What is the role of CYP2C9 gene in prescribing 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 the B gene?
The HLA-B gene provides instructions for making a protein that plays a critical role in the immune system. HLA-B is part of a family of genes called the human leukocyte antigen (HLA) complex.
Does warfarin inhibit CYP2C9?
Furthermore, warfarin alcohols are known to competitively inhibit CYP2C9 yet are not metabolized (15).
What is the difference between R and S warfarin?
For the anticoagulant warfarin, S-warfarin is more highly bound to albumin than R-warfarin, while overall R-warfarin is more highly protein bound than S-warfarin. S-warfarin is also 5 times more potent as a blood anticoagulant than the R-form.
What is warfarin made from?
Warfarin is derived from coumarin, a sweet-smelling anticoagulant (blood-clotting) chemical found naturally in sweet clover and many other plants. In 1954, warfarin was approved for clinical use and has remained a popular anticoagulant ever since.
What is AB allele?
Cis-AB is a rare fourth version of the blood type gene. It is an allele that gives you type AB blood all by itself! If you have the cis-AB allele, the other allele you got from your parents will not affect your blood type. No matter what it is, you will have type AB blood.
Is warfarin a cyp2c19 inhibitor?
Warfarin produces its therapeutic effect by inhibiting the action of vitamin K epoxide reductase complex 1 (VKORC1) that is necessary to produce the clotting factors II (prothrombin), VII, IX, and X. Like CYP2C9, several genetic polymorphisms of VKORC1 can alter a patient’s response to warfarin.
How does warfarin affect protein C and S?
Warfarin inhibits the body’s own production of protein C and protein S. Therefore, initial treatment with warfarin alone in people with protein C or protein S deficiency may temporarily make clotting worse or precipitate a new clot or a severe skin rash known as skin necrosis.
How are CYP2C9 and VKORC1 genotypes used to determine warfarin doses?
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 the genotype frequency of the VKORC1 polymorphism?
The VKORC1(rs 9923231, -1639 G>A) polymorphism, genotype frequencies were 20.5%, 40.5%, and 38.9% for GG, GA, and AA genotypes, respectively. The allelic frequency for VKORC1-1639 A was 60%. In the studied population the CYP2C9 *2 mutant allele frequency was found to be 12.6%.
Is there a difference between the variant alleles of vkorc1-1639 G>A and CYP2C9?
However, the comparisons among *1/*1 vs. *2/*2, *2/*3,*3/*3 (P = 0.22) and*1/*2, *1/*3 vs.*2/*2, *2/*3,*3/*3 (P = 0.54) showed no significant differences (Table 3). The simultaneous effect of the variant alleles of VKORC1-1639 G>A and CYP2C9 is shown in Figure 1.
Which genotypes are sensitive to warfarin?
Warfarin Therapy and the Genotypes CYP2C9 and VKORC1. Patients who carry the -1639G>A polymorphism in the promoter region of the VKORC1 gene are more sensitive to warfarin and require lower doses. The FDA-approved warfarin drug label provides a dosing table based on CYP2C9 and VKORC1 genotypes ( Table 1 ).