Does warfarin have hereditary resistance?
Warfarin resistance can be either acquired or hereditary. Possible causes of acquired resistance include enzymatic induction of warfarin metabolism by other drugs, enhanced dietary intake of vitamin K, noncompliance with therapy and hypothyroidism.
Is warfarin affected by genetics?
Many genes are involved in the metabolism of warfarin and in determining the drug’s effects in the body. Certain common changes (polymorphisms) in the CYP2C9 and VKORC1 genes account for most of the variation in warfarin metabolism due to genetic factors.
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 VKOR mutation?
Mutations in the VKORC1 gene causes generalized defective vitamin K-dependent clotting factors (VKCFD2) and warfarin resistance (WR). More detailed pharmacogenetic studies have demonstrated a strong association between single nucleotide polymorphisms (SNPs) in the VKORC1 gene and the requirement of warfarin dosage.
What is warfarin resistance usually caused by?
The most common cause of warfarin resistance is non- compliance. Others include poor absorption, high vitamin K intake, hypersensitivity to vitamin K, and rapid drug deactivation. Patient education is necessary to improve compliance and to mitigate adverse effects of warfarin therapy, regardless of the dose.
What causes warfarin to stop working?
Warfarin may not be working well if you eat certain foods that contain high amounts of vitamin K. These foods include leafy greens like kale, spinach, Swiss chard, and collards. Supplements like omega-3 fatty acids may also cause issues with warfarin.
What are the genetic factors that affect warfarin dosing?
The most important genes consistently affecting warfarin dose among different populations are the CYP2C9- a gene coding for cytochrome P450 2C9 enzyme which metabolizes the more potent S enantiomer of warfarin, and VKORC1- a gene coding for the vitamin K epoxide reductase which is an enzyme inhibited by warfarin [9, 10 …
Which medication can require higher doses because of hereditary resistance?
Warfarin resistance is a condition in which individuals have a high tolerance for the drug warfarin.
Does everyone have CYP2C9?
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 reported.
What is CYP2D6 gene?
CYP2D6 Gene – Cytochrome P450 Family 2 Subfamily D Member 6 This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids.
What is the VKORC1 gene?
The VKORC1 gene provides instructions for making a vitamin K epoxide reductase enzyme. The VKORC1 enzyme is made primarily in the liver. It spans the membrane of a cellular structure called the endoplasmic reticulum, which is involved with protein processing and transport.
How does a mutation of VKORC1 affect the sensitivity of warfarin?
Warfarin targets VKORC1, an enzyme involved in vitamin K recycling. A common variant, VKORC1, c. -1639G>A, is associated with an increased sensitivity to warfarin and lower dose requirements. The CYP2C9 enzyme metabolizes warfarin and the variants CYP2C9*2 and *3, are also associated with lower dose requirements.