Implication of VEGFR2 in endometriosis: A structural biological and genetic approach

Matalliotaki,Charoula; Eliopoulos,Elias; Matalliotakis,Michail; Kalogiannidis,Ioannis; Matalliotakis,Ioannis; Spandidos,Demetrios   A.; Goulielmos,George   N.; Zervou,Maria   I.

doi:10.3892/wasj.2019.29

Implication of VEGFR2 in endometriosis: A structural biological and genetic approach

Authors:
- Charoula Matalliotaki
- Elias Eliopoulos
- Michail Matalliotakis
- Ioannis Kalogiannidis
- Ioannis Matalliotakis
- Demetrios A. Spandidos
- George N. Goulielmos
- Maria I. Zervou
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Affiliations: Section of Molecular Pathology and Human Genetics, Department of Internal Medicine, School of Medicine, University of Crete, 71003 Heraklion, Greece, Laboratory of Genetics, Department of Biotechnology, Agricultural University of Athens, 11855 Athens, Greece, Third Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece, Department of Obstetrics and Gynecology, Venizeleio and Pananio General Hospital of Heraklion, 71409 Heraklion, Greece, Laboratory of Clinical Virology, School of Medicine, University of Crete, 71003 Heraklion, Greece
Published online on: December 3, 2019 https://doi.org/10.3892/wasj.2019.29
Pages: 283-289
Copyright: © Matalliotaki et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Vascular endothelial growth factor receptor 2 (VEGFR2) is a tyrosine kinase receptor, which exerts its activity by binding to VEGF, a major mediator of angiogenesis. Endometriosis is one of the most common gynecological diseases in women of reproductive age, characterized mainly by pelvic pain and infertility. Among the various hypotheses that have been suggested thus far for the development of this condition, it is considered that it is closely related to angiogenic responses. Polymorphisms of the VEGFR2 gene have already been shown to be associated with vascular diseases, such as coronary heart disease (CHD). In the present study, the authors sought to clarify the structural/functional consequences of rs2305948, a common single nucleotide polymorphism (SNP) of VEGFR2 in endometriosis and to investigate the association of this SNP with susceptibility to endometriosis, probably by influencing endothelial cells. This study comprised 162 patients with endometriosis (stages I‑IV) hospitalized for endometriosis, diagnosed by laparoscopic intervention and histologically confirmed, and 170 women in the control group from a genetic homogeneous population. Genotyping of the V297I (rs2305948) polymorphism was performed through TaqMan technology. Three‑dimensional (3D) homology modelling was applied for the localization of the polymorphism under study on the VEGFR2 protein. Modelling revealed that the V297I polymorphism may affect the efficiency of trans‑autophosphorylation and cell signaling. The results of statistical analysis revealed that there was no significant allelic and genotypic association of the rs2305948 SNP between the disease (stages I‑IV) and the control group. Further analysis did not reveal any association of this SNP with an increased susceptibility to endometriosis for stages I and II or III and IV of the disease only. Apart from structural data that suggest that the rs2305948 SNP of VEGFR2 gene may contribute to the pathogenesis of endometriosis by impairing VEGF signaling and increasing angiogenesis, in the present study, this SNP was not found to be associated with an increased susceptibility to endometriosis.

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