170-OR: Case-Control Study on Whole-Methylome Analysis of Monocytes in Acute Diabetic Charcot Foot-Identifying Differentially Methylated Genes

Introduction: Diabetic Charcot Foot (DCF) is a serious diabetes complication that damages bones and joints. Monocyte epigenetic modifications, notably DNA methylation, during DCF are unresolved. This study aims to analyze the whole-methylome of monocytes in acute DCF to identify differentially methylated genes involved in cell migration, differentiation, and osteoclast formation. Methods: In this case-control study, 30 patients with acute DCF and 30 matched healthy controls were recruited. Monocytes were isolated from peripheral blood samples, and DNA was extracted. Whole-methylome analysis was performed using bisulfite sequencing. Differentially methylated regions (DMRs) were identified and associated with genes involved in monocyte migration, differentiation, and osteoclast formation. Gene expression was further confirmed through qPCR. Results: Significant differences in methylation patterns were observed between DCF patients and controls. A total of 150 DMRs were identified, with 90 being hypomethylated and 60 hypermethylated in DCF patients. These regions were associated with genes crucial for monocyte function, including those involved in migration (e.g., CXCR4), differentiation (e.g., MAFB), and osteoclast formation (e.g., NFATC1). Gene expression analysis confirmed the upregulation of these genes in DCF patients compared to controls. Conclusion: This study determined that DCF monocytes had differently methylated genes involved in cell migration, differentiation, and osteoclast formation. These epigenetic alterations may contribute to DCF pathophysiology, providing treatment targets. Further study is needed to understand how these epigenetic modifications affect DCF progression and their potential as biomarkers or therapeutic targets.