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

Jennifer Pasquier, Mark Spurgeon, Martina Bradic, Binitha Thomas, Amal Robay, Omar Chidiac, Marie Joe DIb, Rebal Turjoman, Aleksandra Liberska, Michelle Staudt, Khalid Adnan Mohamed A. Fakhro, Robert Menzies, Amin Jayyousi, Mahmoud Zirie, Jassim Al Suwaidi, Rayaz Malik, Talal Talal, Arash Rafii Tabrizi, Jason Mezey, Juan Rodriguez-FloresRonald Crystal, Charbel Abi Khalil

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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.

Original languageEnglish
Pages (from-to)281-296
Number of pages16
JournalEpigenomics
Volume11
Issue number3
DOIs
Publication statusPublished - 1 Feb 2019

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Keywords

  • Charcot foot
  • diabetes
  • DNA methylation
  • epigenetics
  • epigenomics
  • gene expression
  • genetics

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

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