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Ankylosing spondylitis (AS) is a highly heritable immune-mediated arthritis common in Turkish and Iranian populations. Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disease most common in people of Mediterranean origin. MEFV, an FMF-associated gene, is also a candidate gene for AS. We aimed to identify AS susceptibility loci and also examine the association between MEFV and AS in Turkish and Iranian cohorts. We performed genome-wide association studies in 1001 Turkish AS patients and 1011 Turkish controls, and 479 Iranian AS patients and 830 Iranian controls. Serum IL-1β, IL-17 and IL-23 cytokine levels were quantified in Turkish samples. An association of major effect was observed with a novel rare coding variant in MEFV in the Turkish cohort (rs61752717, M694V, OR = 5.3, P = 7.63×10−12), Iranian cohort (OR = 2.9, P = 0.042), and combined dataset (OR = 5.1, P = 1.65×10−13). 99.6% of Turkish AS cases, and 96% of those carrying MEFV rs61752717 variants, did not have FMF. In Turkish subjects, the association of rs61752717 was particularly strong in HLA-B27-negative cases (OR = 7.8, P = 8.93×10−15), but also positive in HLA-B27-positive cases (OR = 4.3, P = 7.69×10−8). Serum IL-1β, IL-17 and IL-23 levels were higher in AS cases than controls. Among AS cases, serum IL-1β and IL-23 levels were increased in MEFV 694V carriers compared with non-carriers. Our data suggest that FMF and AS have overlapping aetiopathogenic mechanisms. Functionally important MEFV mutations, such as M694V, lead to dysregulated inflammasome function and excessive IL-1β function. As IL-1 inhibition is effective in FMF, AS cases carrying FMF-associated MEFV variants may benefit from such therapy. [ABSTRACT FROM AUTHOR]

Recurrent aphthous stomatitis (RAS) is a common oral inflammatory disease with unknown etiology in which the immune system seems to have a role in oral tolerance. Interleukin (IL)-10 is a cytokine synthesis inhibitory factor. Single nucleotide polymorphisms (SNPs) of IL10 gene could alter this cytokine production. The aim of this study was to investigate frequencies of IL10 alleles and genotypes in a group of individuals with RAS. Genomic DNA of 60 Iranian patients with RAS were typed for IL10 gene (C/A −1082, C/T −819, and C/A −592), using PCR-SSP method. Frequency of each allele and genotype was compared to control group. A significantly higher frequencies of the T allele at position −819 ( p = 0.006) and the A allele at position of −592 ( p < 0.001) were found in the patients with RAS group, when compared to the controls. IL10 GA genotype at position −1082 ( p = 0.007), CA genotype at position −592 ( p = 0.001), and CT genotype at position −819 ( p = 0.001) were significantly higher in the RAS patients. The results of this study suggest that certain SNPs of IL10 gene have association with predisposition of individuals to RAS. However, further multicenter studies should be conducted to confirm the results of this study. [ABSTRACT FROM AUTHOR]

Background: Inflammatory cytokines have been known to be associated with Chronic Heart Failure (CHF). Given the importance of cytokines in the context of the failing heart, the prevalence of Interleukin-2 (IL-2) and Interferon-gamma (IFN-γ) polymorphisms was studied in patients with CHF due to ischemic heart disease in a case-control study. Methods: Fifty-six Iranian patients with CHF were enrolled in this study as the case group and compared with 139 healthy subjects, using polymerase chain reaction with sequence-specific primers method, so as to determine the frequency of alleles, genotypes and haplotypes of IFN-γ (+874 A/T) and IL-2 (-330 G/T, +166 G/T) SNPs. Results: The GG genotype at IL-2 -330 in patients with CHF was significantly over-represented in comparison with the control group (p=0.013). Such a positive genotypic association was also observed for IL-2 +166/TT (p=0.022). Meanwhile, the GT genotype frequency at IL-2 -330/GT in the patient group was significantly lower than the one in healthy controls (p=0.049). No significant association was detected between the IFN-γ gene polymorphisms and individuals' susceptibility to CHF. Conclusion: Certain genotypes in IL-2 gene were overrepresented in patients with CHF, which could render individuals more vulnerable to this disease. [ABSTRACT FROM AUTHOR]

Background: Proinflammatory cytokines have been known to be elevated in patients with Chronic Heart Failure (CHF). Given the importance of proinflammatory cytokines in the context of the failing heart, the prevalence of Tumor Necrosis Factor-α (TNF-α), Interleukin (IL)-6 polymorphisms in patients with CHF was studied due to ischemic heart disease. Methods: Forty three patients with ischemic heart failure were enrolled in this study and compared with 140 healthy individuals. The allele and genotype frequency of four Single Nucleotide Polymorphisms (SNPs) within the IL-6 (-174, nt565) and TNF-α (-308, -238) genes were determined, using Polymerase Chain Reaction with Sequence-Specific Primers (PCR-SSP) assay. Results: The frequency of the TNF-α (-238) A/A genotype was significantly higher in patients comparing to controls (p=0.043), while TNF-α G/A genotype at the same position decreased significantly, in comparison with controls (p=0.018). The most frequent haplotype for TNF-α was A/A in the patient group in comparison with controls (p=0.003). There was no significant difference in allele and genotype frequencies of IL-6 at positions -174 and nt565, and TNF-α at position -308. Conclusion: Certain alleles, genotypes, and haplotypes in TNF-α, but not IL-6, gene were overrepresented in patients with ischemic heart failure, which may, in turn, predispose individuals to this disease. [ABSTRACT FROM AUTHOR]