Objective. The pathogenesis of ankylosing spondylitis (AS) has a strong genetic contribution. Familial Mediterranean fever (FMF) is an autosomal recessively inherited autoinflammatory disorder caused by MEFV gene missense variations, and a clinical association between FMF and AS has been reported previously. The aim of this study was to analyze the association of common MEFV variations (M694V, M680I, V726A, and E148Q) with AS in a group of Turkish patients.Methods. The study group comprised 193 patients with AS and 103 matched healthy control subjects. All individuals were genotyped for 4 MEFV variations and HLA-B27 using genomic DNA, and association of the variations with the clinical and laboratory features of the patients was analyzed.Results. The MEFV missense variations were significantly more frequent in patients with AS (22.3%) compared with healthy control subjects (9.7%; odds ratio [OR] 2.67, 95% confidence interval [95% CI] 1.28-5.56). This difference was more prominent for exon 10 variations (M694V, V726A, M680I) (OR 3.75, 95% CI 1.41-9.97), especially for the most-penetrant variation M694V (OR 4.73, 95% CI 1.39-16.12). MEFV variations were more frequent in HLA-B27-negative patients with AS, and the difference was statistically significant in patients carrying exon 10 variants.Conclusion. FMF-related MEFV variations are associated with AS, and these variations may contribute to the pathogenesis of AS, especially in populations in which the prevalence of FMF is high.

Objective. Familial Mediterranean fever (FMF) is associated with more than 70 missense mutations in the MEFV gene. The purpose of this study was to investigate the relative expression of messenger RNA (mRNA) for the MEFV gene in peripheral blood leukocytes (PBLs) obtained from patients with FMF during attacks of acute abdominal inflammation as well as during asymptomatic periods.Methods. We studied 16 patients with FMF during an attack of acute peritonitis and 17 otherwise healthy individuals who were undergoing surgery because of acute appendicitis. Blood samples were collected from both groups of patients during both acute inflammatory and asymptomatic periods. Relative levels of MEFV mRNA in PBLs were detected with real-time reverse transcriptase-polymerase chain reaction using LightCycler, with 2 sets of primers for the MEFV gene (exons 7-10 and exons 2-3) and with primers for CIAS1 and PSTPIP1 genes. Expression levels were compared with ␤ 2 -microglobulin as an internal control.Results. MEFV expression was reduced in FMF patients during asymptomatic periods as compared with the non-FMF controls (P < 0.001). We observed a further decrease in MEFV expression in FMF patients during periods of inflammation (P ‫؍‬ 0.01). Reduced levels of MEFV mRNA were also noted during the preoperative period as compared with asymptomatic periods in control patients with acute appendicitis (P ‫؍‬ 0.01). CIAS1 expression in PBLs from patients with FMF was also found to be lower than that in the control patients. However, CIAS1 expression did not change with acute inflammation.Conclusion. This study confirmed that reduced expression of the MEFV gene is associated with inflammation and that it may be one of the pathogenic mechanisms of the attacks of inflammation in FMF patients, along with disease-associated variations in pyrin.

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Behçet's disease (BD) is a multisystem inflammatory disorder of unknown etiology, and infections with different microorganisms including streptococci have been claimed as triggers of inflammatory attacks in BD pathogenesis. Toll-like receptor 2 (TLR2) has been known to recognize several microbial antigens including that of streptococci, and TLR2 gene Arg753Gln polymorphism has been reported to be strongly associated with acute rheumatic fever with an odds ratio of 100. This study aimed to investigate the TLR2 gene Arg753Gln polymorphism in a group of patients with BD and rheumatic heart disease (RHD) and to analyze the role of genotyping errors resulting from duplicated gene segments. The study group consisted of 211 patients with BD, 95 patients with RHD, and 94 matched Turkish healthy controls. Because of the duplicated exon 3 in 23-kb upstream of the TLR2 gene, genotyping for the Arg753Gln polymorphism with polymerase chain reaction-restriction fragment length polymorphism method was carried out using a new set of primers and PstI restriction enzyme. TLR2 gene Gln753 allele was observed in two of 211 (1.0%) patients with BD, five of 95 (5.3%) patients with RHD, and two of 94 (2.1%) healthy controls. All patients and controls were found to be heterozygous for Arg753Gln polymorphism, except one patient with BD, who was homozygous for Gln753. Although a slight increase of heterozygosity was noted in patients with RHD, no statistically significant difference was observed in the distribution of Arg753Gln polymorphism in BD and RHD compared to healthy controls. In conclusion, TLR2 gene Arg753Gln polymorphism is not associated with BD nor with RHD; and a duplicated region of the TLR2 exon 3 located 23-kb upstream of the polymorphic region may explain contradictory association findings described so far.

OBJECTIVE: The aim of this study was to investigate the frequency of familial Mediterranean fever (FMF)-associated MEFV gene variations in patients with systemic lupus erythematosus (SLE). METHODS: The study group comprised 190 SLE patients and 101 healthy controls of Turkish origin with no clinical features of FMF. All individuals were genotyped for the four most common MEFV gene variations (M694V, M680I, V726A and E148Q) by PCR-restriction fragment length polymorphism analysis. RESULTS: The frequency of carrying any of the four MEFV gene variations under study was 15 % in patients with SLE and 10 % in the healthy controls (p = 0.23). After the exclusion of the less penetrant E148Q variation, re-analysis for the three penetrant mutations revealed a significant association between exon 10 variations and pericarditis [p = 0.038, odds ratio (OR) 3.5, 95 % confidence interval (CI) 1.0-12.1], and pleural effusion (p = 0.043, OR 5.2, 95 % CI 0.8-30.9). No significant association was detected between the MEFV gene variations and a higher acute phase response. CONCLUSIONS: The MEFV gene variations analyzed in our study do not seem to increase the overall susceptibility to SLE and do not have any strong association with its clinical manifestations. The possibility of a modest effect of penetrant exon 10 MEFV variants on the development of serosal effusions needs to be explored in a larger series of patients.