• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of molecular medicine: Official organ of the "Gesellschaft Deutscher Naturforscher und Arzte." >Gene expression and genotyping studies implicate the interleukin 7 receptor in the pathogenesis of primary progressive multiple sclerosis.
【24h】

Gene expression and genotyping studies implicate the interleukin 7 receptor in the pathogenesis of primary progressive multiple sclerosis.

机译：基因表达和基因分型研究表明白细胞介素7受体参与原发性进行性多发性硬化症的发病机制。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Multiple sclerosis (MS) is an enigmatic disease of the central nervous system resulting in sclerotic plaques with the pathological hallmarks of demyelination and axonal damage, which can be directly or indirectly orchestrated by cells from the peripheral circulation. The majority of patients with MS follow a relapsing-remitting course in the early stages of the disease (RRMS) but most ultimately enter a secondary progressive phase (SPMS). About 10% of patients follow a primary progressive course from the onset (PPMS). We measured gene expression in whole blood of people with and without chronic progressive MS (CPMS), PPMS and SPMS, to discover genes which may be differentially expressed in peripheral blood in active disease, and so identify pathologically significant genes and pathways; and we investigated genetic differences in the promoters of dysregulated genes encoded in genomic regions associated with MS. If SPMS and PPMS were independently compared to the controls, there was little overlap in theset of most dysregulated genes. Ribosomal protein genes, whose expression is usually associated with cell proliferation and activation, were dramatically over-represented in the set of most down-regulated genes in PPMS compared to SPMS (P<10(-4), chi(2)). The T cell proliferation gene IL7R (CD127) was also underexpressed in PPMS, but was up-regulated in SPMS compared to the controls. One interleukin 7 receptor (IL7R) promoter single nucleotide polymorphism (SNP), -504 C, was undertransmitted in PPMS trios (P=0.05, TDT), and carriers of this allele were under-represented in PPMS cases from two independent patient cohorts (combined P=0.006, FE). The four known IL7R promoter haplotypes were shown to have similar expression levels in healthy controls, but not in CPMS (P<0.01, t test). These data support the hypothesis that PPMS has significant pathogenetic differences from SPMS, and that IL7R may be a useful therapeutic target in PPMS.
机译：多发性硬化症（MS）是中枢神经系统的一种神秘疾病，会导致硬化斑块具有脱髓鞘和轴突损伤的病理特征，可以由周围循环的细胞直接或间接地进行编排。大多数MS患者在疾病早期（RRMS）遵循复发缓解过程，但大多数最终进入继发进行性阶段（SPMS）。约有10％的患者从发病（PPMS）开始就进行主要的进行性治疗。我们测量了患有和未患有慢性进行性MS（CPMS），PPMS和SPMS的人全血中的基因表达，以发现在活跃疾病中外周血中可能差异表达的基因，从而确定具有病理学意义的基因和途径。我们调查了与MS相关的基因组区域编码失调基因的启动子的遗传差异。如果将SPMS和PPMS与对照进行独立比较，则大多数失调基因的序列几乎没有重叠。核糖体蛋白基因的表达通常与细胞增殖和激活有关，与SPMS相比，PPMS中大多数下调的基因组中的核糖体蛋白基因显着过量（P <10（-4），chi（2））。 T细胞增殖基因IL7R（CD127）在PPMS中也表达不足，但与对照组相比在SPMS中上调。一个白细胞介素7受体（IL7R）启动子单核苷酸多态性（SNP）-504 C在PPMS三重奏中传播不足（P = 0.05，TDT），而在两个独立患者队列的PPMS病例中该等位基因的携带者表达不足（组合P = 0.006，FE）。已显示四种已知的IL7R启动子单倍型在健康对照中具有相似的表达水平，但在CPMS中则没有（P <0.01，t检验）。这些数据支持以下假设：PPMS与SPMS具有显着的致病性差异，并且IL7R可能是PPMS中有用的治疗靶标。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号