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
Keywords:Vascular endothelial growth factor, Diabetic foot, Type 2 diabetes mellitus, Wound healing, Matrix metalloproteinase
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.
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Al-Lawati JA. Diabetes mellitus: A local and global public health emergency! Oman Med J. 2017;32(3):177-9. https://doi.org/10.5001/omj.2017.34 PMid:28584596 DOI: https://doi.org/10.5001/omj.2017.34
Trikkalinou A, Papazafiropoulou AK, Melidonis A. Type 2 diabetes and quality of life. World J Diabetes. 2017;8(4):120-9. https://doi.org/10.4239/wjd.v8.i4.120 DOI: https://doi.org/10.4239/wjd.v8.i4.120
Li X, Lu Y, Wei P. Association between VEGF genetic variants and diabetic foot ulcer in Chinese Han population. Medicine (Baltimore). 2018;97(20):e10672. https://doi.org/10.1097/MD.0000000000010672 PMid:29768333 DOI: https://doi.org/10.1097/MD.0000000000010672
Armstrong DG, Boulton AJ, Bus SA. Diabetic foot ulcers and their recurrence. N Engl J Med. 2017;376:2367-75. https://doi.org/10.1056/nejmra1615439 PMid:28614678 DOI: https://doi.org/10.1056/NEJMra1615439
Amoli MM, Hasani-Ranjbar S, Roohipour N, Sayahpour FA, Amiri P, Zahedi P, et al. VEGF gene polymorphism association with diabetic foot ulcer. Diabetes Res Clin Pract. 2011;93(2):215-9. https://doi.org/10.1016/j.diabres.2011.04.016 PMid:21596454 DOI: https://doi.org/10.1016/j.diabres.2011.04.016
Qin Z, Fang W, Ma L, Wang Z, Yang YM, Lu YQ. VEGF levels in plasma in relation to metabolic control, inflammation, and microvascular complications in type-2 diabetes: A cohort study. Medicine (Baltimore). 2018;97(15):e0415. https://doi.org/10.1097/MD.0000000000010415 PMid:29642210 DOI: https://doi.org/10.1097/MD.0000000000010415
Ruthenborg RJ, Ban JJ, Wazir A, Takeda N, Kim JW. Regulation of wound healing and fibrosis by hypoxia and hypoxia-inducible factor-1. Mol Cells. 2014;37(9):637-43. https://doi.org/10.14348/molcells.2014.0150 PMid:24957212 DOI: https://doi.org/10.14348/molcells.2014.0150
Bowers SL, Kemp SS, Aguera KN, Koller GM, Forgy JC, Davis GE. Defining an upstream VEGF (vascular endothelial growth factor) priming signature for downstream factor-induced endothelial cell-pericyte tube network coassembly. Arterioscler Thromb Vasc Biol. 2020;40:2891-909. https://doi.org/10.1161/ATVBAHA.120.314517 PMid:33086871 DOI: https://doi.org/10.1161/ATVBAHA.120.314517
Imoukhuede PI, Popel AS. Expression of VEGF receptors on endothelial cells in mouse skeletal muscle. PLoS One. 2012;7(9):e44791. https://doi.org/10.1371/journal.pone.0044791 PMid:22984559 DOI: https://doi.org/10.1371/journal.pone.0044791
Kivela R, Hemanthakumar KA, Vaparanta K, Robciuc M, Izumiya Y, Kidoya H, et al. Endothelial cells regulate physiological cardiomyocite growth via VEGFR2-mediated paracrine signaling. Circulation. 2019;139:2570-84. https://doi.org/10.1161/CIRCULATIONAHA.118.036099 PMid:30922063 DOI: https://doi.org/10.1161/CIRCULATIONAHA.118.036099
Liao XH, Xiang Y, Li H, Zheng DL, Xu Y, Yu CX, et al. VEGF-A stimulates STAT3 activity via nitrosylation of myocardin to regulate the expression of vascular smooth muscle cell differentiation markers. Sci Rep. 2017;7(1):2660. https://doi.org/10.1038/s41598-017-02907-6 PMid:28572685 DOI: https://doi.org/10.1038/s41598-017-02907-6
Chen Y, Ye L, Guan L, Fan P, Liu R, Chen J, et al. Physiological electric field works via the VEGF receptor to stimulate neovessel formation of vascular endothelial cells in a 3D environment. Biol Open. 2018;7(9):035204. https://doi.org/10.1242/bio.035204 PMid:30232195 DOI: https://doi.org/10.1242/bio.035204
Ramakrishnan S, Anand V, Roy S. Vascular endothelial growth factor signaling in hypoxia and inflammation. J Neuroimmune Pharmacol. 2014;9(2):142-60. https://doi.org/10.1007/s11481-014-9531-7 PMid:24610033 DOI: https://doi.org/10.1007/s11481-014-9531-7
Morfoisse F, Renaud E, Hantelys F, Prats AC, Gary-Susini B. Role of hypoxia and vascular endothelial growth factors in lymphangiogenesis. Mol Cell Oncol. 2014;1(1):e29907. https://doi.org/10.4161/mco.29907 PMid:27308316 DOI: https://doi.org/10.4161/mco.29907
Semadi NI. The role of VEGF and TNF-alpha on epithelialization of diabetic foot ulcers after hyperbaric oxygen therapy. Open Access Maced J Med Sci. 2019;7(19):3177-83. https://doi.org/10.3889/oamjms.2019.297 PMid:31949512 DOI: https://doi.org/10.3889/oamjms.2019.297
Zhang J, Guan M, Xie C, Luo X, Zhang Q, Xue Y. Increased growth factors play a role in wound healing promoted by noninvasive oxygen-ozone therapy in diabetic patients with foot ulcers. Oxid Med Cell Longev. 2014;2014:273475. https://doi.org/10.1155/2014/273475 PMid:25089169 DOI: https://doi.org/10.1155/2014/273475
Caley MP, Martins VL, O’Toole EA. Metalloproteinases and wound healing. Adv Wound Care (New Rochelle). 2015;4(4):225-34. https://doi.org/10.1089/wound.2014.0581 PMid:25945285 DOI: https://doi.org/10.1089/wound.2014.0581
Rousselle P, Beck K. Laminin 332 processing impacts cellular impacts cellular behavior. Cell Adh Migr. 2013;7(1):122-34. https://doi.org/10.4161/cam.23132 PMid:23263634 DOI: https://doi.org/10.4161/cam.23132
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Copyright (c) 2022 Ivan Kurniawan Bassar, Jamsari Jamsari, Ellyza Nasrul, Humaryanto Humaryanto (Author)
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