Distribution and origin of Factor V Leiden: revisited with new approach and suppositions

In this edition of “Phlebological Review” there is an interesting review article discussing the distribution of Factor V Leiden (FVL) mutation and arguing the origin of this mutation [1]. To briefly remind the reader, FVL is a missense point mutation (G1691A) in the clotting factor V (FV) gene, leading to an amino acid change in the FV molecule (Arg506Gn). FV is an important cofactor for the clotting system that prevents blood loss in cases of injuries. It is usually inactivated by activated protein C (APC) at amino acid position 506 of the FV molecule, the position that is affected by FVL. Therefore, this mutation renders FV to resist inactivation (a condition termed as APC-resistance), and this causes increased tendency towards clotting, which may be clinically manifested as venous thromboembolic disorders (VTE) with serious health issues that may be fatal [2]. Since its identification in 1993/1994 [3, 4], APC-resistance due to FVL has been found to be in high percentage of healthy individuals and patients with VTE. However, this was true in populations of Caucasian origin, but the mutation was very rare or absent in non-Caucasians [2, 5].
The confined presence of FVL in Caucasians brought speculations that the mutation might have occurred as a single event in a Caucasian ancestor. This was explored by few researchers, including the writer of these lines, who found certain single nucleotide polymorphisms (SNP) to be in linkage disequilibrium with FVL, supporting the hypothesis of a single origin in a single ancestor [6-10]. Taking the research further steps forward, researchers combined the molecular results with the geographic distribution of FVL and the available anthropological data, trying to find where and when this single ancestor might have lived. Some researchers suggested that the ancestor had lived somewhere in Europe after the Caucasoid-Mongoloid separation (around 32,000 years go), while others thought it should have happened in the East Mediterranean area or Turkey (the Near East) (about 10,000 years ago), and then moved to Europe with the migration of Neolithic farmers [2, 5].
In the article by Simka and Latacz [1], the authors propose a new interesting hypothesis on the origin of FVL. The authors present their opinion based on current available data, including molecular studies on current human samples and on archeological human remnants, geographic distribution of FVL in the Near East and Europe (including isolated ethnic...


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