Relationship between Gene Polymorphism of Vascular Endothelial Growth Factor (VEGF) rs699947 with VEGF and Matrix Metalloproteinase-14 Protein Levels in Patient with Diabetic Foot Ulcer

Abstract

BACKGROUND: Vascular endothelial growth factor (VEGF) protein levels in diabetes mellitus (DM) patients with ulcerative foot will tend to decrease. Matrix metalloproteinases (MMPs) and their inhibitors have also been identified in regulating capillary tubes formation (morphogenesis) with the collagen matrix, associated with the formation and regression of granulation tissue during the wound healing process. AIM: This study was aimed to determine the relationship between gene polymorphism VEGF rs699947 with VEGF and MMP-14 protein levels in cases of diabetic foot ulcers (DFUs). METHODS: This study was an observational research with cross-sectional comparative study design. The population in this study were type-2 DM patients who met the inclusion criteria. According to the Meggitt-Wagner classification, the study sample was divided into two groups: Type 2 DM group without DFU and type 2 DM group with DFU Grades 1–3. RESULTS: In this study, there were differences in the protein levels of MMP-14 (p = 0.039) VEGF (p = 0.002) between type-2 DM patients with and without FDU. However, there was no difference in the VEGF gene polymorphism rs6999947 between type-2 DM patients with and without FDU (p = 0.099). In addition, the results showed that type-2 DM patients with MMP-14 protein levels ≤ 3.864 had a 3.6 times greater risk of suffer FDU compared to type-2 DM patients with MMP-14 protein levels > 3.864 but not significant (PR = 3.600 (IK 5 % 1.142–11.346); p = 0.052). Meanwhile, type 2 DM patients with VEGF protein levels ≤567.42 were significantly more at risk of 9048 times to suffer FDU compared to type 2 DM patients with VEGF protein levels > 567.42 (PR = 9.048 (CI 5% 2.571–31.842); p = 0.001). CONCLUSION: In type 2 DM patients with FDU, there were lower levels of MMP-14 and VEGF compared to patients without FDU. There is a significant relationship between VEGF protein levels and the incidence of FDU in type 2 DM patients, but there is no relationship between MMP-14 and the gene polymorphism VEGF rs6999947 with the incidence of FDU in type 2 DM patients.