Association of -460C/T and +405 G/C polymorphisms of vascular endothelial growth factor gene and susceptibility of ovarian hyperstimulation syndrome

Abstract

Background:Ovarian hyperstimulation syndrome (OHSS) is one of the most important complications of assisted reproduction treatment. Many substances are involved in the regulation of the vascular permeability, which have been concerned to cause OHSS. Vascular endothelial growth factor (VEGF) has emerged as one of the main angiogenic factors, which could be responsible for increased vascular permeability.Objective: In this study the association of vascular endothelial growth factor -460C/T and +405 G/C polymorphisms and susceptibility to ovarian hyperstimulation syndrome was evaluated. Materials and Methods:In this cross sectional study, VEGF gene polymorphisms were amplified by Polymerase chain reaction- Restriction Fragment Length Polymorphism in 75 women with established OHSS (case group) and 85 normoresponder (control group) which received conventional ovarian stimulation regimen. Results:There was no significant difference in the frequency of -460 C/T polymorphism between cases and controls (p=0.85). The frequency of +405 G/C polymorphism was significantly higher in the OHSS women (p=0.03, OR=2.44; 95% CI=1.23-4.82). Conclusion: In women who developed OHSS, VEGF gene polymorphism +405 could be effective. Two of the polymorphisms -460 C/T and +405 G/C were reported to be associated with increased VEGF basal promoter activity. However, only +405 G/C gene polymorphisms were more frequent in cases than controls.

ANG II, VEGF in Ovarian Hyperstimulation Syndrome

“…If the implication of VEGF in the development of OHSS is indisputable, the part this factor is playing in triggering these severe forms is less clear. In this context, many studies have indicated that the development of severe forms of disease requires the implication of adjuvant factors, such as certain VEGF (19) or VEGF receptor polymorphisms (VEGFR1-519 and VEGF-405) (20), cytokines (interleukin (IL) 2, IL6, IL8) or cytokine signaling (SOCS) proteins (21) and, last but not least, certain factors involved in angiogenesis (Pigment Epithelium-Derived Factor) (PEDF) (22). This is also the case of severe OHSS forms occurring in patients undergoing VEGF receptor blockers therapy.…”

Factor de crecimiento endotelial vascular durante la foliculogénesis en el ovario humano.

“…Se han demostrado altas concentraciones de VEGF en líquido ascítico de pacientes con síndrome de hiperestimulación ovárica (27) y varios estudios han demostrado concentraciones elevadas de VEGF en el suero y el líquido folicular de mujeres con síndrome de hiperestimulación ovárica (28)(29)(30) . Tanto el líquido folicular como peritoneal de pacientes con alta respuesta a hiperestimulación ovárica controlada muestran aumento significativo en la tasa de permeabilidad a través de células endoteliales in vitro (31) .…”

Rare genetic variants suggest dysregulation of signaling pathways in low- and high-risk patients developing severe ovarian hyperstimulation syndrome

“…To investigate if rare variants potentially involved in the development of OHSS were present, variants called in the 12 cases with OHSS were filtered using a predefined in silico gene panel including 76 genes predisposing to OHSS (Online Resource 2). The genes included in the gene panel were selected based on an extensive literature search in PubMed and Online Mendelian Inheritance in Man (OMIM) and were implicated in controlled ovarian stimulation response, associated with OHSS or regulation of gonadotropin action and/or ovarian angiogenesis [3,14,[16][17][18][19][20][21][22][23][24]. The gene panel included both known disease-associated genes related to OHSS and candidate genes which association with OHSS needs further study.…”