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

1.鉴定了编码B淋巴细胞抑制性受体FCGR2B Ile232Thr跨膜区氨基酸取代的SNP。在3个亚洲人群中，系统性红斑狼疮(SLE)患者的232Thr/Thr基因型显著增加。功能研究表明，232Thr等位基因产物在膜脂筏中的定位减少，并且232Thr产物传递的抑制信号弱于232Ile产物。2.鉴定了人CD72的两种主要单倍型。其中一种单倍型与另一种剪接异构体的增加有关，在这种剪接异构体中，细胞外区发生了实质性的变化。这种单倍型与SLE患者对肾炎的保护作用有关。此外，在CD72单倍型的存在下，FCGR2B-232Thr的风险通过上位性相互作用显著降低。3.发现启动子SNP与CD1…的表达增加有关BLYS(BAFF)、APRIL及其受体BAFF-R、TACI和BCMA具有一定的多态性。在日本和荷兰人群中，NKG2C缺失的单倍型普遍存在，单倍型频率分别为20.2%和20.0%。6.LILRB1(ILT2，LIR1)基因高度多态，其中一种单倍型与类风湿性关节炎(RA)易感性有关。7.研究发现日本和荷兰人群中存在HLADRB1^*0901-DQB1^*0303单倍型和KIR基因与日本微小多血管炎患者的相关性。研究发现，在血管内皮生长因子诱导的人脐静脉内皮细胞内皮细胞活化和血管生成特性中，ID是必不可少的。较少

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