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By Gerald Litwack

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Screening for VKORC1 polymorphisms that affect warfarin dosage could be helpful to tailor dosage at the onset of oral anticoagulant treatment in order to lower thrombosis and bleeding risks. ß 2008 Elsevier Inc. 1016/S0083-6729(07)00002-7 # 2008 Elsevier Inc. All rights reserved. 23 24 Andrea A. Garcia and Pieter H. Reitsma I. Vitamin K Cycle: Limiting Step of Carboxylation Vitamin K-dependent proteins require carboxylation of key glutamic acid residues for exerting their activity. The best known vitamin K-dependent proteins include the coagulation factors II (prothrombin), VII, IX, X, protein Z, protein S, and protein C.

2004). , 1999). Due to its dependency on adequate g-carboxylation of glutamate residues for full functionality, acquired deficiency of MGP, especially through prenatal exposure to coumarins, can result in a phenotype similar to Keutel syndrome. C. Vitamin K and osteoporosis The interaction between dietary vitamin K intake and bone health has been investigated in several epidemiological and interventional studies.

In the first place, this discovery is giving us detailed insight in the biochemical pathway involved in vitamin K cycling, including the putative role of PDI. In addition, the discovery of the VKORC1 gene was important for understanding the wide variability in the individual response to vitamin K antagonists like warfarin. Several studies have shown that the activity of the VKORC1 enzyme is determined by genetic variants, which helps to explain interindividual and also interethnic differences in therapeutic response to coumarin drugs.

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