The Black Death ravaging Europe in the fourteenth century might be the pathogen-driven selective pressure for factor V Leiden

Abstract

Factor V Leiden as a mutant gene defect of hereditary thrombophilia exists peculiarly in Caucasians but almost absent in people traditionally living in Asia. This lopsided dispensation has persisted as an enigma to be solved. Thus, a hypothesis is raised here that the Black Death, a plague pandemic caused by Yersinia pestis, which ravaged Europe in the fourteenth century and brought on a severe human extermination constituted the pathogenic selective pressure for factor V Leiden of which the procoagulative, anti-fibrinlolysis function, and the resultant resistance potential to Yersinia pestis infection have been demonstrated in a series of animal experiments and clinical observation. The same explanation is also proposed for a similar unbalanced distribution of prothrombin G20210A mutation, another thrombophilia genetic variant, between Caucasians and Asians despite awaiting more solid evidence in the near future. On the other hand, the fact that deficiency of protein C, protein S, and antithrombin had not risen during the plague disaster is theoretically attributed to more severe and fatal disseminated intravascular coagulation associated with the dysfunction of them. The whole assumption implies an underlying evolutionary advantage of factor V Leiden and a mysterious relationship between genetic traits and diseases. It is hoped that future investigations dedicating to analysis of ancient DNA from human remains in the medieval cemeteries before, during, and after the plague will finally let the speculation come true.