ISSN 2415-3060 (print), ISSN 2522-4972 (online)
  • 17 of 57
JMBS 2020, 5(1): 115–124
Clinical Medicine

The Role of Mononucleotide G634c VEGF-A Gene Polymorphism in Patients with Myocardial Infarction in Acute and Remote Periods

Kopytsa N. P., Kutya I. N., Hilova Ya.V.

The purpose of the research was to study the relationship of mononucleotide G634C VEGF-A gene polymorphism (rs 2010963) and factors of cardiovascular risk, degree of coronary damage, pattern of structural and functional changes of myocardium, course patients with ST-segment elevation myocardial infarction during hospital and remote (6 months) periods. Material and methods. 135 patients with STEMI were examined. There were 109 (80.7%) males and 26 (19.3%) females, with average age (59.21±8.92) years. The level of VEGF-A was determined with the help of enzyme immunoassay method by using the IBLINTERNATIONAL GMBH reagent kit, (Germany). Allelic G634C VEGF-A gene polymorphism (rs 2010963) was detected by using the polymerase chain reaction (PCR) method in real time. Blood for determination of VEGF-A level and genetic studies was collected on 5th day after ST-segment elevation myocardial infarction. Results and discussion. Genotype distribution of the polymorphic G634C VEGF-A gene (rs 2010963) in patients with ST segment elevation GIM had the following frequency: GG – 51.9%, GC – 47.4%, and CC – 0.7%. Further analysis was performed out in two groups: in patients with a GG-genotype (n=70) and with GC- and CC-genotypes (n=65). Patients with GC+СС genotypes had damaged anterior wall of left ventricle more frequently (р=0,022). Significant difference was detected in the occurrence of combined endpoint after 6 months of observation. Its frequency was significantly higher in the GC+CC-genotypes group (р=0,020). Significantly higher concentration of VEGF-A level was determined in the acute period of the disease in patients with GG-genotype: its level was 314.01 [159.94-627.66] pg/ml, and in GC+CC- genotypes group it was 221.28 [77.58- 440.82] pg/ml, (p = 0.045). In the acute period, there were significant differences in left ventricle end-diastolic volume (P=0.044) and left ventricle end-systolic volume (P=0.039) in the GC+CC-genotypes group. After 6 months no difference in the size of left ventricle cavity was detected. Univariate regression logistic analysis showed that VEGF-A levels in combination with GC+CC-genotypes, heredity, complicated anterior myocardial infarction. The latter could be predictors of adverse events within 6 months (P<0.0001). Conclusion. The patients with acute ST-segment elevation myocardial infarction had significantly higher levels of VEGF-A, and more expressed pronounced changes in left ventricular geometry in GG-genotype group compared to the GC+CC-genotypes group. VEGF-A level, GC+CC-genotypes and complicated course in acute period were high-sensitive predictors of adverse events within 6 months after ST-segment elevation myocardial infarction.

Keywords: acute ST-segment elevation myocardial infarction, vasculoendothelial growth factor-A (VEGF-A), G634C VEGF-A gene polymorphism (rs 2010963)

