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ChREBP 基因甲基化与 2 型糖尿病病理学特征的相关性。

Correlation of ChREBP Gene Methylation with Pathological Characteristics of Type 2 Diabetes Mellitus.

机构信息

Department of General Medicine, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, 010000, China.

出版信息

Appl Biochem Biotechnol. 2024 Jun;196(6):3076-3087. doi: 10.1007/s12010-023-04714-4. Epub 2023 Aug 24.

DOI:10.1007/s12010-023-04714-4
PMID:37615853
Abstract

The objective of this study is to investigate the expression of the carbohydrate response element binding protein (ChREBP) gene in type 2 diabetes mellitus (T2DM) and its correlation with pathological features. For obtaining and exploring the pathological features in patients, sixty T2DM patients (the research group) and thirty healthy controls (the control group) presented to our hospital between January 2019 and June 2019 were selected as the research participants. After DNA extraction from peripheral blood mononuclear cells (PBMCs) and modification of target gene methylation with bisulfite, differences in methylation were verified, and the correlation of ChREBP methylation level with T2DM pathological features and single nucleotide polymorphism (SNP) typing was discussed. According to the prediction results of UCSC Genome Browser Home, there were two CpG islands in the promoter region of the ChREBP gene, and the first exon was selected for research. The ChREBP methylation rate was statistically higher in the research group versus the control group (P < 0.05). Age, FPG, TC, and TG were confirmed by the multiple linear regression analysis to be correlated with the ChREBP methylation rate (P < 0.05). Finally, there was no difference in ChREBP methylation level between CT- and CC-type patients at rs17145750 and rs1051921 loci (P > 0.05). Peripheral blood ChREBP methylation is elevated in T2DM patients and is closely related to age, blood glucose, and blood-lipid level, which is expected to be a new direction for future T2DM diagnosis and treatment.

摘要

本研究旨在探讨碳水化合物反应元件结合蛋白(ChREBP)基因在 2 型糖尿病(T2DM)中的表达及其与病理特征的相关性。为了获取和探索患者的病理特征,我们选择了 2019 年 1 月至 2019 年 6 月期间在我院就诊的 60 例 T2DM 患者(研究组)和 30 名健康对照者(对照组)作为研究对象。从外周血单个核细胞(PBMCs)中提取 DNA,用亚硫酸氢盐对靶基因进行修饰后,验证了甲基化的差异,并讨论了 ChREBP 甲基化水平与 T2DM 病理特征和单核苷酸多态性(SNP)分型的相关性。根据 UCSC Genome Browser Home 的预测结果,ChREBP 基因启动子区有两个 CpG 岛,选择第一外显子进行研究。研究组的 ChREBP 甲基化率明显高于对照组(P<0.05)。多元线性回归分析证实年龄、FPG、TC 和 TG 与 ChREBP 甲基化率相关(P<0.05)。最后,在 rs17145750 和 rs1051921 位点,CT 和 CC 型患者的 ChREBP 甲基化水平无差异(P>0.05)。T2DM 患者外周血 ChREBP 甲基化水平升高,与年龄、血糖和血脂水平密切相关,有望成为未来 T2DM 诊断和治疗的新方向。

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本文引用的文献

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DPP-4 inhibitors for treating T2DM - hype or hope? an analysis based on the current literature.用于治疗2型糖尿病的二肽基肽酶-4抑制剂——炒作还是希望?基于当前文献的分析
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2 型糖尿病的治疗:挑战、希望和预期的成功。
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Reduced Bisulfite Sequencing: Quantitative Base-Resolution Sequencing of 5-Formylcytosine.简化亚硫酸氢盐测序:5-甲酰基胞嘧啶的定量碱基分辨率测序
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Adaptive and maladaptive roles for ChREBP in the liver and pancreatic islets.ChREBP在肝脏和胰岛中的适应性和适应不良作用。
J Biol Chem. 2021 Jan-Jun;296:100623. doi: 10.1016/j.jbc.2021.100623. Epub 2021 Apr 2.
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Diagnosis and management of diabetes insipidus for the internist: an update.内科医生对尿崩症的诊断与管理:最新进展
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7
ChREBP-Mediated Regulation of Lipid Metabolism: Involvement of the Gut Microbiota, Liver, and Adipose Tissue.ChREBP 介导的脂质代谢调控:涉及肠道微生物群、肝脏和脂肪组织。
Front Endocrinol (Lausanne). 2020 Dec 3;11:587189. doi: 10.3389/fendo.2020.587189. eCollection 2020.
8
Causative and Sanative dynamicity of ChREBP in Hepato-Metabolic disorders.ChREBP 在肝代谢紊乱中的因果和治疗动态。
Eur J Cell Biol. 2020 Nov;99(8):151128. doi: 10.1016/j.ejcb.2020.151128. Epub 2020 Nov 2.
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Targeted bisulfite sequencing for biomarker discovery.靶向亚硫酸氢盐测序用于生物标志物发现。
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The role of DNA methylation in the pathogenesis of type 2 diabetes mellitus.DNA 甲基化在 2 型糖尿病发病机制中的作用。
Clin Epigenetics. 2020 Jul 11;12(1):104. doi: 10.1186/s13148-020-00896-4.