Association of vascular endothelial growth factor B (VEGFВ) gene polymorphisms with intracranial aneurysms
https://doi.org/10.18699/VJ18.442
Abstract
Intracranial aneurysm (IA) is a complex disease resulting in subarachnoid hemorrhage (SAH) due to a rupture. The average worldwide prevalence of this disease is about 2–5 %, with 50 % of them ending in death or neurological disorders of varying severity, with a high probability of recurrence of hemorrhage during the frst half of the year after rupture. Subarachnoid hemorrhage is annually registered in at least 18 thousand people in Russia. Associations of polymorphic variants rs594942 and rs11603042 of the VEGFB gene in intracranial aneurysm development in the Volga-Ural region of the Russian Federation with the presence of the symptom complex of undifferentiated connective tissue dysplasia (uDST) and arterial hypertension (AH) were investigated. The C* allele rs594942 and rs11603042 of the VEGFB gene is a marker of an increased risk of IA as a whole (p = 0.025; χ2 = 5.052; OR = 1.32) in women as a whole (p = 0.001; χ2 = 10.124; OR = 1.70) and in comorbid state with uDCT (p = 0.002; χ2 = 9.501; OR = 2.34) and AG (p = 0.006; χ2 = 7.385; OR = 2.109). We found that the genotype *C*C of locus rs594942 of the VEGFB gene is a marker of an increased risk of intracranial aneurysm in general (p = 0.017; χ2 = 5.702; OR = 1.49) and among women in general (p = 0.0005; χ2 = 12.078; OR = 2.25) and with the symptomatic complex uCTD (p = 0.007; χ2 = 7.173; OR = 2.67) and AH (p = 0.010; χ2 = 6.471; OR = 2.51). We have obtained new results on the role of polymorphic variants of the VEGFB gene in the formation of intracranial aneurysm, taking into account the presence of the symptom complex uDCT and AH among the residents of the Volga-Ural region of Russia. A burdened comorbid background and the presence of undifferentiated connective tissue dysplasia and arterial hypertension can contribute to an increased risk of intracranial aneurysm, as evidenced by the results of our study.
About the Authors
R. I. SultanovaRussian Federation
Ufa
R. I. Khusainova
Russian Federation
Ufa
E. R. Lebedeva
Russian Federation
Ekaterinburg
M. A. Yankina
Russian Federation
Ufa
D. V. Gilev
Russian Federation
Ekaterinburg
E. K. Khusnutdinova
Russian Federation
Ufa
References
1. Krylov V.V., Prirodov A.V., Petrikov S.S. Nontraumatic subarachnoid hemorrhage: diagnosis and treatment. Nevrologiya i Revmatologiya = Neurology and Rheumatology. 2008;1:14-18. (in Russian)
2. Skorokhod A.A., Brichkovskaya T.V. Arterial aneurysms of the brain: etiology and pathogenesis. Meditsinskiy Zhurnal (Minsk) = Medical Journal (Minsk). 2007;3:4-7. (in Russian)
3. Yakovlev V.M., Nechaeva G.I. Systemic connective tissue dysplasia: the urgency of the problem in the internal disease clinic. Sibirskiy Meditsinskiy Zhurnal = Siberian Medical Journal. 2011;3:9-12. (in Russian)
4. Behrouz R., Birnbaum L., Grandhi R., Johnson J., Misra V., Palacio S., Seif A., Topel C., Garvin R., Caron J.L. Cannabis use and outcomes in patients with aneurysmal subarachnoid hemorrhage. Stroke. 2016; 47(5):1371-1373. DOI 10.1161.
5. Cai W., Hu C., Gong J., Lan Q. Anterior communicating artery aneurysm morphology and the risk of rupture. World Neurosurg. 2018; 109:119-126. DOI 10.1016.
6. Dority J.S., Oldham J.S. Subarachnoid hemorrhage: an update. Anesthesiol. Clin. 2016;34(3):577-600. DOI 10.1016.
7. Edwards D.R., Romero R., Kusanovic J.P., Hassan S.S., Mazaki-Tovi S., Vaisbuch E., Kim C.J., Erez O., Chaiworapongsa T., Pearce B.D., Bartlett J., Friel L.A., Salisbury B.A., Anant M.K., Vovis G.F., Lee M.S., Gomez R., Behnke E., Oyarzun E., Tromp G., Menon R., Williams S.M. Polymorphisms in maternal and fetal genes encoding for proteins involved in extracellular matrix metabolism alter the risk for small-for-gestational-age. J. Matern. Fetal Neonatal. Med. 2011;24(2):362-380. DOI 10.3109/14767058.
8. Ferrara N. VEGF-A: a critical regulator of blood vessel growth. Eur. Cytokine Netw. 2009;20(4):158-163. DOI 10.1684/ecn.
