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多发性硬化症患者中参与 CD4+ 细胞活化的 miRNAs 的表达和遗传分析。

Expression and genetic analysis of miRNAs involved in CD4+ cell activation in patients with multiple sclerosis.

机构信息

Department of Neurological Sciences, Dino Ferrari Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.

出版信息

Neurosci Lett. 2011 Oct 17;504(1):9-12. doi: 10.1016/j.neulet.2011.08.021. Epub 2011 Aug 19.

DOI:10.1016/j.neulet.2011.08.021
PMID:21875645
Abstract

MicroRNA (miRNA)-mediate RNA interference has been identified as a novel mechanism that regulates protein expression. It is recognised that miRNAs play essential roles in the immune system and for correct function in the brain. Moreover, it is now clear that abnormal miRNA expression is a common feature of several diseases involving the immune system including multiple sclerosis (MS). Expression analysis for miR-21, miR-146a and -b, miR-150, miR-155 was carried out in peripheral mononuclear cells (PBMC) from a cohort of 29 MS patients and 19 controls. Subsequently, a case control study for miR-146 rs2910164 variant was performed in an overall population of 346 MS cases and 339 controls. A statistically significant increased expression of miR-21, miR-146a and -b was observed in relapsing remitting (RR)MS patients as compared with controls (1.44±0.13 vs 0.79±0.06, P=0.036; 1.50±0.12 vs 0.84±0.08, P=0.039; 1.54±0.15 vs 0.72±0.08, P=0.001 respectively). On the contrary, no differences were found in the expression levels of both miR-150 and miR-155 in patients as compared with controls (P>0.05). The genetic association study failed to find any differences in the frequencies of rs2910164 between patients and controls. miRNA dysregulation may contribute to the pathogenesis of MS and highlights the possibility to define different disease entities with specific miRNAs profile.

摘要

微小 RNA (miRNA)-介导的 RNA 干扰已被确定为一种新的调节蛋白质表达的机制。人们认识到,miRNAs 在免疫系统中发挥着重要作用,对大脑的正常功能也至关重要。此外,现在很清楚,异常的 miRNA 表达是几种涉及免疫系统的疾病的共同特征,包括多发性硬化症 (MS)。在 29 名 MS 患者和 19 名对照者的外周单核细胞 (PBMC) 中进行了 miR-21、miR-146a 和 -b、miR-150、miR-155 的表达分析。随后,在总共 346 名 MS 病例和 339 名对照者的人群中进行了 miR-146 rs2910164 变体的病例对照研究。与对照组相比,缓解复发型 (RR) MS 患者的 miR-21、miR-146a 和 -b 的表达显著升高(1.44±0.13 比 0.79±0.06,P=0.036;1.50±0.12 比 0.84±0.08,P=0.039;1.54±0.15 比 0.72±0.08,P=0.001)。相反,与对照组相比,患者 miR-150 和 miR-155 的表达水平没有差异(P>0.05)。遗传关联研究未发现 rs2910164 频率在患者和对照组之间存在差异。miRNA 失调可能有助于 MS 的发病机制,并强调了使用特定 miRNA 谱定义不同疾病实体的可能性。

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