The contribution of genotypes at the MICA gene triplet repeat polymorphisms and MEFV mutations to amyloidosis and course of the disease in the patients with familial Mediterranean fever

Rheumatol Int. 2007 Apr;27(6):545-51. doi: 10.1007/s00296-006-0255-8. Epub 2006 Nov 11.


Objective: To evaluate the effects of MEFV genotypes and the major histocompatibility complex class I chain-related gene A (MICA) triplet repeat polymorphism on the severity and clinical features of familial Mediterranean fever (FMF) and amyloidosis in a group of Turkish FMF patients.

Methods: We evaluated 105 adult FMF patients (with or without amyloidosis, 33 and 72, respectively) along with 107 healthy controls who were neither related to the patients nor had a family history of FMF or Behcet's disease. After recording the demographic and clinical data, the predominant mutations in the MEFV gene locus (M694V, M680I, V726A, M694I, and E148Q) were investigated by direct sequencing. MICA transmembrane polymorphisms in exon 5 were studied by vertical gel electrophoresis and fragment analysis of the amplicons obtained from MICA locus with appropriate primers.

Results: Earlier age at onset, increased frequency of attacks, arthritis attacks, erysipelas-like erythema, increased severity scores and amyloidosis were significantly more common in M694V homozygous patients compared to the patients not M694V homozygous (P = 0.005, OR 4.55; P = 0.001, OR 7.60; P = 0.003, OR 4.57; P = 0.002, OR 7.58; P = 0.004, OR 5.15 and P = 0.018, OR 3.33, respectively). We did not detect any modifying effects of MICA alleles as an independently risk factor on the amyloidosis development. However, when we examined the effects of MICA alleles on the course of the disease and development of amyloidosis in the M694V homozygous patients, A5 allele had a protective effect against the development of amyloidosis (P = 0.038, OR(adj) 0.26 with A5 and P = 0.009, OR(adj) 4.42 without A5).

Conclusion: Though the effects of the MEFV genotypes seem clear, there are definitely other modifying factors or genes on the development of amyloidosis and on the course of the disease. For example, some MICA alleles have a protective effect on the prognostic factors in FMF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amyloidosis / etiology
  • Amyloidosis / genetics*
  • Cytoskeletal Proteins / genetics*
  • Familial Mediterranean Fever / complications
  • Familial Mediterranean Fever / genetics*
  • Female
  • Genotype
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Male
  • Point Mutation
  • Polymorphism, Genetic*
  • Pyrin
  • Trinucleotide Repeats*
  • Turkey


  • Cytoskeletal Proteins
  • Histocompatibility Antigens Class I
  • MEFV protein, human
  • MHC class I-related chain A
  • Pyrin