9. Grant R.A., Cord B.J., Kuzomunhu L., Gilmore E., Matouk C.C. Aneurysmal subarachnoid hemorrhage and severe, catheter-induced vasospasm associated with excessive consumption of a caffeinated energy drink. Interv. Neuroradiol. 2016;22(6):674-678.
10. Guo S., Colbert L.S., Fuller M., Zhang Y., Gonzalez-Perez R.R. Vascular endothelial growth factor receptor-2 in breast cancer. Biochim. Biophys. Acta. 2010;1806(1):108-121. DOI 10.1016/j.bbcan.
11. Lambrechts D., Thienpont B., Thuillier V., Sagaert X., Moisse M., Peuteman G., Pericay C., Folprecht G., Zalcberg J., Zilocchi C., Margherini E., Chiron M., Van Cutsem E. Evaluation of effcacy and safety markers in a phase II study of metastatic colorectal cancer treated with aflibercept in the frst-line setting. Br. J. Cancer. 2015; 113(7):1027-1034. DOI 10.1038/bjc.2015.329.
12. Lebedeva E.R., Sakovich V.P. Systemic connective tissue abnormalities in patients with saccular intracranial aneurysms. Acta Neurol. Scand. 2013;128:130-135.
13. Liu P., Zhou Y., An Q., Song Y., Chen X., Yang G.Y., Zhu W. Erythropoietin stimulates endothelial progenitor cells to induce endothelialization in an aneurysm neck after coil embolization by modulating vascular endothelial growth factor. Stem Cells Transl. Med. 2016; 5(9):1182-1189.
14. Losordo D.W., Diommeler S. Therapeutic angiogenesis and vasculogenesis for ischemic disease. Part 1: angiogenic cytokines. Circulation. 2004;109:2487-2491.
15. Mathew C.C. The isolation of high molecular weight eukaryotic DNA. Methods Mol. Biol. 1985;2:31-34. DOI 10.1385/0-89603-064-4:31.
16. Mosca M., Tani C., Carli L., Bombardieri S. Undifferentiated CTD: a wide spectrum of autoimmune diseases. Best Pract. Res. Clin. Rheumatol. 2012;26:73-77. DOI 10.1016/j.berh.
17. Mosca M., Tani C., Vagnani S., Carli L., Bombardieri S. The diagnosis and classifcation of undifferentiated connective tissue diseases. J. Autoimmun. 2014;48-49:50-52. DOI 10.1016/j.jaut.
18. Ostergaard J.R., Oxlund H. Collagen type III defciency in patients with rupture of intracranial saccular aneurysms. J. Neurosurg. 1987; 67:690-696.
19. Peters D.G., Kassam A.B., Feingold E., Heidrich-O’Hare E., Yonas H., Ferrell R.E., Brufsky A. Molecular anatomy of an intracranial aneurysm: Coordinated expression of genes involved in wound healing and tissue remodeling. Stroke. 2001;32:1036-1042.
20. Prockop D.J., Kivirikko K.I. Collagens: molecular biology, diseases, and potentials for therapy. Annu. Rev. Biochem. 1995;64:403-434
21. Qian Z., Kang H., Jiang C., Tang K., Jiang C., Wu Z., Li Y., Liu A. Assessment of risk of aneurysmal rupture in patients with normotensives, controlled hypertension, and uncontrolled hypertension. J. Stroke Cerebrovasc. Dis. 2016;25(7):1746-1752.
22. Qureshi A.I., Suri M.F., Yahia A.M., Suarez J.I., Guterman L.R., Hopkins L.N., Tamargo R.J. Risk factors for subarachnoid hemorrhage. Neurosurgery. 2001;49:607-612.
23. Schievink W.I. Marfan syndrome and intracranial aneurysms. Stroke. 1999;30:2767-2768.
24. Sudhesan A., Rajappa M., Chandrashekar L. Vascular endothelial growth factor (VEGF) gene polymorphisms (rs699947, rs833061, and rs2010963) and psoriatic risk in south indian tamils. Hum. Immunol. 2017;78(10):657-663. DOI 10.1016/j.humimm.2017.08.004.
25. Tromp G., Weinsheimer S., Ronkainen A., Kuivaniemi H. Molecular basis and genetic predisposition to intracranial aneurysm. Ann. Med. 2014;46(8):597-606. DOI 10.3109/07853890.2014.949299.
26. Xu M., Zhang Y., Tang L., Huang H. Concentration analysis of hypoxiinducible factor-1α; and vascular endothelial growth factor in patients with aortic aneurysm at different stages and its clinical signifcance. Cell Mol. Biol. (Noisy-le-Grand). 2016;62(1):73-76.
27. Wolanska M., Bankowska-Guszczyn E., Sobolewski K., Kowalewski R. Expression of VEGFs and its receptors in abdominal aortic aneurysm. Int. Angiol. 2015;34(6):520-528.
28. Zhang J., Claterbuck R.E. Molecular genetics of human intracranial aneurysms. Int. J. Stroke. 2008;3(4):272-287. DOI 10.1111/j.1747-4949.