What does VKORC1 gene do?
The VKORC1 enzyme helps turn on (activate) clotting proteins in the pathway that forms blood clots. Specifically, the VKORC1 enzyme converts one form of vitamin K into a different form of vitamin K that assists in activating clotting proteins.
How does a mutation of VKORC1 affect the sensitivity of warfarin?
VKORC1 TT: warfarin The genetic variation results in increased sensitivity to warfarin. This results in an increase in the risk of excessively severe inhibition of blood clotting (INR >4) during the first month of the treatment. Recommendation: 1.
What is the chromosomal location of the VKORC1 gene?
In the liver, warfarin targets the vitamin K epoxide reductase complex subunit 1 encoded by the VKORC1 gene located on chromosome 16p11.
How does CYP2C9 affect 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.
Can you become resistant to warfarin?
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.
Which medication will be affected by single nucleotide polymorphisms in VKORC1?
Polymorphisms in the VKORC1 gene are strongly associated with warfarin dosage requirements in patients receiving anticoagulation. Revised 2006 Mar 16; Accepted 2006 Mar 30.
What causes warfarin sensitivity?
Several CYP2C9 gene polymorphisms decrease the activity of the CYP2C9 enzyme and slow the body’s metabolism of warfarin. As a result, the drug remains active in the body for a longer period of time, leading to warfarin sensitivity. The VKORC1 gene provides instructions for making a vitamin K epoxide reductase enzyme.
What increases warfarin sensitivity?
Increased sensitivity to warfarin anticoagulation is usually attributed to liver disease, vitamin K deficiency, or drug interactions.
What does vitamin K epoxide reductase do?
Vitamin K epoxide reductase (VKOR) is an integral membrane protein that catalyzes the reduction of vitamin K 2,3-epoxide and vitamin K to vitamin K hydroquinone, a cofactor required for the gamma-glutamyl carboxylation reaction.
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 is the mechanism of action of warfarin?
Warfarin competitively inhibits the vitamin K epoxide reductase complex 1 (VKORC1), which is an essential enzyme for activating the vitamin K available in the body. Through this mechanism, warfarin can deplete functional vitamin K reserves and therefore reduce the synthesis of active clotting factors.
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.