A HYPOTHETICAL ROLE FOR PLAGUE IN THE SELECTION OF MEFV MUTATION CARRIERS IN THE MEDITERRANEAN AREA
Familial Mediterranean fever (FMF) is the most common autoinflammatory disease associated with mutations in the MEFV gene encoding Pyrin. MEFV mutations are frequent in the Mediterranean region. Increased resistance to an infection endemic to this area could have caused a selective advantage for individuals with MEFV mutations. Recent studies have shown that Pyrin is a part of host defense against microorganisms and it gets activated after sensing Rho GTPase inactivation by bacteria such as Clostridium difficile or Yersinia pestis. However, Yersinia species have another effector molecule, YopM which inhibits Pyrin in addition to RhoA modifiers YopE and YopT. Continuously overactive Pyrin in individuals with MEFV mutations could be a good host defense against Yersinia infections. Y. pestis causes plague, which led to a devastating pandemic in the Mediterranean basin. Thus, plague could be the infection which caused a selective biologic advantage for MEFV mutation carriers in this area.
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