Suzuki Akari, Yamada Ryo, Kochi Yuta, Sawada Tetsuji, Okada Yukinori, Matsuda Koichi, Kamatani Yoichiro, Mori Mikako, Shimane Kenichi, Hirabayashi Yasuhiko, Takahashi Atsushi, Tsunoda Tatsuhiko, Miyatake Akihiko, Kubo Michiaki, Kamatani Naoyuki, Nakamura Yusuke, Yamamoto Kazuhiko
Laboratory for Autoimmune Diseases, Center for Genomic Medicine, RIKEN, Yokohama, Kanagawa 230-0045, Japan.
Nat Genet. 2008 Oct;40(10):1224-9. doi: 10.1038/ng.205. Epub 2008 Sep 14.
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.
类风湿性关节炎是一种具有复杂遗传病因的慢性自身免疫性炎症疾病。信号淋巴细胞激活分子（SLAM）家族成员在先天免疫和传统淋巴细胞中发挥关键作用。我们在包含多个SLAM家族基因的1号染色体q区域鉴定出一个与类风湿性关节炎相关的连锁不平衡区域。在这个区域中，两个来自日本的独立类风湿性关节炎队列中，CD244基因的两个功能性单核苷酸多态性（rs3766379和rs6682654）的关联达到峰值（P = 3.23 x 10(-8)和P = 7.45 x 10(-8)）。我们还鉴定出一个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，rs3766379和rs6682654的类风湿性关节炎易感等位基因及其单倍型在荧光素酶和等位基因特异性转录定量分析中增加了它们的表达。CD244是类风湿性关节炎的一个遗传风险因素，可能在类风湿性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。
