Amyloidosis in familial Mediterranean fever is associated with a specific ancestral haplotype in the MEFV locus

Familial Mediterranean fever (FMF) is a recessive disease characterized by recurrent attacks of inflammation of serosal membranes, and the gene respon sible, MEFV, has been recently identified. Amyloidosis is considered to be the most severe complication. Since colchicine is effective in preventing F MF amyloidosis and since this process can develop even prior to the FMF sym ptoms, lifelong colchicine treatment is recommended for all FMF patients. I dentification of the factor which determines amyloidosis will allow treatme nt to be directed only to those at risk. In order to investigate the associ ation between amyloidosis and MEFV haplotypes, we studied 56 families from three ethnic groups. We compared the haplotypes of FMF patients with and wi thout amyloidosis in each ethnic group separately and identified 14 differe nt MEFV core haplotypes. A significant association (P < 0.004) was found be tween amyloidosis and a specific core haplotype, 153bp:104bp at markers D16 S3370 and D16S2617, respectively. Amyloidosis was present in 20 out of 70 h omozygotes for this haplotype and in 6 out of 35 compound heterozygotes for this and other core haplotypes. None of the patients who did not carry thi s allele had amyloidosis. There was no association between the various hapl otypes and severity of the FMF symptoms, age of onset, or age at commenceme nt of colchicine. Further investigation of the MEFV haplotypes in additiona l patients is recommended as such an association may save many mildly affec ted or asymptomatic patients with non-amyloidotic genotypes from receiving unnecessary lifelong colchicine treatment. (C) 1998 Academic Press.