Familial Mediterranean fever: Effects of genotype and ethnicity on inflammatory attacks and amyloidosis

Objective. The gene causing familial Mediterranean fever (FMF)-an autosomal recessive disease characterized by recurrent short episodes of fever assoc iated most commonly with peritonitis, pleuritis, and arthritis-has recently been found and several mutations identified. The most severe complication of the disease is amyloidosis, which can lead to renal failure. The aim of this study was to investigate the role of genetic versus nongenetic factors on the phenotype as well as on the development of amyloidosis in FMF in a large and heterogeneous group of patients. Methodology. We studied 382 patients from 4 ethnic origins living in differ ent environments: North African Jews, other Jews, Turks, Armenians living i n the United States, and Armenians from Yerevan, Armenia. Information regar ding amyloidosis was available for 371 patients. We examined the associatio n between the mutation M694V and the development of amyloidosis, and we als o compared the clinical characteristics of the inflammatory attacks in pati ents from different ethnic origins, while controlling for the type of mutat ion. Results. A significant association was found between amyloidosis and the mo st common mutation in exon 10 of the FMF gene (MEFV), M694V (for M694V homo zygotes, relative risk = 1.77; 95% CI = 1.16-2.71). Amyloidosis was present in 44 of 171 homozygous FMF patients (25.7%), in 22 of 143 compound hetero zygous FMF patients (15.4%), and in 7 of 57 patients carrying other mutatio ns (12.3%). In homozygotes for M694V who had not been treated with colchici ne before 20 years of age, the risk of amyloidosis developing before this a ge was 61.0%. In our series, there were no cases of amyloidosis in 16 patie nts carrying the common mutation E148Q. We found that the type and severity of the FMF inflammatory symptoms were associated with both the genotype an d the country of residence of the patient. Conclusions. In the light of the high frequency of amyloidosis in homozygot es for the mutation M694V, colchicine treatment should be given to this gro up irrespective of the severity of the inflammatory attacks to prevent the development of amyloidosis. Our findings also suggest that factors other th an genotype, such as environment or genes other than MEFV, play a role in t he determination of the severity of the inflammatory attacks in FMF.