Journal
JOURNAL OF KOREAN MEDICAL SCIENCE
Volume 21, Issue 4, Pages 596-601Publisher
KOREAN ACAD MEDICAL SCIENCES
DOI: 10.3346/jkms.2006.21.4.596
Keywords
tumor necrosis factor-alpha; Behcet syndrome; haplotypes; polymorphisms; single nucleotide
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Although the etiology of Behcet'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 BID 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 BID. Six polymorphisms in the promoter region of TNFA were genotyped in 254 BID 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 BID (p=0.030, OR=1.4; p=0.008, OR=1.5; p=0.010, OR=1.8, respectively). The sole TNFA haplotype -1031C-863-A857C-376G-308G-238G, was associated with a 1.6 fold increase in the risk of BID, whereas the TNFA haplotype -1031 T-863C-857C-376G-308A-238G was associated with a 0.6 decreased risk of BID. The TNFA -1031*C, -863*A, -857*C and -308*G alleles were significantly associated with BID. The findings of this study, collectively, indicate that TNFA haplotypes in the promoter response elements may exert significant influence on susceptibility to BID.
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