Search

Familial Mediterranean fever (FMF) is an autosomal-recessive, inflammatory disorder characterised by short, recurrent attacks of fever, accompanied by pain in the abdomen, chest, or joints and complications of amyloidosis. Recently, we observed a significant association between the serum amyloid A1 (SAA1) β/β genotype and a delayed disease onset in 386 M694V homozygous FMF patients. This follow-up study was conducted to additionally analyse MEFV genotypes other than M694V/M694V for a possible influence of the SAA1 genotype on the age of disease onset.A total of 700 Armenian patients diagnosed with FMF based on the Tel-Hashomer criteria and carrying two MEFV mutant alleles were included in this study. Patients were divided into three MEFV genotypic subgroups: M694V homozygotes (M694V/M694V), M694V compound heterozygotes (M694V/Other), and patients with genotypes excluding M694V (Other/Other). MEFV and SAA1 analyses were performed by a commercial reverse-hybridisation assay, and resulting genotypes were matched against the demographic and clinical characteristics of the patients.Within the subgroup of M694/M694 homozygotes, SAA1 genotype β/β could be identified in 115 (34.43%) and 32 (61.54%) patients with an age of onset20 and ≥20 years, respectively(p0.001). However, no such relationship could be observed for MEFV genotypic subgroups M694V/Other (p=0.465) and Other/Other (p=0.697).Our data suggest, that the influence of SAA1 genotypic variation on the age of disease onset restricts to FMF patients homozygous for MEFV mutation M694V.

Familial Mediterranean fever (FMF) is a hereditary periodic disease characterised by recurrent attacks of fever and serositis. The most devastating complication of FMF is amyloidosis (AA) affecting mainly the kidneys. 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.Information about the MEFV mutations, SAA polymorphisms and FMF clinical features, were obtained for 1017 FMF patients, from the database of the Center of Medical Genetics in Yerevan. For identifying probable correlation between the MEFV and SAA genotype and clinical features of FMF, regression logistic analyses were conducted between the genotype and phenotype of the patients.Patients homozygous for M694V were highly associated with all the clinical features of FMF and its complications - proteinuria and amyloidosis. None of the SAA1 polymorphisms had any correlation with FMF clinical features. However, homozygosis for SAA1 α/α polymorphism was associated with proteinuria and amyloidosis whereas carrying the β/β polymorphism was found to be protective for amyloidosis.The SAA1 α allele is strongly associated with amyloidosis in FMF patients. This observation is valid in inflammatory diseases other than FMF too. SAA1 polymorphism has no effect on the clinical features of FMF. M694V homozygosis is highly associated withal typical features of FMF and with amyloidosis. FMF course in Armenia is similar to that in Middle Eastern countries where FMF disease is common.