Clinical, Molecular, and Bioinformatic Study of Common Thrombophilia Mutation Factor V Leiden

The most common genetic cause associated with thrombophilia is Leiden mutation (G1691A) of the coagulation factor V (F5) gene.

Data collected anonymously from 355 unrelated Greeks examined for the above mutation were analyzed. Bioinformatic investigation was conducted for factor V, including phylogenetic analysis, genetic network analysis, and 3D modeling of wild-type and Leiden protein.

Analysis confirmed the importance of F5 Leiden in thrombosis and the significance of a positive family history of thrombosis. In silico analysis of the F5 Leiden revealed a linkage between mammalian species and a potential functional interaction of F5 with 25 other genes, several of which have been associated with cardiovascular diseases. 3D modeling revealed that the Leiden mutation confers an H-bond network alteration in the functional region of FV, resulting in a hypercoagulable state.

This study highlighted the great value of a positive family history of thrombosis and the importance of testing for this common mutation as prevention strategy components for thrombophilia, including thrombotic brain aneurysms. Bioinformatic analysis indicated the importance of the Leiden mutation in protein structure and function. The findings of this study increase understanding of molecular and clinical features of thrombophilia and may eventually lead to better prevention of thrombosis.