Common FMF alleles may predispose to development of Behcet's disease with increased risk for venous thrombosis.
BACKGROUND
Behcet's disease (BD) is an inflammatory disorder of unknown cause, associated with vasculitis. Arterial or venous thrombosis occurs in about 25% of BD patients. Familial Mediterranean fever (FMF) is another inflammatory disorder, which stems from mutations in the FMF gene (MEFV) and shares a number of features with BD.


OBJECTIVE
MEFV analysis in patients with BD suggests that mutated MEFV may act as a susceptibility gene in BD. We studied the rate and the clinical correlates of MEFV mutations in Israeli BD patients.


METHODS
Included were 54 BD patients who satisfied the International Study Group criteria for BD. All BD patients were genotyped using polymerase chain reaction (PCR) and restriction enzyme analysis for the three most common MEFV mutations (M694V, V726A, and E148Q). The association between BD manifestations and MEFV alleles was analysed.


RESULTS
Twenty-one BD patients were found to carry a single MEFV mutation and three additional patients were compound heterozygotes, a frequency significantly higher than that expected for ethnically matched healthy individuals. There were no statistically significant differences between carriers and non-carriers with respect to gender, frequency of HLA B5 antigen, cutaneous lesions, joint disease, and severity score. However, carriers did experience thrombosis more often [54% vs. 17%, p<0.005, odds ratio (OR) = 6.9, 95% confidence interval (CI) 1.75-26.9] and uveitis less often (20% vs. 40%, p<0.05, OR = 0.2, 95% CI 0.04-0.92).


CONCLUSIONS
MEFV appears to be a susceptibility and modifier gene in BD.
Rabinovich
E
E
Heller Institute of Medical Research, Sheba Medical Center, Tel Hashomer 52621, Israel.
Shinar
Y
Y
Leiba
M
M
Ehrenfeld
M
M
Langevitz
P
P
Livneh
A
A
D000328:Adult; D000483:Alleles; D001528:Behcet Syndrome / Q000150:complications / Q000208:ethnology / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007557:Israel; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000071198:Pyrin; D012307:Risk Factors; D020246:Venous Thrombosis / Q000235:genetics*
D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071198:Pyrin