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多发性硬化症患者全血样本中BDNF基因与BDNF-AS长链非编码RNA的表达分析:二者并非总是呈负相关

Expression Analysis of BDNF Gene and BDNF-AS Long Noncoding RNA in Whole Blood Samples of Multiple Sclerosis Patients: Not Always a Negative Correlation between Them.

作者信息

Gharzi Vajiheh, Gangi Maziar, Sayad Arezou, Mazdeh Mehrdokht, Arsang-Jang Shahram, Taheri Mohammad

机构信息

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.

出版信息

Iran J Allergy Asthma Immunol. 2018 Dec 4;17(6):548-556.

Abstract

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS), in which axonal damage is a deteriorative factor. Brain-Derived Neurotrophic Factor (BDNF) is described as a neuronal-survival gene, also capable of exerting pleiotropic effects on the immune cells. Here, we aimed to investigate expression levels of BDNF and its antisense RNA, BDNF-AS, in Iranian MS patients. Our case-control study was based on collecting 50 whole blood samples of relapsing-remitting MS patients and 50 healthy controls. Then, expression analysis of BDNF and BDNF-AS was performed by Real-time quantitative PCR. We found a strong and positive correlation between BDNF and BDNF-AS in MS patients. This is while no significant difference in BDNF and BDNF-AS expression levels was seen between MS patients and controls (p>0.05). A significant and strong positive correlation was found between the expression levels of BDNF-AS and BDNF (r=0.785, p<0.0001). Further, significant positive moderate correlations of BDNF and BDNF-AS with other lncRNAs (GSTT1-AS1 and IFNG-AS1) and genes (TNF and IFNG) were revealed (p<0.0001). Additionally, there was no correlation between the BDNF and BDNF-AS expressions and disease duration, age at onset, and Expanded Disability Status Scale of Kurtzke (EDSS) (p>0.05). BDNF and BDNF-AS expression levels revealed insignificant discrepancies in patients and controls. We found a strong and positive correlation between BDNF and BDNF-AS in MS patients, which is, based on previous studies, a quit novel finding and can be further discussed by future works to unravel its possible application in MS. We suggest evaluation of different leukocytes subsets separately along with large cohort studies comprising a higher number of individuals from different ages to unravel the effects of other possible aspects.

摘要

多发性硬化症(MS)是一种中枢神经系统(CNS)的慢性炎症性疾病,其中轴突损伤是一个恶化因素。脑源性神经营养因子(BDNF)被描述为一种神经元存活基因,也能够对免疫细胞发挥多效性作用。在此,我们旨在研究伊朗MS患者中BDNF及其反义RNA(BDNF-AS)的表达水平。我们的病例对照研究基于收集50份复发缓解型MS患者的全血样本和50份健康对照的全血样本。然后,通过实时定量PCR进行BDNF和BDNF-AS的表达分析。我们发现MS患者中BDNF和BDNF-AS之间存在强正相关。然而,MS患者与对照组之间BDNF和BDNF-AS的表达水平没有显著差异(p>0.05)。BDNF-AS和BDNF的表达水平之间存在显著的强正相关(r=0.785,p<0.0001)。此外,还揭示了BDNF和BDNF-AS与其他长链非编码RNA(GSTT1-AS1和IFNG-AS1)以及基因(TNF和IFNG)之间存在显著的正中度相关(p<0.0001)。此外,BDNF和BDNF-AS的表达与病程、发病年龄以及Kurtzke扩展残疾状态量表(EDSS)之间没有相关性(p>0.05)。BDNF和BDNF-AS的表达水平在患者和对照组中显示出不显著的差异。我们发现MS患者中BDNF和BDNF-AS之间存在强正相关,基于先前的研究,这是一个相当新颖的发现,未来的研究可以进一步探讨以揭示其在MS中的可能应用。我们建议分别评估不同的白细胞亚群,并开展大规模队列研究,纳入更多不同年龄的个体,以揭示其他可能因素的影响。

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