BEHCET'S DISEASE IS ASSOCIATED WITH MEFV GENE MUTATIONS

Background: Behcet's disease (BD) is a systemic inflammatory disorder of unknown etiology. BD has a strong genetic contribution in its pathogenesis, and HLA-B51 has been shown as the strongest genetic association described so far. Several non-HLA genes have been postulated in BD pathogenesis, including familial Mediterranean fever (FMF)-related MEFV gene. Both BD and FMF are prevalent in Eastern Mediterranean countries, and previous studies suggested an association between MEFV mutations and vascular involvement in BD. Objectives: In this study, we aimed to analyse the frequency and clinical significance of commonly observed MEFV mutations in a larger group of BD patients of Turkish origin. Methods: The study group consisted of 280 BD patients (164 male, 116 female) and 100 healthy controls. All patients fulfilled the International Study Group criteria for BD, and none of the patients described FMF-related symptoms. We isolated genomic DNA from all subjects, and genotyping for the MEFV gene M694V, V726A, M680I, E148Q mutations was done by polymerase chain reaction-restriction fragment length polymorphism. The study protocol was approved by local ethics committee, and all subjects provided written informed consent prior to blood collection. Results: The frequency of BD patients carrying MEFV mutations was found to be significantly higher (27%) compared to the frequency in healthy controls (10%) (P<0.001, OR = 3,35, %95 CI 1,7-6, 8). Distribution of individual mutations in the control group was as follows: heterozygous M694V %3, heterozygous M680I %1, heterozygous V726A %1, heterozygous E148Q 5%, complex alleles M694V/E148Q 1%, V726A/E148Q 1%. We identified 7.9% of BD patients as heterozygous for M694V, 12.9% of patients as heterozygous for E148Q and 0.4% of patients as homozygous for E148Q, 4.3% of patients as heterozygous for V726A, and 2,9% BD patients as heterozygous for M680I. We observed no association between the MEFV mutations and any of the BD manifestations, nor the disease severity. This study did not provide an evidence for increased risk of vascular involvement in BD patients who are positive for MEFV mutations. Conclusion: This study shows that frequency of FMF-related mutations is significantly increased in BD patients of Turkish origin. These findings suggest that MEFV-associated inflammatory pathways may contribute to the pathogenesis of BD in populations where FMF-related mutation carrier rate is high. However, no assocition has been observed between the manifestations/severity of BD and MEFV mutations, and our findings have not supported previous findings of a tendency for vascular involvement for mutation-positive patients. Disclosure of Interest: Nothing to declare relevant to this study.Citation: Annals of the Rheumatic Diseases, volume 68, supplement 3, year 2009, page 178Session: Genomics, genetic basis of disease and HLA/T cell recognition (Poster Presentations )