Association of FMF-related (MEFV) point mutations with secondary and FMF amyloidosis.

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.
CONCLUSION: 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. Copyright 2004 S. Karger AG, Basel