The enzyme VKORC1 (full name: Vitamin K epoxide reductase complex 1) is involved in the activation of vitamin K, a vitamin that in turn plays a role in blood clotting.
A deficiency of vitamin K can impair some clotting processes, as a result of which haemorrhages can occur. Controlled use is made of this mechanism to prevent thrombosis: inhibiting the enzyme VKORC1, with the help of blood thinners, results in clots developing in the blood vessels less quickly.
The enzyme CYP2C9 (full name: Cytochrome P450 2C9) is involved in the metabolisation of various drugs, including the coumarin-like blood thinner warfarin.
An abnormal CYP2C9 metabolism may influence the availability of this drug and therefore also have an impact on blood clotting.
Genetic predisposition
Your individual risk of side effects in the event of treatment with the coumarin-like blood thinners acenocoumarol, phenprocoumon and warfarin may be partly explained by genetic variations. For example, it is known that mutations in the VKORC1 gene and CYP2C9 gene can reduce enzyme activity. As anticoagulants need to be dosed precisely, it may be important to know what genotype you have.
When a genotype is determined variations are indicated by two so-called alleles. Each allele has a name consisting of an asterisk (*) and a number.
People with a VKORC1*2 allele have reduced enzyme activity and consequently exhibit increased sensitivity to coumarin-like blood thinners.
People with the VKORC1*2/*2 genotype show a more significant reduction in enzyme activity than those with VKORC1*1/*2. The genotype VKORC1*2/*2 is found in around 15% of the European population and VKORC1*1/*2 in around 45%.
The enzyme CYP2C9 also has an impact on the breakdown of the coumarin-like blood thinner warfarin. The guideline for acenocoumarol and phenprocoumon was amended in mid-2019, so that CYP2C9 is no longer included in the dose recommendation.
People with a divergent CYP2C9 genotype (*2 and *3) have reduced enzyme activity and consequently exhibit increased sensitivity.
Roughly 35% of Europeans have such an abnormal variant.