Behçet's disease and hereditary periodic fever syndromes: casual association or causal relationship?
OBJECTIVE
Mutations in the MEFV and the type 1 TNF receptor (TNFRSF 1A) genes have recently been linked to familial Mediterranean fever (FMF) and TNF receptor-associated periodic syndrome (TRAPS), respectively. A higher prevalence of Behçet's disease (BD) among FMF patients has been described compared to the general population. The aim of this study was to evaluate whether FMF TRAPS and BD could be genetically related.


METHODS
We screened a cohort of 50 BD patients and 100 healthy subjects for the common MEFV and TNFRSF 1A mutations. An initial screening of exons 10 and 2 of the MEFV gene and exon 4 of the TNFRSF 1A was performed in all chromosomes.


RESULTS
The heterozygous MEFV mutation (K695R) was found in one (2%) BD patient. Analysis for FMF mutations in the control group revealed that 5 (5%) individuals bore MEFV gene mutations (3 were heterozygous for the E148Q and 2 were heterozygous for the A744S). At codon 202, there were no differences in allele frequencies between BD and control population: 73%R 27%Q in the BD patients vs 75%R 25%Q in controls. Concerning mutations in the TNFRSF 1A gene, the R92Q mutation was present in heterozygous state in one (2%) BD patient and in 4 (4%) controls without differences between allele frequencies: 99%R 1%Q in BD patients vs 98%R 2%Q in controls, respectively. There was no association between the clinical manifestations of BD patients and the presence of a particular polymorphism or a mutation.


CONCLUSIONS
Neither FMF nor TRAPS are genetically associated with BD in our cohort of Spanish patients.
Espinosa
G
G
Systemic Autoimmune Diseases Unit, Institut d 'Inves- tigacions Biomèdiques August Pi i Sunyer, Hospital Clinic, Barcelona, Catalonia, Spain. gespino@clinic.ub.es
Arostegui
J I
JI
Plaza
S
S
Rius
J
J
Cervera
R
R
Yagüe
J
J
Font
J
J
D001528:Behcet Syndrome / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D003598:Cytoskeletal Proteins / Q000235:genetics; D004252:DNA Mutational Analysis; D010505:Familial Mediterranean Fever / Q000235:genetics* / Q000473:pathology; D005260:Female; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D000071198:Pyrin; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D047888:Receptors, Tumor Necrosis Factor, Type I; D053319:Tumor Necrosis Factor Decoy Receptors
D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071198:Pyrin; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D053319:Tumor Necrosis Factor Decoy Receptors; C069521:recombinant human tumor necrosis factor-binding protein-1