Vitamin K (VKORC1)
VKORC1 · CYP4F2
Vitamin K is recycled in the body so it can activate clotting factors and bone proteins. The enzyme VKORC1 governs this recycling; together with CYP4F2 it largely determines how much warfarin a person needs. Vitamin K is therefore less a level topic than a pharmacogenetic one.
The markers
VKORC1 (vitamin K epoxide reductase) regenerates the reduced, active form of vitamin K after each clotting step. Common regulatory variants (marked by rs9923231 or the haplotype rs8050894) lower VKORC1 expression; carriers need markedly less warfarin because the drug inhibits exactly this enzyme. In multivariate analysis VKORC1 explained about 30 percent of the variability in warfarin requirement, CYP2C9 a further roughly 8 percent (Veenstra 2005). CYP4F2 (rs2108622) breaks down excess vitamin K and shifts the requirement upward as well.
What it means
For healthy people without anticoagulation the VKORC1 genotype has little everyday significance; vitamin K status depends mainly on diet and gut flora. It becomes clinically important during warfarin therapy: genotype-guided starting doses can speed up dosing. The pharmacogenetics page covers this aspect in depth.
Context
The VKORC1 to warfarin link is very well documented and one of the clearest pharmacogenetic effects of all. Genome shows the markers as technical evidence; a dosing decision belongs in a physician's hands.
What Genome measures. The genotypes at rs8050894 / rs9923231 (VKORC1) and rs2108622 (CYP4F2).
Related topics
Sources
- 1Veenstra et al., 2005 Association of VKORC1 variants with warfarin dose in a Hong Kong Chinese patient population. Pharmacogenetics and Genomics 15:687–691. doi.org/10.1097/01.fpc.0000174789.77614.68