MEFV mutations in Beh�et's disease

Abstract

Familial Mediterranean fever (FMF) and Behçet's disease (BD), both inflammatory diseases, are highly prevalent in the Middle Eastern and Mediterranean populations. FMF is a Mendelian autosomic recessive disease linked to MEFV, a gene of unknown function. BD in contrast is a polyfactorial disease associated with the major histocompatibility complex. Because FMF and BD have epidemiological similarities, we asked whether the FMF gene was implicated in BD. We screened for the common MEFV mutations a cohort of 114 chromosomes from definite BD patients [meeting the criteria of the International study group] and probable cases [meeting at least two of these criteria]. We screened in parallel an ethnically matched cohort of FMF and control chromosomes. The M694V, V726A and E148Q mutations tended to be more frequent in definite BD (2.6%, 2.6%, and 5.2%, respectively) than in controls (0%, 0%, and 2.2%). The P706 polymorphism was found in 10.5% of the probable BD chromosomes, but in only 1.6% of the controls (p=0.01). Because some MEFV mutations were more frequent in BD than in controls, we suggest that they may act as additional susceptibility factors in BD. Hum Mutat 16:271–272, 2000. © 2000 Wiley‐Liss, Inc.

The significance of paired MEFV mutations in individuals without symptoms of familial Mediterranean fever

“…Carriers of MEFV mutations have been reported to be more susceptible to developing Behçet's disease, 15 and we had suggested that the presence of certain pyrin variants might increase the severity of inflammatory rheumatological diseases. 10 Genetic analyses of relatives of FMF patients or certain ethnic groups have disclosed up to 4% of individuals having two MEFV mutations but not expressing FMF ('phenotype III').…”

Familial Mediterranean Fever in the World

“…The possibility that the Silk Road was also the route for spreading FMF, as is the case with Behçet's disease (BD), is quite plausible. Supporting this view are the studies claiming that FMF is more prevalent among patients with BD than in the control populations, and that patients with BD carry MEFV mutations more than controls (26,27). However, such a possibility would predict a larger repertoire of mutations in Japan (similar to that found among Turkish and Armenian patients).…”

Targeted resequencing implicates the familial Mediterranean fever gene MEFV and the toll-like receptor 4 gene TLR4 in Behçet disease

“…Mutations in this gene are responsible for the recessive autoinflammatory disease familial Mediterranean fever (FMF), for which a high carrier rate has been found in Mediterranean populations, suggesting a selective advantage of the FMF-associated alleles (14). FMF-associated variants have previously been suggested to play a role in BD (15,16). A closer look at the MEFV variants showed that the significance was primarily derived from a single FMF mutation, p.Met694Val (M694V) (without M694V, C-alpha permuted P = 0.14), indicating that variants such as p.Met680Ile and p.Val726Ala, which are two other mutations commonly responsible for FMF in this population (14), do not confer strong risk for BD in the heterozygous state (Table 1 and Table S3).…”