A functional promoter polymorphism in the macrophage migration inhibitory factor (MIF) gene associated with disease severity in rheumatoid arthritis
A functional promoter polymorphism in the macrophage migration inhibitory factor (MIF) gene associated with disease severity in rheumatoid arthritis
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DOI：
10.1038/sj.gene.6363867
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发表时间：
2002-05-01
影响因子：
5
通讯作者：
Bucala, R
中科院分区：
文献类型：
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作者：
Baugh, JA;Chitnis, S;Bucala, R
巨噬细胞移动抑制因子（MIF）是一种有效的促炎细胞因子，调节糖皮质激素的抗炎作用。MIF在细胞因子级联中的重要作用是与内源性糖皮质激素协同作用，以控制炎症反应的设定点和幅度。在类风湿性关节炎中，MIF在循环和滑膜关节中的表达升高。在实验动物模型中，MIF也与关节损伤和疾病病理学的发展有关。我们在此描述了一种新的CATT-四核苷酸重复多态性的位置-794人的MIF基因，并表明它在功能上影响的活性的MIF启动子在基因报告基因测定。我们描述了四种基因型，其中包括5，6，7，或8-CATT重复单位，并显示5-CATT等位基因具有最低水平的基础和刺激的MIF启动子活性在体外。在类风湿性关节炎患者队列中，低表达的5-CATT重复等位基因的存在与低疾病严重程度相关。
The macrophage migration inhibitory factor (MIF) is a potent pro-inflammatory cytokine and regulates the anti-inflammator effects of glucocorticoids. An important role for MIF within the cytokine cascade is to act in concert with endogenous glucocorticoids to control the set-point and magnitude of the inflammatory response. Elevated expression of MIF in the circulation and in the synovial joint has been documented in rheumatoid arthritis. MIF also has been linked to the development of joint damage and disease pathology in experimental animal models. We describe herein a novel CATT-tetranucleotide repeat polymorphism at position -794 of the human Mif gene and show that it functionally affects the activity of the MIF promoter in gene reporter assays. We describe four genotypes which comprise 5, 6, 7, or 8-CATT repeat units and show that the 5-CATT allele has the lowest level of basal and stimulated MIF promoter activity in vitro. The presence of the low expressing, 5-CATT repeat allele correlated with low disease severity in a cohort of rheumatoid arthritis patients.