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.

BackgroundPrevious studies have indicated that nitric oxide synthase 2 (NOS2) genetic variations are involved in delayed fracture healing and fracture non-union. Whether these genetic variants associate with the development of osteomyelitis (OM) remains unclear. Here, we analyzed the potential relationships between NOS2 genetic variations and the risk of developing post-traumatic OM (PTOM) in a Chinese Han population.MethodsAltogether 704 participants, including 336 PTOM patients and 368 healthy controls, were genotyped of rs2297514 and rs2248814 of the NOS2 gene using the SNaPshot genotyping method.ResultsOutcomes showed that the frequency of allele C of rs2297514 in the patient group was significantly lower than that in the control group (48.7% vs. 54.5%, P = 0.029, OR = 0.792, 95% CI 0.642 – 0.976). In addition, significant associations were found between rs2297514 and susceptibility to PTOM by the recessive model (P = 0.007, OR = 0.633, 95% CI 0.453 – 0.884), and the homozygous model (P = 0.039, OR = 0.648, 95% CI 0.429 – 0.979). Moreover, patients with the CC genotype of rs2297514 had lower inflammatory biomarkers levels than the TT genotype, especially for the C-reactive protein (CRP) level (median: 4.1 mg/L vs. 8.9 mg/L, P = 0.027). However, no significant relationship was noted between rs2248814 and the risk of developing PTOM.ConclusionIn this Chinese cohort, rs2297514 is correlated with a decreased risk of PTOM development, with genotype CC as a protective factor.

Genetic variations in the solute carrier family 11 member 1 (SLC11A1) gene have been implicated in developing inflammatory disorders. However, it is still unclear whether such polymorphisms contribute to the pathogenesis of post‐traumatic osteomyelitis (PTOM). Therefore, this study investigated the roles of genetic variations of the SLC11A1 gene (rs17235409 and rs3731865) in PTOM development in a Chinese Han cohort. The SNaPshot method was used for genotyping 704 participants (336 patients and 368 controls) for rs17235409 and rs3731865. Outcomes revealed that rs17235409 increased the risk of PTOM occurrence by dominant (p = .037, odds ratio [OR] = 1.44) and heterozygous models (p = .035, OR = 1.45), implying AG genotype as a risk factor for PTOM development. In addition, patients with AG genotype had relatively higher levels of inflammatory biomarkers than those with AA and GG genotypes, especially for the white blood cell count and C‐reactive protein. Despite no statistically significant differences achieved, rs3731865 may reduce the PTOM susceptibility, suggested by the results of dominant (p = .051, OR = 0.67) and heterozygous (p = .068, OR = 0.69) models. In short, rs17235409 confers an elevated chance of developing PTOM, with AG genotype as a risk factor. Whether rs3731865 involves in the pathogenesis of PTOM requires further investigations.