Functional SNPs in CD244 increase the risk of rheumatoid arthritis in a Japanese population
Functional SNPs in CD244 increase the risk of rheumatoid arthritis in a Japanese population
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DOI：
10.1038/ng.205
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发表时间：
2008-10-01
期刊：
影响因子：
30.8
通讯作者：
Yamamoto, Kazuhiko
中科院分区：
文献类型：
--
作者：
Suzuki, Akari;Yamada, Ryo;Yamamoto, Kazuhiko
类风湿性关节炎是一种慢性自身免疫性炎症性疾病，具有复杂的遗传病因。信号淋巴细胞激活分子 (SLAM) 家族的成员在先天免疫和常规淋巴细胞中发挥着关键作用。我们在包含多个 SLAM 家族基因的染色体 1q 区域中发现了与类风湿性关节炎相关的连锁不平衡区块。在此区块中，该关联在来自日本的两个独立类风湿性关节炎队列中的 CD244 中的两个功能性 SNP（rs3766379 和 rs6682654）处达到峰值（P = 3.23 x 10(-8) 和 P = 7.45 x 10(-8)）。我们还发现了一个患有系统性红斑狼疮的日本队列，其基因型分布与类风湿性关节炎队列相似。我们证明，类风湿关节炎易感等位基因 rs3766379 和 rs6682654 及其单倍型在荧光素酶和等位基因特异性转录本定量测定中增加了表达。 CD244 是类风湿关节炎的遗传危险因素，可能在类风湿关节炎和系统性红斑狼疮共有的自身免疫过程中发挥作用。
Rheumatoid arthritis is a chronic autoimmune inflammatory disease with a complex genetic etiology. Members of the signaling lymphocyte activation molecule (SLAM) family carry out pivotal functions in innate immunity and in conventional lymphocytes. We identified a linkage disequilibrium block associated with rheumatoid arthritis in the chromosome 1q region containing multiple SLAM family genes. In this block, the association peaked at two functional SNPs (rs3766379 and rs6682654) in CD244 in two independent rheumatoid arthritis cohorts from Japan (P = 3.23 x 10(-8) and P = 7.45 x 10(-8)). We also identified a Japanese cohort with systemic lupus erythematosus that had a similar genotype distribution as the rheumatoid arthritis cohorts. We demonstrated that the rheumatoid arthritis-susceptible alleles of rs3766379 and rs6682654 and their haplotype increased their expression in luciferase and allele-specific transcript quantification assays. CD244 is a genetic risk factor for rheumatoid arthritis and may have a role in the autoimmune process shared by rheumatoid arthritis and systemic lupus erythematosus.