| Summary: | 碩士 === 高雄醫學大學 === 醫學研究所 === 98 === Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease characterized primarily by involvement of the axial skeleton including sacroiliac joint and spine. Behcet’s disease (BD) is a systemic disease based on vasculitis of small vessels. Both AS and BD belong to autoimmune diseases, but the etiology of this two diseases are unclear. It is believed to be due to an abnormal immune response triggered by environmental agents in a genetically predisposed individual. NF-κB is the most important regulator in the expression of the pro-inflammatory cytokine genes. If IκBα, the inhibitor of NF-κB, cannot retain NF-κB in cytoplasm, the diseases might be developed. Out of control on NF-κB will induce overexpressions of the immune associated genes. Promoter is the most important site to regulate the gene expression. In this study, we investigate the association of IκBα promoter polymorphisms with AS and BD, the IκBα −881 A/G, −826 C/T, −550 A/T, −519 C/T and −297 C/T polymorphisms were determined by the polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)method. Furthermore, Luciferase reporter assays were used to measure the activities of different haplotypes of IκBα promoter. This study demonstrated that IκBα -826T allele and CT, TT genotypes were associated with AS and BD in Taiwan. Especially, the -826TT genotype was associated with the development of skin lesion in BD. In addition, IκBα -881A -826T -550A -519C -297C, -881A -826C -550A -519T -297C and -881A -826T -550A -519C -297C, -881A -826T -550A -519T -297C haplotypes might be related to susceptibility to AS and BD, respectively. In contrast, -881A -826C -550A -519C -297C haplotype frequency was significantly lower in these two diseases. On the other hand, IκBα promoter activity in frequencies of haplotype of -826C -550A -519T and -826T -550A -519T were lower than that of the others. In conclusion, IκBα promoter polymorphisms are related to the sustability and clinical manifestation of AS and BD.
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