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Although the etiology of Behçet's Disease (BD; MIM 109650) remains to be clearly elucidated, levels of tumor necrosis factor alpha (TNF-alpha) have been reported to be significantly elevated in BD patients, and TNF-alpha blockers have been demonstrated to exhibit some degree of therapeutic efficacy for a certain subset of BD sufferers. In this study, we have conducted an analysis of the TNFA haplotypes in the promoter response element that affect the binding affinity of specific transcription factors, in order to characterize their association with the clinical features of BD. Six polymorphisms in the promoter region of TNFA were genotyped in 254 BD patients and 344 control subjects, via the PCR-RFLP technique. TNFA -1031*C, -863*A and -308*G alleles were associated with an increased risk of BD (p=0.030, OR=1.4; p=0.008, OR=1.5; p=0.010, OR=1.8, respectively). The sole TNFA haplotype -1031C-863A-857C-376G-308G-238G, was associated with a 1.6 fold increase in the risk of BD, whereas the TNFA haplotype -1031T-863C-857C-376G-308A-238G was associated with a 0.6 decreased risk of BD. The TNFA -1031*C, -863*A, -857*C and -308*G alleles were significantly associated with BD. The findings of this study, collectively, indicate that TNFA haplotypes in the promoter response elements may exert significant influence on susceptibility to BD.

Association ofTNFAPromoter Region Haplotype in Behçet's Disease