We compared the haplotypes of FMF patients with and without amyloidosis in each ethnic group separately and identified 14 different MEFV core haplotypes.
The role of DNA analysis is discussed with respect to understanding the pathogenesis of the fever and assessing the risk of amyloidosis in specific mutations of the MEFV gene.
A significant association was found between amyloidosis and the most common mutation in exon 10 of the FMF gene (MEFV), M694V (for M694V homozygotes, relative risk = 1.77; 95% CI = 1.16-2.71).
We compared the frequencies of seven MEFV mutations (M694V, M680I, V726A, M694I, K695R, R761H, E148Q) and the clinical findings in 20 Turkish FMF patients who had not developed amyloidosis by the age of 40 years in the absence of colchicine therapy, with those in 27 Turkish amyloidosis patients.
In familial Mediterranean fever, the severity of the disease and the risk of renal amyloidosis are correlated with mutations in MEFV, and the serum amyloid-associated protein (SAA)1 alpha/alpha allele is a modifying factor for amyloidosis.
However, when FMF/amyloidosis patients (n:47) were taken as another group, the difference was significant (p= 0.01) indicating that the carriers of 138Gly are more prone to amyloidosis [odds ratio 3.1 (CI 95% 1.57-5.75)].
In phenotype II amyloidosis patients, the distribution of the four common MEFV mutations was not significantly different from that found in all FMF patients with typical symptoms who do or do not develop amyloidosis.
In phenotype II amyloidosis patients, the distribution of the four common MEFV mutations was not significantly different from that found in all FMF patients with typical symptoms who do or do not develop amyloidosis.
In this study, we analyzed the contribution of genotypes at the MEFV and SAA1 loci to disease severity and to the development of amyloidosis, and further defined the factors affecting the clinical profile of FMF.
The influence of FMF gene (MEFV) mutations and/or unknown environmental factors and other genetic modifiers are likely to affect the phenotypic variations of the disease and the development of amyloidosis.
Male sex coupled with articular manifestations cause a 4-fold increase in susceptibility to amyloidosis in patients with familial Mediterranean fever homozygous for the M694V-MEFV mutation.
Fourteen MEFV mutations were screened and the SAA1 and MICA polymorphisms tested in 30 FMF patients with amyloidosis and 40 FMF patients without amyloidosis.
The E148Q variant of MEFV was present in two of the three patients with TNF receptor-associated periodic syndrome (TRAPS) complicated by amyloid in two separate multiplex TRAPS families containing 5 and 16 affected members respectively, and the single patient with Muckle-Wells syndrome who had amyloidosis was homozygous for this variant.
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.
The aim of this study was to examine the controversial issue of amyloidosis susceptibility in FMF by determining the relative contributions of MEFV and numerous epidemiologic factors to the risk of renal amyloidosis.
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.
The aim of this study was to examine the controversial issue of amyloidosis susceptibility in FMF by determining the relative contributions of MEFV and numerous epidemiologic factors to the risk of renal amyloidosis.