The population genetics of familial mediterranean fever: a meta-analysis study

Ann Hum Genet. 2008 Nov;72(Pt 6):752-61. doi: 10.1111/j.1469-1809.2008.00471.x. Epub 2008 Aug 6.


Our aim was to construct a Familial Mediterranean Fever (FMF) cumulative database and to propose a MEFV based phylogenetic tree. Data were collected from published studies. A meta-analysis based on 16,756 chromosomes from FMF patients and normal individuals from 14 affected populations was performed. Arlequin 2.0 and Phylip 3.2 software were used for population genetics analysis and phylogenetic tree construction. We have shown that MEFV mutations are distributed non-uniformly along the Mediterranean Sea area. The most frequent mutations detected in FMF patients are M694V (39.6%), V726A (13.9%), M680I (11.4%), E148Q (3.4%), and M694I (2.9%), while 28.8% of chromosomes carry unidentified or no mutations, especially in Western Europeans. The mean overall carrier rate is 0.186 with peak values in Arabs, Armenians, Jews, and Turks. Only V726A obeys the Hardy-Weinberg law in FMF patients implying that this mutation is the most ancient. Jews present the most intense genetic isolation and drift; thus they might have nested de novo mutations and accelerated evolution. Besides Jews, three population groups might follow distinct evolutionary lines (Asia Minor, Eastern European, and Western European). In conclusion, the MEFV mutation pattern is non-uniform regarding distribution, phenotypic expression, neutrality and population genetics characteristics. Jews are the candidate population for founder effects in MEFV.

Publication types

  • Meta-Analysis

MeSH terms

  • Amino Acid Substitution
  • Cytoskeletal Proteins / genetics*
  • Familial Mediterranean Fever / ethnology*
  • Familial Mediterranean Fever / genetics*
  • Genetics, Population
  • Jews / genetics
  • Mediterranean Region
  • Mutation
  • Pyrin


  • Cytoskeletal Proteins
  • Pyrin