A functional variant in FCRL3, encoding Fc receptor-like 3, is associated with rheumatoid arthritis and several autoimmunities
A functional variant in FCRL3, encoding Fc receptor-like 3, is associated with rheumatoid arthritis and several autoimmunities
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DOI：
10.1038/ng1540
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发表时间：
2005-05-01
期刊：
影响因子：
30.8
通讯作者：
Yamamoto, K
中科院分区：
文献类型：
--
作者：
Kochi, Y;Yamada, R;Yamamoto, K
类风湿性关节炎是一种常见的自身免疫性疾病，具有复杂的遗传病因。在这里，我们确定了一个SNP的FCRL 3，Fc受体样家族的成员，与类风湿性关节炎的易感性（比值比= 2.15，P = 0.0000085）的启动子区域。这种多态性改变核因子-κ B的结合亲和力并调节FCRL 3的表达。我们观察到FCRL 3在B细胞上的高表达，并在具有疾病易感基因型的个体中增加自身抗体的产生。我们还发现SNP与自身免疫性甲状腺疾病和系统性红斑狼疮的易感性之间存在关联。因此，FCRL 3可能在自身免疫中具有关键作用。
Rheumatoid arthritis is a common autoimmune disease with a complex genetic etiology. Here we identify a SNP in the promoter region of FCRL3, a member of the Fc receptor-like family, that is associated with susceptibility to rheumatoid arthritis ( odds ratio = 2.15, P = 0.00000085). This polymorphism alters the binding affinity of nuclear factor-kappa B and regulates FCRL3 expression. We observed high FCRL3 expression on B cells and augmented autoantibody production in individuals with the disease-susceptible genotype. We also found associations between the SNP and susceptibility to autoimmune thyroid disease and systemic lupus erythematosus. FCRL3 may therefore have a pivotal role in autoimmunity.