Is there an Association Between-2549 Insertion/Deletion Polymorphisms in the Promotor Region of the Gene Encoding for VEGFA as a Risk Factor and the Idiopathic Recurrent Spontaneous Miscarriage in a Sample of Jordanian Women? View PDF

^*Omar A Azzam
Department Of Obstetrics And Gynecology, Faculty Of Medicine, Mutah University, Jordan

^*Corresponding Author:

Omar A Azzam
Department Of Obstetrics And Gynecology, Faculty Of Medicine, Mutah University, Jordan
Email:oabuazzam@yahoo.com

Published on: 2020-03-04

Abstract

Background: At least 50% of the cases of recurrent spontaneous miscarriage is aetiologically idiopathic. Recently various genetic polymorphisms have been proposed as susceptibility risk factors for pregnancy loss.
Objective: The aim of the present case control-study is to establish the association between the functional -2549 I/D polymorphisms in the promoter region of the vascular endothelial growth factor A (VEGFA) gene and idiopathic recurrent spontaneous miscarriage (IRSM) in a sample of Jordanian women.
Subjects and Methods: 328 subjects were recruited, 103 and 98 women with primary and secondary IRSM, respectively, 127 normal women were selected as a control group. Genomic DNA was isolated from a blood sample withdrawn from each participant, then, -2549 I/D polymorphisms of the VEGFA gene were genotyped by Polymerase Chain Reaction (PCR).
Results: The obtained results revealed that ID polymorphism and D allele of VEGFA -2549 I/D polymorphisms have the highest frequencies in both primary and secondary IRSM patients, no significant difference between the three groups regarding polymorphisms and allele frequencies, patients with DD+ID genetic models have positive association with high risk of IRSM versus II model, and patients with D allele are more liable to have IRSM than those having I allele, no significant difference in the association of VEGFA -2549 I/D polymorphisms with IRSM in the three genetic models of the primary and secondary IRSM patients.
Conclusion: patients with ID genetic model of -2549 I/D polymorphisms in the VEGFA gene’s promoter region and D allele have a higher risk for IRSM.

Keywords

Polymorphisms; Miscarriage; VEGFA; Idiopathic; Insertion/Deletion; Recurrent spontaneous miscarriage are aetiologically idiopathic; PCR

Introduction

IRSM, the frequent obstetric complication, can be explained as a loss of three or more successive pregnancy prior to the 20th weeks of gestation. Up to 50% of IRSM patients have unknown underlying etiology and it affects 1-5% of the women who are seeking bear children [1]. Different factors like endocrine dysfunctions, autoimmune diseases, and uterine pathologies in addition to environmental and nutritional factors have been demonstrated for their direct and/or indirect effects on miscarriage [2]. Placental circulation in addition to fetal vasculature should be sufficient for maintaining normal pregnancy which is requiring angiogenesis. Such a process is dependent upon multiple factors, including VEGFA [3].
VEGFA, the potent angiogenic factor, is secreted by both fetal and maternal trophoblastic cells for enhancing vascular permeability, hematopoiesis, endothelial cell proliferation and survival [4]. VEGF has receptors (VEGFR1/Flt-1, VEGFR2/KDR/Flk-1) [5], its functions are related to human reproduction, including placental organization and fetal angiogenesis, in addition to pre-decidualization and gametogenesis [6]. The rate of expression of VEGFA/VEGFR was the highest in the maternal side of the placenta [7], which is different under conditions of normal pregnancy versus the complicated one. This is because of the abnormalities of angiogenesis during implantation and placenta formation early in pregnancy which may lead to IRSM [3].