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冠状动脉粥样硬化患者白细胞介素-6基因启动子区低甲基化CpG岛与IL-6 mRNA水平的关系

Relationship of hypomethylation CpG islands in interleukin-6 gene promoter with IL-6 mRNA levels in patients with coronary atherosclerosis.

作者信息

Mohammadpanah Monireh, Heidari Mohammad Mehdi, Khatami Mehri, Hadadzadeh Mehdi

机构信息

Department of Biology, Faculty of Science, Yazd University, Yazd, Iran.

Department of Cardiac Surgery, Afshar Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

出版信息

J Cardiovasc Thorac Res. 2020;12(3):214-221. doi: 10.34172/jcvtr.2020.37. Epub 2020 Sep 5.

DOI:10.34172/jcvtr.2020.37
PMID:33123328
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7581844/
Abstract

Atherosclerosis is the important cause of most cardiovascular diseases, with high prevalence and mortality. Atherosclerosis is not only a lipid metabolism disorder but also recently is defined as a chronic inflammatory disease. Several studies showed that interleukin-6 (IL-6) is involved in the pathogenesis of atherosclerosis. The aim of the present study is the examination of mRNA Levels and hypomethylation of promoter in atherosclerosis patients. In this assay, a total of 35 cases with atherosclerosis and 30 controls were enrolled. RNA and DNA were isolated from the peripheral blood of all samples. Mean gene expression was determined by RT-PCR and methylation status at six CpG motifs in promoter was determined using bisulfite genomic sequencing. Real Time-PCR analysis results showed the mean IL6 RNA level in atherosclerosis patients candidate for CABG (coronary artery bypass grafting) was significantly higher than controls ( value = 0.01). Also, the upstream CpG motifs (-1038 to -952) in promoter were predominantly unmethylated in patients than in the controls ( value = 0.01). These findings suggest that an increase in gene expression and its DNA hypomethylation promoter are associated with atherosclerosis patient's candidate for CABG surgery.

摘要

动脉粥样硬化是大多数心血管疾病的重要病因,具有高患病率和死亡率。动脉粥样硬化不仅是一种脂质代谢紊乱,而且最近被定义为一种慢性炎症性疾病。多项研究表明,白细胞介素-6(IL-6)参与动脉粥样硬化的发病机制。本研究的目的是检测动脉粥样硬化患者中mRNA水平和启动子的低甲基化情况。在该检测中,共纳入了35例动脉粥样硬化患者和30例对照。从所有样本的外周血中分离RNA和DNA。通过逆转录聚合酶链反应(RT-PCR)测定平均基因表达,并使用亚硫酸氢盐基因组测序法测定启动子中六个CpG基序的甲基化状态。实时聚合酶链反应(Real Time-PCR)分析结果显示,冠状动脉旁路移植术(CABG)候选动脉粥样硬化患者的平均IL6 RNA水平显著高于对照组(P值 = 0.01)。此外,患者启动子中的上游CpG基序(-1038至-952)比对照组更主要地处于未甲基化状态(P值 = 0.01)。这些发现表明,基因表达增加及其启动子的DNA低甲基化与CABG手术候选动脉粥样硬化患者相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c2c/7581844/0461c24a242f/jcvtr-12-214-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c2c/7581844/f83bc3d20ac5/jcvtr-12-214-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c2c/7581844/731f99f11ed7/jcvtr-12-214-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c2c/7581844/52f4d1d3a5eb/jcvtr-12-214-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c2c/7581844/b4ceecd35956/jcvtr-12-214-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c2c/7581844/0461c24a242f/jcvtr-12-214-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c2c/7581844/f83bc3d20ac5/jcvtr-12-214-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c2c/7581844/731f99f11ed7/jcvtr-12-214-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c2c/7581844/52f4d1d3a5eb/jcvtr-12-214-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c2c/7581844/b4ceecd35956/jcvtr-12-214-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c2c/7581844/0461c24a242f/jcvtr-12-214-g005.jpg

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