The west side story: MEFV haplotype in Spanish FMF patients and controls, and evidence of high LD and a recombination "hot-spot" at the MEFV locus

Hum Mutat. 2004 Apr;23(4):399. doi: 10.1002/humu.9229.


Mutations at the MEFV gene cause, with various degrees of penetrance, familial Mediterranean fever (FMF). This disease is more prevalent in the Middle East than elsewhere, and most studies have focused on those populations. However, FMF occurs also in the Western Mediterranean and these populations should be taken into account for a complete view of FMF. We have analyzed intragenic MEFV SNPs in Spanish and Chueta (descendants of converted Jews) FMF patients and controls, and this constitutes the first systematic survey of normal MEFV SNP haplotype structure and variability. Our findings have allowed us to systematize the nomenclature of MEFV haplotypes and show that there is strong linkage disequilibrium (LD) at the MEFV locus and an intragenic recombination hot spot. The high local LD, regardless the recombination hot spot, is responsible for the limited diversity of the MEFV control haplotypes found in the Spanish population and it suggests that it may be a common feature to all Mediterranean populations. The MEFV mutation spectrum in Spain is quite diverse, and similar to those of France and Italy. On the contrary, the Chueta spectrum was poorer and closer to that of North African Jews, suggesting a direct connection with the Jewish diaspora.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Cytoskeletal Proteins
  • Familial Mediterranean Fever / ethnology
  • Familial Mediterranean Fever / genetics*
  • Gene Frequency
  • Haplotypes
  • Humans
  • Jews / genetics
  • Linkage Disequilibrium*
  • Mutation
  • Polymorphism, Single Nucleotide*
  • Proteins / genetics*
  • Pyrin
  • Recombination, Genetic*
  • Spain


  • Cytoskeletal Proteins
  • MEFV protein, human
  • Proteins
  • Pyrin