Predictors of AA amyloidosis in familial Mediterranean fever

• DOI: 10.1007/s00296-014-3205-x
• Publication Date: 2015-01-13T12:55:08Z
• Authors: Nikolay A. Mukhin; Lidiya V. Kozlovs...; Marina V. Bogdanova; Vilen V. Rameev; Sergey V. Moiseev; Armine Kh. Simonyan
• Keywords: Adult; Genetic Markers; Male; 0301 basic medicine; Heterozygote; Chi-Square Distribution; DNA Mutational Analysis; Homozygote; Amyloidosis; Armenia; Pyrin; Prognosis; Familial Mediterranean Fever; 3. Good health; Cytoskeletal Proteins; 03 medical and health sciences; Phenotype; Mutation; Odds Ratio; Humans; Female; Genetic Predisposition to Disease; Retrospective Studies

The aim of the study was to evaluate the clinical and genetic predictors of AA amyloidosis in patients with familial Mediterranean fever (FMF). We retrospectively studied 170 Armenian patients who were admitted to the two tertiary centers in 2003-2014. The diagnosis of amyloidosis that was suspected clinically (new proteinuria or nephrotic syndrome) was confirmed histologically. Screening for MEFV gene mutations was performed in 70 patients. The most common genotype was M694V/M694V (in 36 % of patients). Biopsy-proven AA amyloidosis was found in 102 (60 %) of 170 patients. AA amyloidosis was diagnosed in 17 (68 %) of 25 patients with homozygous M694V mutation, 17 (53 %) of 32 patients with heterozygous M694V allele and 4 (31 %) of 13 patients with other MEFV gene mutations. The M694V homozygosity and heterozygosity were associated with increased risk of AA amyloidosis, but this association did not reach statistical significance (odds ratio 2.43; 95 % CI 0.87-6.76, and 3.33; 0.91-12.1, respectively). Male gender, early onset of disease, severity of FMF, frequent attacks, peritonitis, pleuritis and erysipelas-like erythema also did not predict AA amyloidosis development. Recurrent arthritis was the only clinical finding that was significantly associated with AA amyloidosis (odds ratio 2.28; 95 % CI 1.17-4.42). Involvement of the joint synovial membrane, that is capable of active serum amyloid A production, is the main predictor of renal amyloidosis in FMF.