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.