VKORC1, short for Vitamin K epoxide reductase complex subunit 1, is a key enzyme in the vitamin K cycle. It is responsible for reducing vitamin K epoxide back to its active form, which is essential for the γ -carboxylation of vitamin K-dependent proteins involved in blood coagulation [2,4]. This process is crucial for maintaining normal blood clotting function, and VKORC1 is also the molecular target of coumarins, a type of anticoagulant drug [2].

Genetic studies have shown significant associations related to VKORC1. Polymorphisms in VKORC1 play a major role in warfarin dose variation, as different ethnic groups have distinct VKORC1 genotypes, influencing warfarin requirements [1]. Mutations in VKORC1 can lead to a coumarin-resistant phenotype, and a specific SNP (rs9923231) in its promoter region is a major pharmacodynamic determinant of coumarin dose [2]. Additionally, in rodents, SNPs in vkorc1 are associated with resistance to anticoagulant rodenticides [3,6]. In humans, VKORC1 rs9923231 polymorphism may increase the risk of osteoporosis [5].

In conclusion, VKORC1 is vital for the vitamin K cycle and blood coagulation. Genetic models have revealed its role in drug response, such as warfarin dosing, and in disease conditions like osteoporosis and rodenticide resistance in rodents. Understanding VKORC1 through these models provides valuable insights into anticoagulant therapy and bone-related diseases.