T helper 1 type cytokines polymorphisms: association with susceptibility to Behçet’s disease

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.

Investigation of the association between Toll-like receptor 2 gene polymorphisms and Behçet's disease in Japanese patients

“…The main function of TLRs is the induction of inflammatory cytokines and effector molecules; TLR4 induces the production of several T-helper (Th)-1 and Th2 cytokines [17]. Several studies [37][38][39][40] demonstrated a significant increase of Th1 cytokines (e.g., IL-1, IL-2, IL-12, IL-17, IL-18, tumor necrosis factor-Â, and interferon-Ä in BD patients, suggesting that Th1 cytokines are predominant in BD, whereas a significant increase of some Th2 cytokines was also reported in BD patients [39,[41][42][43]. Therefore, TLR4-induced cytokines secretion in response to LPS and HSP may play an important role in the pathogenesis of BD.…”

Genetic susceptibility to Graves’ ophthalmopathy: the role of polymorphisms in proinflammatory cytokine genes

“…The lack of an association between the À330T/G polymorphism and rheumatoid arthritis and Behcet's disease has been reported before. 36,44 Our patients with GO were not significantly different from those without GO in allele and genotype frequencies of IL-6 at positions À174 and nt565. In line When comparing patients with and without GO.…”

“…The significantly increased frequencies of the UTR 5644T allele and AT and TT genotypes in our GO patients are in support of the hypothesis. This polymorphism is involved in pathogenesis of Behcet's disease 36 and lichen planus, 37 but to our knowledge this study is the first to suggest the involvement of this polymorphism in GO.…”

mRNA Expression Level of Interleukin Genes in the Determining Phases of Behçet's Disease

“…No significant difference was found in the genotype distribution or allele frequency of the IL1A -889(C/T) polymorphism between patients and controls in our study. Previous studies demonstrated that the presence of the IL1A -889C allele was significantly associated with BD10,11,12, although Coskun et al7 did not observe any such relationship.…”