Low level of plasma VEGF-A and C allele of -2578*C/A polymorphism in the VEGF-A gene are risk factors of diabetic foot ulcer in Javanese ethnic

https://doi.org/10.19106/JMedSci005302202106

Ika Rahayu(1*), Hemi Sinorita(2), Kris Herawan Timotius(3), Ahmad Hamim Sadewa(4)

(1) Department of Biochemistry, Faculty of Medicine, Universitas Kristen Krida Wacana, Jakarta/Research Center for Jamu and Herbal Medicine, Universitas Kristen Krida Wacana, Jakarta
(2) Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada / Dr.Sardjito General Hospital, Yogyakarta
(3) Department of Biochemistry, Faculty of Medicine, Universitas Kristen Krida Wacana, Jakarta/Research Center for Jamu and Herbal Medicine, Universitas Kristen Krida Wacana, Jakarta
(4) Department of Biochemistry, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
(*) Corresponding Author

Abstract


Diabetes mellitus (DM) is caused by abnormal insulin secretion, impaired
insulin action, or both. Approximately 12-25% of type 2 diabetes mellitus
(T2DM) patients will develop diabetic foot ulcers (DFU). Vascular endothelial
growth factor (VEGF) is a group of platelet-derived growth factors (PDGF)
which have a potential role in angiogenesis. Low levels of VEGF-A can cause
insufficient angiogenesis leading to wound healing inhibition. The 2578*C/A
polymorphism of VEGF-A gene has been reported as a candidate marker
for the DFU development. However, the variant role in the development of
DFU in Javanese ethnic needs to be clarified. This study was conducted to
compare VEGF-A levels and the -2578*C/A polymorphism of the VEGF gene
among diabetic patients with and without DFU in Javanese ethnic. In this
case-control study, the T2DM individuals with DFU as case group (n=19) and
without DFU as control group (n=41) were recruited. The VEGF-A levelswere
determined by ELISA. The ARMS-PCR technique was applied to investigate the
presence of -2578*C/A polymorphism of the VEGF gene. Data were analyzed
with independent t, Mann-Whitney, Chi-square, and Kruskal-Wallis tests with
significance level of p<0.05. The median of plasma VEGF-A level was significantly
different between case and control groups (p=0.001). The genotype frequency
of -2578*C/A polymorphism of VEGF gene was no difference between case and
control groups. However, individuals with C allele have a higher risk factor to
develop DFU than A allele (CC+CA vs AA;p=0.042; OR=2.5). The plasma VEGF-A
levels were lower in T2DM subjects with DFU than those without DFU. In
conclusion,individuals with C allele of -2578*C/A polymorphism of VEGF gene
are more susceptible to have DFU than individuals with A allele in Javanese
ethnic with T2DM.

Full Text:

