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World J Diabetes. Dec 15, 2022; 13(12): 1140-1153
Published online Dec 15, 2022. doi: 10.4239/wjd.v13.i12.1140
Single nucleotide variations in the development of diabetic foot ulcer: A narrative review
Yan-Jun Hu, Chen-Sheng Song, Nan Jiang
Yan-Jun Hu, Chen-Sheng Song, Nan Jiang, Division of Orthopaedics and Traumatology, Department of Orthopaedics, Southern Medical University Nanfang Hospital, Guangzhou 510515, Guangdong Province, China
Author contributions: Hu YJ and Song CS contributed equally to this study; Hu YJ and Jiang N conceived and designed the study; Song CS searched the literature; Song CS and Jiang N drafted the article; Hu YJ, Song CS, and Jiang N revised the manuscript; All authors approved the final version of the submitted article.
Supported by National Natural Science Foundation of China, No. 82172197; Guangdong Basic and Applied Basic Research Foundation, No. 2022A1515012385; and Guangdong Provincial Science and Technology Project, No. 2020A0505100039.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Nan Jiang, MD, Research Scientist, Surgeon, Division of Orthopaedics and Traumatology, Department of Orthopaedics, Southern Medical University Nanfang Hospital, No. 1838 Guangzhou Avenue North, Baiyun District, Guangzhou 510515, Guangdong Province, China. hnxyjn@smu.edu.cn
Received: August 27, 2022
Peer-review started: August 27, 2022
First decision: October 30, 2022
Revised: November 24, 2022
Accepted: December 5, 2022
Article in press: December 5, 2022
Published online: December 15, 2022
Processing time: 110 Days and 2.6 Hours
Abstract

Diabetes mellitus has become a global health problem, and the number of patients with diabetic foot ulcers (DFU) is rapidly increasing. Currently, DFU still poses great challenges to physicians, as the treatment is complex, with high risks of infection, recurrence, limb amputation, and even death. Therefore, a comprehensive understanding of DFU pathogenesis is of great importance. In this review, we summarized recent findings regarding the DFU development from the perspective of single-nucleotide variations (SNVs). Studies have shown that SNVs located in the genes encoding C-reactive protein, interleukin-6, tumor necrosis factor-alpha, stromal cell-derived factor-1, vascular endothelial growth factor, nuclear factor erythroid-2-related factor 2, sirtuin 1, intercellular adhesion molecule 1, monocyte chemoattractant protein-1, endothelial nitric oxide synthase, heat shock protein 70, hypoxia inducible factor 1 alpha, lysyl oxidase, intelectin 1, mitogen-activated protein kinase 14, toll-like receptors, osteoprotegerin, vitamin D receptor, and fibrinogen may be associated with the development of DFU. However, considering the limitations of the present investigations, future multi-center studies with larger sample sizes, as well as in-depth mechanistic research are warranted.

Keywords: Diabetic foot; Diabetic foot ulcer; Diabetic foot osteomyelitis; Single nucleotide variations; Narrative review

Core Tip: The pathogenesis of diabetic foot ulcer (DFU) is complex and is associated with both extrinsic and intrinsic factors. Most previous studies have reported the roles of external factors in DFU development and have neglected internal factors. In this narrative review, we focused on single-nucleotide variations (SNVs), as a representative of host factors. We summarized recent findings regarding the relationships between genetic SNVs and susceptibility of different populations to DFU. Future multicenter investigations with larger sample sizes, as well as in-depth mechanistic research, are necessary to better recognize and understand the roles of SNVs in DFU pathogenesis.