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急性糖尿病夏科氏足症患者循环单核细胞的全甲基化组分析显示,参与破骨细胞形成的差异甲基化基因。

Whole-methylome analysis of circulating monocytes in acute diabetic Charcot foot reveals differentially methylated genes involved in the formation of osteoclasts.

机构信息

Epigenetics Cardiovascular Laboratory, Department of Genetic Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar.

Stem Cell and Microenvironment Laboratory, Weill Cornell Medicine-Qatar, Doha, Qatar.

出版信息

Epigenomics. 2019 Feb;11(3):281-296. doi: 10.2217/epi-2018-0144. Epub 2018 Nov 1.

Abstract

AIM

To assess whether DNA methylation of monocytes play a role in the development of acute diabetic Charcot foot (CF).

PATIENTS & METHODS: We studied the whole methylome (WM) of circulating monocytes in 18 patients with Type 2 diabetes (T2D) and acute CF, 18 T2D patients with equivalent neuropathy and 18 T2D patients without neuropathy, using the enhanced reduced representation bisulfite sequencing technique.

RESULTS & CONCLUSION: WM analysis demonstrated that CF monocytes are differentially methylated compared with non-CF monocytes, in both CpG-site and gene-mapped analysis approaches. Among the methylated genes, several are involved in the migration process during monocyte differentiation into osteoclasts or are indirectly involved through the regulation of inflammatory pathways. Finally, we demonstrated an association between methylation and gene expression in cis- and trans-association.

摘要

目的

评估单核细胞的 DNA 甲基化是否在急性糖尿病性夏科足(CF)的发生发展中发挥作用。

患者与方法

我们采用增强型简化重亚硫酸盐测序技术,研究了 18 例 2 型糖尿病(T2D)合并急性 CF、18 例 T2D 合并等效神经病变和 18 例 T2D 无神经病变患者的循环单核细胞的全甲基组(WM)。

结果与结论

CpG 位点和基因映射分析方法均显示,CF 单核细胞与非 CF 单核细胞相比存在差异甲基化。在甲基化基因中,有几个基因参与单核细胞向破骨细胞分化过程中的迁移,或者通过调节炎症途径间接参与。最后,我们证明了顺式和反式关联中甲基化与基因表达之间存在关联。

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