Establishment of the Variation of Vitamin K Status According to <i>Vkorc1</i> Point Mutations Using Rat Models

• Main Authors: Jean Valéry Debaux, Abdessalem Hammed, Brigitte Barbier, Thomas Chetot, Etienne Benoit, Sébastien Lefebvre, Virginie Lattard
• Format: Article
• Language: English
• Published: MDPI AG 2019-09-01
• Series: Nutrients
• Subjects: vitamin K epoxide reductase; vitamin K status; mutation; osteocalcin
• Online Access: https://www.mdpi.com/2072-6643/11/9/2076

Vitamin K is crucial for many physiological processes such as coagulation, energy metabolism, and arterial calcification prevention due to its involvement in the activation of several vitamin K-dependent proteins. During this activation, vitamin K is converted into vitamin K epoxide, which must be re-reduced by the VKORC1 enzyme. Various <i>VKORC1</i> mutations have been described in humans. While these mutations have been widely associated with anticoagulant resistance, their association with a modification of vitamin K status due to a modification of the enzyme efficiency has never been considered. Using animal models with different <i>Vkorc1</i> mutations receiving a standard diet or a menadione-deficient diet, we investigated this association by measuring different markers of the vitamin K status. Each mutation dramatically affected vitamin K recycling efficiency. This decrease in recycling was associated with a significant alteration of the vitamin K status, even when animals were fed a menadione-enriched diet suggesting a loss of vitamin K from the cycle due to the presence of the <i>Vkorc1</i> mutation. This change in vitamin K status resulted in clinical modifications in mutated rats only when animals receive a limited vitamin K intake totally consistent with the capacity of each strain to recycle vitamin K.