Inhibitor IκBα Promoter Functional Polymorphisms in Patients with Rheumatoid Arthritis
Inhibitor IκBα Promoter Functional Polymorphisms in Patients with Rheumatoid Arthritis
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DOI：
10.1007/s10875-010-9439-9
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发表时间：
2010-09-01
影响因子：
9.1
通讯作者：
Yen, Jen-Hsien
中科院分区：
文献类型：
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作者：
Li, Ruei-Nian;Hung, Yu-Hung;Yen, Jen-Hsien
类风湿性关节炎（RA）是一种慢性炎症性疾病，除了关节外，还可能累及关节外器官。许多促炎细胞因子参与 RA 的炎症过程。 I kappa B α 与 NF-kappa B 结合，是调节炎症过程的关键角色。我们进行了实验来确定不同启动子多态性对 I kappa B α 启动子转录活性和 RA 发展的影响。构建了不同的 I kappa B α 启动子报告基因，并在人单核细胞 THP-1 细胞中进行了检查。从高雄医科大学医院招募了 140 名患者和 115 名健康对照。具有-826C、-550A、-519T 和-826T、-550A、-519T 基因型的 IκB α 启动子构建体的活性表达为其他构建体活性水平的一半。含有位点-550A/T和-519T的启动子构建体具有降低的类风湿性关节炎风险。 -826C/T基因型的比值比与引起类风湿性关节炎的风险增加显着相关，而-826T/T基因型仅与RA风险的轻微增加相关，但没有统计学意义（比值比=1.2；95%置信区间，0.4-3.8）。T等位基因的增加与RA发病风险和发病倾向的显着增加相关。 I kappa B α 启动子多态性与类风湿性关节炎疾病严重程度之间的关联部分归因于 I kappa B α 启动子的不同转录活性和 NF-kappa B 的激活。
Rheumatoid arthritis (RA) is a chronic inflammation disease that may involve extra-articular organs in addition to joints. Many proinflammatory cytokines are involved in the inflammatory process of RA. I kappa B alpha conjugates with NF-kappa B and is a key player in regulation of the inflammatory process. We carried out experiments to define the effect of different promoter polymorphisms on the transcriptional activities of I kappa B alpha promoter and the development of RA.Different I kappa B alpha promoter reporters were constructed and were examined in human mononuclear cells, THP-1 cells. One hundred forty patients and 115 healthy controls were recruited from the Kaohsiung Medical University Hospital.The activities of I kappa B alpha promoter constructs with -826C, -550A, -519T, and -826T, -550A, -519T genotypes were expressed at one half the activity level of other constructs. Promoter constructs containing the sites -550A/T and -519T had a reduced risk of rheumatoid arthritis. The odds ratio of -826C/T genotype was significantly associated with an increase of risk in causing rheumatoid arthritis, whereas -826T/T genotype was associated only with a slightly increased risk of RA, but without statistical significance (odds ratio = 1.2; 95% confidence interval, 0.4-3.8).The increase of T allele was associated with a significant increased risk and the tendency to the pathogenesis of RA. The association between I kappa B alpha promoter polymorphisms and disease severity of rheumatoid arthritis is partly due to different transcriptional activities of I kappa B alpha promoter and the activation of NF-kappa B.