title: Association of FMF-related (MEFV) point mutations with secondary and FMF amyloidosis.
abstract: BACKGROUND
  Familial Mediterranean fever (FMF) is the major cause of AA amyloidosis in Turkey. M694V mutation in MEFV gene was suggested to be associated with severe clinical features and amyloidosis of FMF.
  
  
  METHODS
  In this study, the frequencies of three FMF-related MEFV mutations (M694V, M680I and V726A) were investigated in FMF patients with (AA-FMF, n = 37) and without amyloidosis (non-AA-FMF, n = 35), in patients with secondary amyloidosis related to non-FMF inflammatory conditions (S-AA, n = 19) and in a non-inflammatory control group (n = 185) by molecular genetic studies using polymerase chain reaction with the ARMS (amplification refractory mutation system) method.
  
  
  RESULTS
  Both AA and non-AA-FMF patients had significantly higher MEFV mutations compared to non-inflammatory controls (81 and 62.7% respectively vs. 4.2%, p = 0.0001). AA-FMF patients carried significantly more MEFV mutations than non-AA-FMF patients (p = 0.01). M694V was the most common mutation in both FMF groups (63.5 vs. 51.4%), however allele frequency (p = 0.17) and the number of homozygous patients for this mutation did not differ between the groups (p = 0.77). Although lower compared to FMF patients, S-AA patients also had a significantly higher incidence of MEFV mutations than non-inflammatory controls (21 vs. 4.2%) (p = 0.0002). M694V was the only MEFV mutation in this group.
  
  
  CONCLUSIONS
  MEFV mutations are found to be increased both in FMF and non-FMF associated secondary amyloidosis in our study; however, no clear association between M694V and amyloidosis is observed, except in the non-FMF group. Our results suggest that MEVF mutations may also serve as a severity marker for other inflammatory conditions.
authors.affiliation: Department of Rheumatology, Marmara University School of Medicine, Istanbul, Turkey.
authors.forename: M Pamir
authors.initials: MP
authors.lastname: Atagunduz
authors.forename: Serhan
authors.initials: S
authors.lastname: Tuglular
authors.forename: Gulcin
authors.initials: G
authors.lastname: Kantarci
authors.forename: Emel
authors.initials: E
authors.lastname: Akoglu
authors.forename: Haner
authors.initials: H
authors.lastname: Direskeneli
mesh_terms: D000328:Adult; D000686:Amyloidosis / Q000209:etiology / Q000235:genetics*; D001168:Arthritis / Q000150:complications / Q000235:genetics; D003093:Colitis, Ulcerative / Q000150:complications / Q000235:genetics; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D010505:Familial Mediterranean Fever / Q000150:complications / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011506:Proteins / Q000235:genetics*; D000071198:Pyrin
chemical_list: D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D011506:Proteins; D000071198:Pyrin