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脑源性神经营养因子的血清水平及DNA甲基化状态与冠状动脉疾病严重程度的关联

Association of Serum Level and DNA Methylation Status of Brain-Derived Neurotrophic Factor with the Severity of Coronary Artery Disease.

作者信息

Esmaeili Fataneh, Mansouri Elaheh, Emami Mohammad Amin, Montazerghaem Hossein, Hosseini Teshnizi Saeed, Kheirandish Masoumeh, Koochakkhani Shabnaz, Eftekhar Ebrahim

机构信息

Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.

Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Indian J Clin Biochem. 2022 Apr;37(2):159-168. doi: 10.1007/s12291-021-00974-1. Epub 2021 Apr 12.

DOI:10.1007/s12291-021-00974-1
PMID:35463104
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8993966/
Abstract

New investigations suggest a pivotal role of brain-derived neurotrophic factor (BDNF) in cardiovascular homeostasis. However, no data could indicate the association between BDNF methylation status and the risk of coronary artery disease (CAD). The aim of the present study was to assess the association of BDNF methylation status and its serum level with the severity of CAD. According to the angiography report, a total of 84 non-diabetic CAD patients with at least 50% stenosis in one of the major coronary arteries were selected as the CAD group. For comparison, 62 angiographically proven non-CAD participants were selected as control. Additionally, subjects were categorized according to the Gensini Scoring system. Blood sample was used for genomic DNA isolation. Methylation status of the BDNF gene in exonic region was determined using the MS-PCR method and serum BDNF levels were measured with ELISA. BDNF gene methylation was significantly higher in the CAD group than in the non-CAD group. After adjustment for confounding factors, BDNF gene hypermethylation increases the risk of CAD in the total population (OR = 2.769; 95% CI, 1.033-7.423;  = 0.043). BDNF gene hypermethylation was higher in patients with severe CAD than patients with mild CAD. Additionally, the serum BDNF level was not different from non-diabetic CAD and control groups. Our findings indicate that BDNF hypermethylation was associated with an increased risk of CAD, which may help identify subjects being at the risk of developing CAD. In addition, BDNF hypermethylation shows a significant correlation with the severity of CAD.

摘要

新的研究表明,脑源性神经营养因子(BDNF)在心血管稳态中起关键作用。然而,尚无数据表明BDNF甲基化状态与冠状动脉疾病(CAD)风险之间的关联。本研究的目的是评估BDNF甲基化状态及其血清水平与CAD严重程度之间的关联。根据血管造影报告,选取84例主要冠状动脉之一至少有50%狭窄的非糖尿病CAD患者作为CAD组。为作比较,选取62例经血管造影证实的非CAD参与者作为对照组。此外,根据Gensini评分系统对受试者进行分类。采集血样用于分离基因组DNA。采用甲基化特异性聚合酶链反应(MS-PCR)法测定BDNF基因外显子区域的甲基化状态,并用酶联免疫吸附测定(ELISA)法检测血清BDNF水平。CAD组的BDNF基因甲基化显著高于非CAD组。在对混杂因素进行校正后,BDNF基因高甲基化增加了总体人群患CAD的风险(比值比[OR]=2.769;95%置信区间[CI],1.033 - 7.423;P=0.043)。重度CAD患者的BDNF基因高甲基化高于轻度CAD患者。此外,非糖尿病CAD组和对照组的血清BDNF水平无差异。我们的研究结果表明,BDNF高甲基化与CAD风险增加相关,这可能有助于识别有患CAD风险的受试者。此外,BDNF高甲基化与CAD的严重程度显著相关。

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