C9 is highly polymorphic, with a total of 61 alleles reported, all of which have either reduced or no enzymatic activity. 21. A patient’s phenotype is calculated based on the genotype of the CYP2C9 allele, its heterozygosity or homozygosity (also referred to as diplotype).
What drugs are affected by CYP2C9?
About 100 therapeutic drugs are metabolized by CYP2C9, including drugs with a narrow therapeutic index such as warfarin and phenytoin, and other routinely prescribed drugs such as acenocoumarol, tolbutamide, losartan, glipizide, and some nonsteroidal anti-inflammatory drugs.
What is genetic polymorphism in drugs?
Abstract. One of the major causes of interindividual variation of drug effects is genetic variation of drug metabolism. Genetic polymorphisms of drug-metabolizing enzymes give rise to distinct subgroups in the population that differ in their ability to perform certain drug biotransformation reactions.
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 are the effects of polymorphism in CYP2C9?
Polymorphisms in CYP2C9 have the potential to affect the toxicity of CYP2C9 drugs with somewhat lower therapeutic indices such as warfarin, phenytoin, and certain antidiabetic drugs. CYP2C9 is one of the clinically significant drug metabolising enzymes that demonstrates genetic variants with significant phenotype and clinical outcomes.
Which is genetic polymorphism of the human cytochrome P450 2C9 gene?
Genetic polymorphism of the human cytochrome P450 2C9 gene and its clinical significance. Human cytochrome P450 2C9 (CYP2C9) accounts for approximately 20% of total hepatic CYP content and metabolizes approximately 15% clinically used drugs including S-warfarin, tolbutamide, phenytoin, losartan, diclofenac, and celecoxib.
Who are the carriers of the CYP2C9 gene?
CYP2C9*2 is frequent among Caucasians with approximately 1% of the population being homozygous carriers and 22% heterozygous. The corresponding figures for the CYP2C9*3 allele are 0.4% and 15%, respectively. Worldwide, a number of other variants have also to be considered.
What is the activity score of CYP2C9 1?
For example, the wild-type CYP2C9*1 allele has been assigned an activity score of 1, CYP2C9 alleles (e.g., CYP2C9*2) that cause a decrease in enzyme function are assigned an activity score of 0.5, and alleles (e.g., CYP2C9*3) with complete loss of enzyme activity have a score of 0.