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2 型糖尿病患者的高血糖会影响基因中特定 CpG 位点的甲基化。

Methylation of Specific CpG Sites in Genes is Affected by Hyperglycaemia in Type 2 Diabetic Patients.

机构信息

Department of Cell and Molecular Biology, Faculty of Biology, College of Science, University of Tehran, Tehran, Iran.

出版信息

Immunol Invest. 2020 Apr;49(3):287-298. doi: 10.1080/08820139.2019.1656227. Epub 2019 Sep 3.

DOI:10.1080/08820139.2019.1656227
PMID:31476928
Abstract

: Type 2 diabetes (T2D), which is the most common metabolic disorder in the world, results from insulin resistance of target tissues and reduced production of insulin from pancreatic cells with genetic and environmental factors both playing roles in the pathogenesis. The aim of this study was to investigate the effect of blood glucose levels on DNA methylation of and genes in the peripheral blood mononuclear cells (PBMCs) of non-diabetic, type 2 pre-diabetic and diabetic individuals.: In this case-control study, 54 non-diabetic, pre-diabetic and type 2 diabetic individuals were enrolled and categorized based on their fasting plasma glucose (FPG) and glycated hemoglobin (A1C) levels. DNA was extracted from PBMCs and subjected to bisulfite treatment. The methylation status of two CpG sites in the gene and three CpG sites in gene was then determined using Sanger sequencing.: Our results show that the methylation of gene is decreased and the methylation of gene is increased in diabetic individuals with hyperglycemia. Further analysis revealed that both CpG sites in gene are affected by hyperglycemia and display decreased methylation while only one CpG site in gene is affected by hyperglycemia.: We propose that the DNA methylation status of the CpG sites cg18773937 and cg23149881 in gene and the CpG site cg13399261 in gene could serve as an epigenetic marker of chronic inflammation and T2D development. These CpG sites can also be considered for studies on metabolic memory.

摘要

2 型糖尿病(T2D)是世界上最常见的代谢紊乱疾病,它是由靶组织胰岛素抵抗和胰腺β细胞胰岛素产生减少引起的,遗传和环境因素都在发病机制中起作用。本研究旨在探讨血糖水平对非糖尿病、2 型糖尿病前期和糖尿病个体外周血单个核细胞(PBMCs)中 和 基因 DNA 甲基化的影响。

在这项病例对照研究中,我们招募了 54 名非糖尿病、糖尿病前期和 2 型糖尿病个体,并根据他们的空腹血浆葡萄糖(FPG)和糖化血红蛋白(A1C)水平进行分类。从 PBMCs 中提取 DNA,并进行亚硫酸氢盐处理。然后使用 Sanger 测序法测定 基因中两个 CpG 位点和 基因中三个 CpG 位点的甲基化状态。

我们的研究结果表明,高血糖的糖尿病个体中 基因的甲基化降低,而 基因的甲基化增加。进一步的分析表明, 基因的两个 CpG 位点都受到高血糖的影响,表现为甲基化降低,而 基因的一个 CpG 位点仅受到高血糖的影响。

我们提出, 基因中 cg18773937 和 cg23149881 两个 CpG 位点和 基因中 cg13399261 位点的 DNA 甲基化状态可以作为慢性炎症和 T2D 发展的表观遗传标志物。这些 CpG 位点也可以考虑用于代谢记忆的研究。

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Immunol Invest. 2020 Apr;49(3):287-298. doi: 10.1080/08820139.2019.1656227. Epub 2019 Sep 3.
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