Genes associated with rheumatic and diffuse collagen diseases

对风湿性和弥漫性胶原病包括类风湿性关节炎（RA）和系统性红斑狼疮（SLE）患者的基因组进行分析，发现几个基因与疾病相关。这些发现有助于阐明这些疾病的发病机制。(1)检测FCGR 2B与SLE的相关性。易感等位基因产物对B细胞活化的抑制作用较弱。(2)检测CD 72与肾炎阳性SLE的相关性。抗性单倍型产生更高水平的选择性剪接mRNA。(3)分析了几种TNF和TNF受体家族基因，并检测了BLyS和APRIL与SLE的相关性。APRIL易感等位基因产生较高的mRNA和蛋白水平。(4)NK受体基因NKG 2A、NKG 2C和CD 94与RA和SLE均无相关性，但NKG 2C缺失的单倍型频率高达20%。(5)KIR基因的存在/不存在多态性被证明与显微镜下多血管炎相关。(6)LILRB 1与HLA-DRB 1“共享表位”阳性RA相关。易感性单倍型表达较低水平的分子。(7)共发现20个基因在RA滑膜中表达上调。其中ID基因进一步进行体外功能分析。这些基因被发现是激活内皮细胞和血管生成所必需的。

Genome analyses of the patients with rheumatic and diffuse collagen diseases including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) were performed, and several genes were found to be associated with the diseases. These findings contribute to the elucidation of pathogenesis of these diseases. (1) Association between FCGR2B and SLE was detected. Susceptibility allele product showed a weaker inhibitory effect on B cell activation. (2) Association between CD72 and nephritis-positive SLE was detected. Resistant haplotype produced higher level of alternatively-spliced mRNA. (3) Several TNF and TNF receptor family genes were analyzed, and associations of BLyS and APRIL with SLE were detected. APRIL susceptibility allele produced higher level of mRNA and protein. (4) NK receptor genes including NKG2A, NKG2C and CD94 were not associated with RA nor SLE, but the frequency of NKG2C-deleted haplotype reached 20%. (5) Presence/absence polymorphism of KIR genes was shown to be associated with microscopic polyangitis. (6) Association of LILRB1 with HLA-DRB1 "shared epitope"-positive RA was detected. Susceptibility haplotype expressed lower level of the molecule. (7) A total of 20 genes were found to be up-regulated in RA synovium. in which ID genes were further subjected for in-vitro functional analyses. These genes were found to be essential for the activation of endothelial cells and angiogenesis.