T helper 1 type cytokines polymorphisms: association with susceptibility to Behcet's disease

Department of Physical Medicine and Rehabilitation, Medical Faculty, Ondokuz Mayis University, Samsun, Turkey.
Clinical Rheumatology (Impact Factor: 1.77). 08/2007; 26(8):1299-305. DOI: 10.1007/s10067-006-0503-z
Source: PubMed

ABSTRACT The pathogenesis of Behçet's disease (BD) is not fully understood and immunological abnormalities and genetic factors have been investigated. Because serum concentrations of mainly T helper 1 (Th1) type cells have been reported to be increased in BD, we aimed to investigate whether certain cytokine polymorphisms might represent a risk factor for developing BD. We genotyped 80 patients with BD and 105 healthy controls for interleukin (IL)-1 alpha (T/C -889), IL-1 beta (C/T -511, T/C +3962), IL-1R (C/T pst11970), IL-1RA (T/C mspa111100), IL-2 (T/G -330), IL-12 (C/A -1188), interferon (IFN)-gamma (A/T UTR 5644), and TNF-alpha (G/A -238) polymorphisms. Analyses of cytokine polymorphisms were performed with PCR-SSP. The genotype and allele frequencies of the patients and controls were compared and the association between the polymorphisms of the cytokines with the clinical findings was investigated. Genotype distribution showed significant differences between the patients and the controls for the IL-1 alpha -889, IL-1 beta -511, IL-1 beta +3962, IL-1R, IL-12, IFN- gamma, and TNF-alpha cytokines. We didn't observe significant difference in genotypic frequencies of IL-1RA and IL-2 in our study. Comparison of the IL-1 alpha -889, IL 1 beta -511, and IL 1 beta +3962 genotype frequencies showed significant increase in CC genotype between the patients and the controls. The individuals with IL-1R TT polymorphism had a higher risk for BD compared to patients with CT/CC polymorphism. Comparison of IL-12, IFN- gamma, and TNF-alpha, genotype frequencies showed significant increase in CA, AA, and AA genotypes between the patients and controls, respectively. The frequencies of genotypes according to the clinical features of the patients with BD did not show a significant difference (p>0.05). Our study suggests that development of BD might be determined by various cytokine gene polymorphisms. However, further studies on larger numbers of cases are needed before definite conclusions can be drawn.

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    ABSTRACT: Behçet's disease (BD) is a chronic inflammatory disease. Increased productions of cytokines including interleukin (IL)-1β and IL-18 are documented, and IL-1α and β gene polymorphisms are associated with susceptibility to the disease. IL-33 is a recently discovered member of IL-1 cytokine family. The aim of the study was to detect serum IL-33 level and IL-33 gene polymorphisms in a cohort of BD. Unrelated 117 patients with BD and 149 healthy controls (HC) were enrolled. Serum IL-33 levels were analyzed by enzyme-linked immunosorbent assay method. DNA samples were harvested using an appropriate commercial DNA isolation kit. Four single nucleotide polymorphisms of IL-33 gene (rs7044343, rs1157505, rs11792633 and rs1929992) were genotyped using the appropriate commercial primer/probe sets on real-time PCR. Serum IL-33 level was not significantly different in the BD and HC groups (p > 0.05). However, its level was lower in the active BD patients compared to the inactive ones and HC group (p = 0.044 and p = 0.037, respectively). There was no significant difference in terms of the genotypic and allelic distributions of rs1157505 and rs1929992 polymorphisms (p > 0.05 for all). However, the TT variants of rs7044343 and rs11792633 polymorphisms were very rare, and the T allele frequencies of these polymorphisms were lower, in the BD group compared to the HC group (p < 0.0001 for all). The rs7044343 and rs11792633 variants of IL-33 gene are associated with the decreased risk of BD in our cohort. Therefore, it may be concluded that IL-33 acts a protective role on the pathogenesis of BD.
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    ABSTRACT: Objectives. Polymorphisms in the Interleukin (IL)-1-related genes at the locations -889, -511, + 3962 and mspa1l 1100 have been investigated for possible association with Behçet's disease (BD). Methods. A literature-based search was conducted to identify all relevant studies. Five independent studies from Turkish population met the included criteria. Results. IL-1α -889 CT [odds ratio (OR) = 0.72, 95% confidence interval (CI) = 0.55-0.95], IL-1α -889 TT (OR = 0.61, 95% CI = 0.40-0.93), IL-1β + 3962 C (OR = 1.41, 95% CI = 1.07-1.88), IL-1β + 3962 T (OR = 0.71, 95% CI = 0.53-0.94) IL-1β + 3962 CC (OR = 2.08, 95% CI = 1.08-3.99), IL-1β + 3962 CT (OR = 0.58, 95% CI = 0.38-0.88), IL-1 receptor antagonist (IL-1 Ra) mspa1l 1100 CT (OR = 0.69, 95% CI = 0.49-0.96), IL-1 Ra mspa1l 1100 TT (OR = 1.50, 95% CI = 1.08-2.08) had a significant association with BD. The pooled estimates for IL-1α -889 C, IL-1α -889 CC, IL-1α -889 T had a non-significant association with BD. Conclusions. IL-1α -889 CT, IL-1α -889 TT, IL-1β + 3962 C, IL-1β + 3962 T, IL-1β + 3962 CC, IL-1β + 3962 CT, IL-1 Ra mspa1l 1100 CT, IL-1Ra mspa1l 1100 TT promoter polymorphisms may confer susceptibility to BD in Turkish population.
    Modern Rheumatology 11/2013; DOI:10.3109/14397595.2013.844304 · 2.21 Impact Factor
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    ABSTRACT: PurposeTo investigate the associations of single nucleotide polymorphisms (SNPs) of three genes (IL-12B, IL-12Rβ1 and IL-12Rβ2) in Behcet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Chinese Han population.MethodsA total of 806 BD cases, 820 VKH patients, and 1600 healthy controls were involved in this study. The first investigation included 400 BD patients, 400 VKH cases, and 600 healthy individuals. A second confirmatory study included a separate set of 406 BD patients, 420 VKH cases and another 1000 normal controls. Genotyping was carried out by PCR-restriction fragment length polymorphism assay and results were validated by using direct sequencing. The χ2 test was performed to compare the allele and genotype frequencies between cases and healthy controls.ResultsThis study comprised two phases. In the first phase study, a significantly increased frequency of the rs3212227/IL-12B genotype CC and C allele was found in BD patients as compared to controls (Bonferroni corrected p value (pc) = 0.009, OR 1.8; pc = 0.024, OR 1.3, respectively). Moreover, the frequency of the C allele of rs3212227/IL-12B was also significantly increased in VKH patients (pc = 0.012, OR 1.3, 95% CI 1.1 to 1.6). No associations were found for the other seven tested SNPs either in BD or VKH disease. The second study as well as the combined data confirmed the significant association of rs3212227/IL-12B with BD (CC genotype: combined pc = 6.3×10−7, OR = 1.8; C allele: combined pc = 2.0×10−5, OR = 1.3, respectively) and the C allele frequency of rs3212227/IL-12B as the risk factor to VKH patients (combined pc = 2.5×10−5, OR 1.3, 95% CI 1.2 to 1.5).ConclusionsOur study revealed that the IL-12B gene is involved both in the susceptibility to BD as well as VKH syndrome.
    PLoS ONE 05/2014; 9(5):e98373. DOI:10.1371/journal.pone.0098373 · 3.53 Impact Factor