Common MEFV mutations among Jewish ethnic groups in Israel: High frequencyof carrier and phenotype III states and absence of a perceptible biological advantage for the carrier state

Familial Mediterranean fever (FMF) is an autosomal recessive disease, chara cterized by recurrent attacks of fever and inflammation of serosal membrane s and gradual development of nephropathic amyloidosis. The recent cloning o f the FMF gene (MEFV) and identification of disease-associated mutations in most patients made the direct determination of FMF carrier frequency feasi ble. The aim of the present study was to investigate the carrier rate of th e most common MEFV mutations among different Jewish ethnic groups in Israel . Further, an attempt was made to elucidate the possible biological advanta ge that the heterozygote state may confer. Three hundred Ashkenazi, 101 Ira qi, and 120 Moroccan Jews were screened for the E148Q, V726A, and M694V mut ations (at least two most common mutations per group), with a resulting ove rall carrier frequency in the respective ethnic group of 14%, 29%, and 21%. No difference in morbidity between Ashkenazi carriers and non-carriers of MEFV mutations was discerned, although an excess of febrile episodes in car riers of the V726A and in carriers of either V726A or E148Q was evident (P < 0.02 and P < 0.05, respectively). The frequency of subjects with two MEFV mutations but not expressing FMF (phenotype III) was 1:300 in Ashkenazi Je ws and 1:25 in Iraqi Jews, exceeding the reported rate of overt FMF in thes e ethnic groups by 40-240 fold. These results affirm the high carrier rate among the studied Jewish ethnic groups in Israel and suggest that most subj ects with FMF mutations are unaffected. (C) 2001 Wiley-Liss, Inc.