PDF


References

  1. Anonim. Management of diabetic foot infections. Med Mal infect 2007; 37(1):14-25.
  2. Cavanagh PR, Lipsky BA, Bradbory AW, Botek G. Treatment for diabetic foot ulcers. Lancet 2005; 366(9498):1725-35. https://doi.org/10.1016/S0140-6736(05)67699-4
  3. Pendsey S. Epidemiologi aspects of diabetic foot. Int J Diab Dev Countries 1994; 14:37-8.
  4. International Diabetes Federation. IDF diabetes atlas 7th ed. 2015. www.idf.org/diabetesatlas
  5. Hena J, Growther L. Studies on bacterial infections of diabetic foot ulcer. Afr J Cln Expert Microbiol 2010; 11(3):146-9.
  6. Tonnesen MG, Feng X, Clark RA. Angiogenesis in wound healing. J Investig Dermatol Symp Proc 2000; 5(1)1:40-6. https://doi.org/10.1046/j.1087-0024.2000.00014.x
  7. Wilgus TA, DiPietro LA. Complex roles for VEGF in dermal wound healing. J Invest Dermatol 2012; 132(2):493-4. https://doi.org/10.1038/jid.2011.343
  8. Brogan IJ, Khan N, Isaac K, Hutchinson JA, Pravica V, Hutchinson IV. Novel polymorphism in the promoter and 5' UTR regions of human vascular endothelial growth factor gene. 1999. In: Shahbazi M, Fryer AA, Pravica V, Brogan IJ, Ramsay HM, Hutchinson IV et al. Vascular endothelial growth factor gene polymorphisms are associated with acute renal allograft rejection. J Am Soc Nephrol 2002; 13:260-4.
  9. Marsh S, Nakhoul FM, Skorecki K, Rubin A, Miller BP, Leibu R, et al. Hypoxic induction of vascular endothelial growth factor is marked decreased in diabetic individuals who do not develop retinopathy. Diabetes Care 2000; 23(9):1375-80. https://doi.org/10.2337/diacare.23.9.1375
  10. Rivard A, Silver M, Chen D, Kearney M, Magner M, Annex B et al. Rescue of diabetes-related impairment of angiogenesis by intramuscular gene therapy with adeno-VEGF. Am J Pathol 1999; 154(2):355-63. https://doi.org/10.1016/S0002-9440(10)65282-0
  11. 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
  12. Shahbazi M, Fryer AA, Pravica V, Brogan IJ, Ramsay HM, Hutchinson IV et al. Vascular endothelial growth factor gene polymorphisms are associated with acute renal allograft rejection. J Am Soc Nephrol 2002; 13(1):260-4.
  13. Hoong SL, Blann AD, Aun YC, Freestone B, Lip GYH. Plasma vascular endothelial growth factor, angiopoietin-1, and angiopoietin-2 in diabetes. Diabetes Care 2004; 27(12):2918-24. https://doi.org/10.2337/diacare.27.12.2918
  14. Kusumanto YH, Meijer C, Dam W, Mulder NH, Hospers GAP. Circulating vascular endothelial growth factor (VEGF) levels in advanced stage cancer patient compared to normal controls and diabetes mellitus patients with critical ischemia. Drug Target Insight 2007; 2:105-9.
  15. Al-Habboubi H, Sater MS, Almawi AW, Al-Khateeb GM, Almawi WY. Contribution of VEGF polymorphism to variation in VEGF serum level in a healthy population. Eur Cytokine Netw 2011; 22(3):154-8. https://doi.org/10.1684/ecn.2011.0289
  16. Guerzoni AR, Biselli PM, de Godoy MF, Souza DRS, Haddad R, Eberlin MN et al. Homocysteine and MTHFR and VEGF gene polymorphism: Impact on coronary artery disease. Aq Bras Cardiol 2009; 92(4):249-54. https://doi.org/10.1590/s0066-782x2009000400003
  17. Ruggiero D, Dalmasso C, Nutile T, Sorice R, Dionisi L, Aversano M et al. Genetic of VEGF serum variation in human isolated populations of Cilento: Importance of VEGF polymorphism. PloS One 2011; 6(2):e16982. https://doi.org/10.1371/journal.pone.0016982
  18. Habibi I, Sfar I, Chebil A, Kort F, Bouraoui R, Jendoubi-Ayed S et al. Vascular endothelial growth factor genetic polymorphism and susceptibility to age-related macular degeneration in Tunisian population. Biomarker Res 2014; 2:15. https://doi.org/10.1186/2050-7771-2-15
  19. Freathy RM, Weedon MN, Shields B, Hitman GA, Walker M, McCarthy MI et al. Functional variation in VEGF is not associated with type 2 diabetes in a United Kingdom caucasian population. JOP 2006; 7(3):295-302.
  20. Fukumura D, Xavier R, Sugiura T, Yi C, Eun-Chung P, Naifang L et al. Tumor induction of VEGF promoter activity in stromal cells. Cell 1998; 94(6):715-25. https://doi.org/10.1016/S0092-8674(00)81731-6
  21. Bhanoori M, Babu KA, Reddy NGP, Rao KL, Zondervan K, Deenadayal M et al. The vascular endothelial growth factor (VEGF) 1405G>C 50-untranslated region polymorphism and increased risk of endometriosis in South Indian women: a case control study. Hum Reprod 2005; 20(7):1844-9. https://doi.org/10.1093/humrep/deh852
  22. Natarajan R, Bai W, Lanting L, Gonzales, Nadler J. Effect of high glucose on vascular endothelial growth factor expression in vascular smooth muscle cells. Am J Physiol 1997; 273(35):H2224-31. https://doi.org/10.1152/ajpheart.1997.273.5.H2224
  23. Tilton RG, Kawamura T, Chang KC, Ido Y, Bjercke RJ, Stephan CC et al. Vascular endothelial growth factor induced by elevated glucose levesl in rats is mediated by vascular endothelial growth factor. J clin Invest 1997; 99(9):2192-022. https://doi.org/10.1172/JCI119392
  24. Tellechea A, Leal E, Veves A, Carvalho E. Inflammatory and angiogenic abnormalities in diabetic wound healing: Role of neuropeptides and therapeutic perspectives. CircVasc J 2010; 3:43-55. https://doi.org/10.2174/1874382601003010043
  25. Brem H, Kodra A, Golinko MS, Entero H, Stojadinovic O, Wang VM et al. Mechanism of sustained release of vascular endothelial growth factor in accelerating experimental diabetic healing. J Invest Dermatol 2009; 129(9):2275-87. https://doi.org/10.1038/jid.2009.26
  26. Li JJ, Huang YQ, Basch R, Karpatkin S. Thrombin induces the release of angiopoietin-1 from platelets.2001. In: Tellechea A, Leal E, Veves A, Carvalho E. Inflammatory and angiogenic abnormalities in diabetic wound healing : Role of neuropeptides and therapeutic perspectives. CircVasc J. 2010; 3:43-55.
  27. Veves A, King GL. Can VEGF reverse diabetic neuropathy in human subjects? J Clin Invest 2001; 107(10):1215-8. https://doi.org/10.1172/JCI13038
  28. Rodrigues J, Mitta N. Diabetic foot and gangrene. 2011. In: Vitin A. (Ed). Gangrene-current concept and management options, pp 121–144. Available from: URL: http://www.intechopen.com.
  29. Falanga V. Wound healing and its impairment in the diabetic foot. Lancet 2005; 366(9498):1736-43. https://doi.org/10.1016/S0140-6736(05)67700-8
  30. Galkowska H, Olszewski WL, Wojewodzka U, Rosinski G, Karnafel W. Neurogenic factors in the impaired healing of diabetic foot ulcer. J Surg Res 2006; 134(2):252-8. https://doi.org/10.1016/j.jss.2006.02.006



DOI: https://doi.org/10.19106/JMedSci005302202106

Article Metrics

Abstract views : 1214 | views : 1849


Bookmark and Share


Copyright (c) 2021 Ika Rahayu, Hemi Sinorita, Kris Herawan Timotius, Ahmad Hamim Sadewa

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.