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与多发性硬化症 HLA-DRB1 基因型相关的全基因组基因表达差异:一项初步研究。

Genome wide differences of gene expression associated with HLA-DRB1 genotype in multiple sclerosis: a pilot study.

机构信息

Department of Neurology and the M.I.N.D. Institute, University of California at Davis, Sacramento, CA 95817, USA.

出版信息

J Neuroimmunol. 2013 Apr 15;257(1-2):90-6. doi: 10.1016/j.jneuroim.2013.02.004. Epub 2013 Mar 9.

DOI:10.1016/j.jneuroim.2013.02.004
PMID:23477965
Abstract

Using two microarray platforms, we identify HLA-DRB5 as the most highly expressed gene in MS compared to healthy subjects. As expected, HLA-DRB5 expression was associated with the HLA-DRB11501 MS susceptibility allele. Besides HLA-DRB5, there were 1219 differentially expressed exons (p<0.01, |fold change (FC)|>1.2) that differed between HLA-DRB11501 Positive multiple sclerosis subjects (MSP) compared to HLA-DRB1*1501 negative multiple sclerosis subjects (MSN). Analysis of the regulated genes revealed significantly different immune signaling pathways including IL-4 and IL-17 in these two MS genotypes. Different risk alleles appear to be associated with different patterns of gene expression that may reflect differences in pathophysiology of these two MS subtypes. These preliminary data will need to be confirmed in future studies.

摘要

使用两种微阵列平台,我们确定与健康受试者相比,HLA-DRB5 是多发性硬化症中表达最高的基因。如预期的那样,HLA-DRB5 的表达与 HLA-DRB11501 多发性硬化症易感性等位基因相关。除了 HLA-DRB5 之外,在 HLA-DRB11501 阳性多发性硬化症患者 (MSP) 与 HLA-DRB1*1501 阴性多发性硬化症患者 (MSN) 之间还有 1219 个差异表达外显子 (p<0.01,|fold change (FC)|>1.2)。对调节基因的分析显示,这两种 MS 基因型中存在明显不同的免疫信号通路,包括 IL-4 和 IL-17。不同的风险等位基因似乎与不同的基因表达模式相关,这可能反映了这两种 MS 亚型的病理生理学差异。这些初步数据需要在未来的研究中得到证实。

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