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 current results indicate the germ-line mutations in both genetic biomarkers (MEFV and SAA1 genes) that are related to inflammation and amyloidosis processes may play a crucial role in CRF pathogenesis due to the long-term chronic inflammation.
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.
We compared the haplotypes of FMF patients with and without amyloidosis in each ethnic group separately and identified 14 different MEFV core haplotypes.
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.
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.
The M694V/M694V genotype was more common in patients with amyloidosis (37%) compared to patients without amyloidosis (18%) (p = 0.009).The frequency of MEFV carriers was 27%.
Aim of the study is to search for correlations between the MEFV genotype and the SAA polymorphisms with the clinical manifestations of FMF and the occurrence of amyloidosis in a large cohort of Armenian patients.
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.
However, our data suggest that the MEFV gene mutations may not be a genetic factor affecting the susceptibility of RA or the development of amyloidosis in a Japanese population.
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.
The chronic accumulation of inflammatory mediator in neuronal cells facilitates interactions of TXNIP-nucleotide binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) and NLRP3-ASC, which increases β-amyloid (Aβ) secretion.
So that we aimed in this study to investigate whether FMF patients with/without amyloidosis and with M694V homozygote mutation, have increased risk for atherosclerotic cardiovascular complications and to determine the strength of association between MEFV gene-mutation types.
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.
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.
Furthermore, the MEFV gene-mediated inflammatory pathway increased serum acute phase reactants, and the changes in the R202Q and M694V could play a role in inflammatory-genetic diseases, such as FMF, FMF-associated amyloidosis and chronic periodontitis.