Genomic studies on the rheumatic disease-related genes and their clinical implications

1.在B淋巴细胞抑制性受体FCGR 2 B Ile 232 Thr的跨膜区发现一个编码氨基酸替换的SNP。232 Thr/Thr基因型在三个亚洲人群的系统性红斑狼疮（SLE）中显著增加。功能研究显示232 Thr等位基因产物在膜脂筏上的定位减少，其传递的抑制信号弱于232 Ile。2.在人CD 72中发现了两种主要的单倍型。其中一个单倍型与可变剪接异构体的增加有关，其中胞外区发生了实质性改变。该单倍型与SLE患者的肾炎保护相关。此外，FCGR 2B-232 Thr所赋予的风险在该CD 72单倍型存在时通过上位性相互作用而显著降低。 ...更多信息 4.在BLyS（BAFF）、APRIL及其受体BAFF-R、TACI和BCMA中发现了多个多态性位点。APRIL基因的SNPs与日本人SLE易感性相关。5.日本和荷兰人群中普遍存在NKG 2C缺失的单倍型，单倍型频率分别为20.2%和20.0%。在日本和荷兰的普通人群中，纯合子缺陷率分别为4.1%和3.8%，这表明NKG 2C对生存或生殖不是必需的。（ILT 2，LIR 1）被发现是高度多态性，HLA-DRB 1共享表位阴性个体中，其中一种单倍型与类风湿关节炎（RA）易感性相关。7. HLA-DRB 1 ^*0901-DQB 1 ^*0303单倍型和KIR基因型与日本显微镜下多血管炎患者。8.Id基因在RA滑膜组织内的内皮细胞中过表达。Id被认为是必不可少的诱导内皮细胞活化和血管生成特性的VEGF在人脐静脉内皮细胞。少

1.A SNP coding for an amino acid substitution within the transmembrane domain of an inhibitory receptor of B lymphocytes, FCGR2B Ile232Thr, was identified. The genotype 232Thr/Thr was significantly increased in systemic lupus erythematosus (SLE) in three Asian populations. Functional studies revealed that localization of 232Thr allele product in membrane lipid raft was decreased, and the inhibitory signals transmitted from the 232Thr product were weaker than those from the 232Ile product.2.Two major haplotypes were identified in human CD72. One of the haplotypes was associated with increase of an alternative splicing isoform, in which extracellular region is substantially altered. This haplotype was associated with protection from nephritis in the patients with SLE. Moreover, the risk conferred by FCGR2B-232Thr was significantly decreased in the presence of this CD72haplotype through epistatic interaction.3.A promoter SNP was identified to be associated with increased expression of CD1 … More 9 and susceptibility to systemic sclerosis.4.A number of polymorphisms were identified in BLyS (BAFF), APRIL and their receptors, BAFF-R, TACI and BCMA. SNPs in APRIL were confirmed to be associated with susceptibility to SLE in Japanese.5.A haplotype with NKG2C deletion was found to be commonly present in the Japanese and Dutch populations, with haplotype frequencies of 20.2% and 20.0%, respectively. Homozygous deficiency was found in 4.1% and 3.8% in the Japanese and Dutch general populations, suggesting that NKG2C is not essential for survival or reproduction.6.LILRB1 (ILT2, LIR1) was found to be highly polymorphic, and one of the haplotypes was associated with susceptibility to rheumatoid arthritis (RA) in HLA-DRB1 shared epitope negative individuals.7.Association of HLA-DRB1^*0901-DQB1^*0303 haplotype and KIR genotypes with Japanese patients with microscopic polyangiitis was demonstrated.8.Id genes were overexpressed in the endothelial cells within RA synovial tissues. Id was found to be essential for the induction of endothelial cell activation and angiogenic properties by VEGF in human umbilical vein endothelial cells. Less