Full text: PDF (Ukr) 463K

  1. Bao P, Kodra A, Tomic-Canic M, Golinko MS, Ehrlich HP, Brem H. The role of vascular endothelial growth factor in wound healing. J Surg Res. 2009; 153: 347–58. PMID: 19027922 PMCID: PMC2728016.
  2. Hervas A, de Dios E, Forteza MJ, Miñana G, Nuñez J, Ruiz-Sauri A, et al. Intracoronary Infusion of Thioflavin-S to Study Microvascular Obstruction in a Model of Myocardial Infarction. Rev Esp Cardiol. 2015; 68(11): 928–34. PMID: 26253860.
  3. Hojo Y, Ikeda U, Zhu Y, Okada M, Ueno S, Arakawa H, et al. Expression of vascular endothelial growth factor in patients with acute myocardial infarction. J Am Coll Cardiol. 2000; 35: 968–73.
  4. Al-Habboubi HH, Sater MS, Almawi AW, Al-Khateeb GM, Almawi WY. Contribution of VEGF polymorphisms to variation in VEGF serum levels in a healthy population. Eur Cytokine Netw. 2011; 22(3): 154-8. PMID: 21982816.
  5. Watson CJ, Webb NJ, Bottomley MJ, Brenchley PE. C. Identification of polymorphisms within the vascular endothelial growth factor (VEGF) gene: correlation with variation in VEGF protein production. Cytokine. 2000; 12(8): 1232–5. PMID: 10930302.
  6. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. European Heart Journal. 2017; 66: 1–66. PMID: 28886621.
  7. Nakaz № 455 MOZ Ukrayiny vid 02.07.2014. Unifikovanyy klinichnyy protokol ekstrenoyi, pervynnoyi, vtorynnoyi (spetsializovanoyi) ta tretynnoyi (vysokospetsializovanoyi) medychnoyi dopomogy «Gostryy koronarnyy syndrom z elevatsiyeyu segmenta ST». Available from:
  8. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. ESC Scientific Document Group. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2016; 18: 891–975. PMID: 27206819.
  9. Williams B, Mancia G, Spiering W, Agabiti R E, Michel A, Michel B, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. European Heart Journal. 2018 Sep 1; 39(33): 3021–104. PMID: 30165516.
  10. Sutton J M, Scott CN. A prediction rоle for left ventricular dilatation post-MI? Europ Heart J. 2002; 23: 509-11. PMID: 11922636.
  11. Vander MР, De Boer RA , White HL, Van der Steege G, Hall AS, Voors AA, et al. The VEGF +405 CC promoter polymorphism is associated with an impaired prognosis in patients with chronic heart failure: a MERIT-HF substudy. J Card Fail. 2005; 11(4): 279-84. PMID: 15880336.
  12. Petrovic D, Verhovec R, Globocnik Petrovic M, Osredkar J, Peterlin B. Association of vascular endothelial growth factor gene polymorphism with myocardial infarction in patients with type 2 diabetes. Cardiology. 2007; 107(4): 291–5. PMID: 17264508.
  13. Olivier H, Stefano C, Selton-Suty C, Juillière Y, Donal E, Magne J, et al. Prediction of Left Ventricular Remodeling after a Myocardial Infarction: Role of Myocardial Deformation: A Systematic Review and Meta-Analysis. PLOS ONE. 2016 Dec 30. PMID: 28036335. PMCID: PMC5201304.
  14. Ebrahimian TG, Tamarat R, Clergue M, Duriez M, Levy BI, Silvestre JS. Dual effect of angiotensin-converting enzyme inhibition on angiogenesis in type 1 diabetic mice. Arterioscler Thromb Vasc Biol. 2005; 25(1): 65–70. PMID: 15528473.
  15. Ferroni P, Della-Morte D, Palmirotta R, Rundek T, Guadagni F, Roselli M. Angiogenesis and hypertension: the dual role of anti-hypertensive and anti-angiogenic therapies. Curr Vasc Pharmacol. 2012; 10(4): 479–93.
  16. Leychenko A., Konorev E., Jijiwa M., Matter M.. Stretch-Induced Hypertrophy Activates NFkB-Mediated VEGF Secretion in Adult Cardiomyocytes. PLoS ONE. 2011 Dec 13: 6. PMID: 22174951. PMCID: PMC3236775.
  17. Li J, Hampton T, Morgan J P, Simons M. Stretch-induced VEGF expression in the heart. J Clin Invest. 1997 Jul 1; 100(1): 18–24. PMID: 9202052. PMCID: PMC508160.
  18. Zheng W, Seftor EA, Meininger CJ, Hendrix MJ, Tomanek RJ. Mechanisms of coronary angiogenesis in response to stretch: role of VEGF and TGF-beta. Am J Physiol Heart Circ Physiol. 2001 Feb; 280(2): H909-17. PMID:11158993.
  19. Wojakowski W, Maslankiewicz K, Ochala A, Wyderka R, Zuk-Popiolek I, Flak Z, et al. The pro- and anti-inflammatory markers in patients with acute myocardial infarction and chronic stable angina. Int J Mol Med. 2004 Aug; 14(2): 317-22. PMID: 15254785.
  20. Lacchini R, Luizon MR, Gasparini S, Ferreira-Sae MS, Schreiber R, Nadruz W, et al. Effect of Genetic Polymorphisms of Vascular Endothelial Growth Factor on Left Ventricular Hypertrophy in Patients With Systemic Hypertension. Am J Cardiol. 2014; 113: 491e496. PMID: 24321896.
  21. Han X, Liu L, Niu J, Yang J, Zhang Z. Association between VEGF polymorphisms (936c/t, -460t/c and -634g/c) with haplotypes and coronary heart disease susceptibility. Int J Clin Exp Pathol. 2015; 8(1): 922-7.
  22. Li L, Pan Y, Zhang D. Association of Genetic Polymorphisms on Vascular Endothelial Growth Factor and its Receptor Genes with Susceptibility to Coronary Heart Disease. Med Sci Monit. 2016; 22: 31–40. PMID: 26726843. PMCID: PMC4706102.
  23. Nia SK, Ziaee S, Boroumand MA, Anvari MS, Pourgholi L, Jalali A. The impact of vascular endothelial growth factor +405 C/G polymorphism on long-term outcome and severity of coronary artery disease. Journal of Clinical Laboratory Analysis. 2017; 31(4): e22066. PMID: 27704620.
  24. Douvaras P, Antonatos DG, Kekou K, Patsilinakos S, Chouliaras G, Christou A, et al. Association of VEGF gene polymorphisms with the development of heart failure in patients after myocardial infarction. Cardiology. 2009; 114(1): 11-8. PMID: 19332989.