Altered Distribution of Polymorphisms in the Promoter Gene for IL-10 in Patients with Behcet's Disease but not Those with Idiopathic Retinal Vasculitis

Abstract

Abstract: : Purpose: Polymorphisms in the upstream region of the anti-inflammatory cytokine IL-10 have been associated with alterations in its transcriptional activity. We studied the prevalence of 3 IL-10 promoter region polymorphisms in patients with Behcet’s disease and idiopathic retinal vasculitis. Methods: DNA was prepared from 74 patients with Behcet’s disease, 160 patients with retinal vasculitis and 100 controls. Polymorphisms in the IL-10 gene region at positions –592, -819 and -1082 were detected by a multiplex SSP-PCR assay. Associations with disease were calculated by both allelic frequency and haplotype analysis. Results: Haplotype and allelic analysis revealed no significant differences in patients with retinal vasculitis compared to controls. Comparisons of the allelic frequencies showed a higher prevalence of the –1082 A allele and a lower prevalence of the –1082 G allele in patients with Behcet’s disease (p_c=0.007; OR for A=2.09, 95%CI 1.37-3.21. OR for G =0.59, 95%CI 0.38-0.93). In patients with Behcet’s disease there was a higher prevalence of the ATA compared to the ACC and GCC haplotypes (p_c<0.008; OR=2.79, 95% CI 1.72-4.52). This was particularly true in patients with two copy haplotypes (p_c=0.024; OR=5.14 95%CI 1.67-15.62). Conversely, the GCC haplotype was under-represented in patients (p_c=0.032;OR=0.38, 95%CI 0.20-0.75) No patients with ocular involvement had the two copy GCC haplotype (p_c<0.001; OR=0.0016 95%CI 0.0009-0.291) Conclusion: We describe an abnormal distribution of polymorphism in haplotypes of the IL-10 promoter region in patients with Behcet’s disease, especially those with eye involvement. This altered distribution may partly explain the immunological dysfunction observed in this disease.

Keywords: genetics • immunomodulation/immunoregulation • uveitis-clinical/animal model