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Mitochondrial DNA Copy Number in Peripheral Blood as a Potential Non-invasive Biomarker for Multiple Sclerosis.
NeuroMolecular Medicine ( IF 3.3 ) Pub Date : 2020-01-04 , DOI: 10.1007/s12017-019-08588-w
Ghada Al-Kafaji 1 , Halla F Bakheit 2 , Maram A Alharbi 3 , Ahmad A Farahat 4 , Mohamed Jailani 4 , Bashayer H Ebrahin 4 , Moiz Bakhiet 1
Affiliation  

The impaired mitochondrial function has been implicated in the pathogenicity of multiple sclerosis (MS), a chronic inflammatory, demyelinating, and neurodegenerative disease of the CNS. Circulating mtDNA copy number in body fluids has been proposed as an indicator for several neurodegenerative diseases, and the altered cerebrospinal fluid mtDNA has been shown as a promising marker for MS. The aim of this study was to determine changes and biomarker potential of circulating mtDNA in peripheral blood in MS. The mtDNA copy number was quantified by real-time PCR in blood samples from 60 patients with relapsing–remitting MS (RRMS) and 64 healthy controls. The RRMS patients had significantly lower circulating mtDNA copy number compared to controls. Subgroup analysis with stratification of RRMS patients based on disease duration under or over 10 years revealed that the mtDNA copy number was significantly lower in the group with longer disease duration. A negative correlation was observed between mtDNA copy number and disease duration. The ROC curve analysis indicated a significant ability of mtDNA copy number to separate RRMS patients from controls with an AUC of 0.859. This is the first study to measure peripheral blood mtDNA copy number in MS patients. Current data suggest that the reduction in peripheral blood mtDNA copy number may be an early event in MS and correlate with the disease progression. The findings of this study indicate that circulating blood-based mtDNA copy number may be a potential non-invasive candidate biomarker for mitochondria-mediated neurodegeneration and MS. This can put forward the clinical applicability over other invasive markers.

中文翻译:

外周血中的线粒体DNA拷贝数作为多发性硬化症的潜在非侵入性生物标志物。

线粒体功能受损与多发性硬化症(MS),CNS的慢性炎症,脱髓鞘和神经退行性疾病的致病性有关。体液中循环的mtDNA拷贝数已被提议作为多种神经退行性疾病的指标,而脑脊液mtDNA的改变已被证明是MS的有希望的标志。这项研究的目的是确定MS外周血中循环mtDNA的变化和生物标志物的潜力。通过实时PCR对来自60位复发缓解型MS(RRMS)患者和64位健康对照者的血液样本中的mtDNA拷贝数进行了定量。与对照相比,RRMS患者的循环mtDNA拷贝数明显降低。根据10年以下或10年以上疾病持续时间对RRMS患者进行分层的亚组分析显示,疾病持续时间较长的组中mtDNA拷贝数明显较低。mtDNA拷贝数与疾病持续时间之间呈负相关。ROC曲线分析表明,mtDNA拷贝数具有将RRMS患者与对照组(AUC为0.859)分开的显着能力。这是第一项测量MS患者外周血mtDNA拷贝数的研究。当前数据表明外周血mtDNA拷贝数的减少可能是MS的早期事件,并且与疾病进展相关。这项研究的发现表明,基于血液循环的mtDNA拷贝数可能是线粒体介导的神经变性和MS的潜在非侵入性候选生物标记。
更新日期:2020-01-04
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