Download PDF
Thromb Haemost 2022; 122(03): 363-376
DOI: 10.1055/a-1518-1756
Endothelium and Angiogenesis

Association of VEGF and p53 Polymorphisms and Spiral Artery Remodeling in Recurrent Pregnancy Loss: A Systematic Review and Meta-Analysis

Tamil Mani Subi
1   Division of Blood and Vascular Biology, Department of Life Sciences, School of Life Sciences, Central University of Tamil Nadu, Thiruvarur, India
,
Vinodhini Krishnakumar
1   Division of Blood and Vascular Biology, Department of Life Sciences, School of Life Sciences, Central University of Tamil Nadu, Thiruvarur, India
,
Chandreswara Raju Kataru
1   Division of Blood and Vascular Biology, Department of Life Sciences, School of Life Sciences, Central University of Tamil Nadu, Thiruvarur, India
,
Inusha Panigrahi
2   Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India
,
Meganathan Kannan 
1   Division of Blood and Vascular Biology, Department of Life Sciences, School of Life Sciences, Central University of Tamil Nadu, Thiruvarur, India
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Abstract

Many studies have reported the association of VEGF-1154G/A, VEGF 936C/T, and p53 Arg72Pro polymorphisms with recurrent pregnancy loss (RPL), but the outcomes are inconsistent. We have used a meta-analysis to associate these polymorphisms with RPL, having the spiral artery remodeling as a major risk factor. The studies were identified from three different reputed databases, namely ScienceDirect, PubMed/Medline, and Scopus. The eligible studies of VEGF-1154G/A, VEGF 936C/T, and p53Arg72Pro polymorphisms associated with the RPL were selected for the analysis. They were segregated into three different ethnic groups as Asians, Caucasians, and mixed population. For the analysis, the overall prevalence, odds ratio, risk ratio, relative risk ratio, and p-values were calculated. A total of 3,241 RPL cases and 3,205 healthy controls from 21 different case–control studies were analyzed. RPL was highly prevalent in the mixed population with VEGF-1154G/A and p53 Arg72Pro polymorphisms (70.04 and 66.46%, respectively) and in the Asian population with VEGF 936C/T polymorphism (53.58%). The homozygous recessive genotypes of VEGF and p53 exhibited significant association between the respective polymorphisms and RPL along with the increased risk of outcome. The current analysis conclusively reports the geographic distribution of the different genetic polymorphisms which shows high association with the progression of RPL. Understanding the spectrum of polymorphisms on different populations with the spiral artery remodeling as a risk factor encloses the importance of the vasculature during the pregnancy.

Keywords

association - p53 - VEGF - polymorphisms - RPL

Supplementary Material



Publication History

Received: 03 January 2021

Accepted: 24 May 2021

Accepted Manuscript online:
26 May 2021

Article published online:
04 July 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Zhu Y, Lu H, Huo Z. et al. MicroRNA-16 inhibits feto-maternal angiogenesis and causes recurrent spontaneous abortion by targeting vascular endothelial growth factor. Sci Rep 2016; 6 (April): 35536
    CrossrefPubMedGoogle Scholar
  • 2 Pijnenborg R, Vercruysse L, Hanssens M. The uterine spiral arteries in human pregnancy: facts and controversies. Placenta 2006; 27 (9–10): 939-958
    CrossrefPubMedGoogle Scholar
  • 3 Whitley GSJ, Cartwright JE. Trophoblast-mediated spiral artery remodelling: a role for apoptosis. J Anat 2009; 215 (01) 21-26
    CrossrefPubMedGoogle Scholar
  • 4 Salomon C, Yee SW, Mitchell MD, Rice GE. The possible role of extravillous trophoblast-Derived exosomes on the uterine spiral arterial remodeling under both normal and pathological conditions. Biomed Res Int 2014; 2014: 693157
    CrossrefPubMedGoogle Scholar
  • 5 Burton GJ, Woods AW, Jauniaux E, Kingdom JCP. Rheological and physiological consequences of conversion of the maternal spiral arteries for uteroplacental blood flow during human pregnancy. Placenta 2009; 30 (06) 473-482
    CrossrefPubMedGoogle Scholar
  • 6 Whitley GSJ, Cartwright JE. Cellular and molecular regulation of spiral artery remodelling: lessons from the cardiovascular field. Placenta 2010; 31 (06) 465-474
    CrossrefPubMedGoogle Scholar
  • 7 Robson A, Lash GE, Innes BA, Zhang JY, Robson SC, Bulmer JN. Uterine spiral artery muscle dedifferentiation. Hum Reprod 2019; 34 (08) 1428-1438
    CrossrefPubMedGoogle Scholar
  • 8 Eddy AC, Bidwell III GL, George EM. Pro-angiogenic therapeutics for preeclampsia. Biol Sex Differ 2018; 9 (01) 36
    CrossrefPubMedGoogle Scholar
  • 9 Cerdeira AS, Karumanchi SA. Angiogenic factors in preeclampsia and related disorders. Cold Spring Harb Perspect Med 2012; 2 (11) 1-17
    CrossrefPubMedGoogle Scholar
  • 10 Fraga LR, Dutra CG, Boquett JA. et al. p53 signaling pathway polymorphisms associated to recurrent pregnancy loss. Mol Biol Rep 2014; 41 (03) 1871-1877
    CrossrefPubMedGoogle Scholar
  • 11 Winship A, Correia J, Zhang JG, Nicola NA, Dimitriadis E. Leukemia inhibitory factor (LIF) inhibition during mid-gestation impairs trophoblast invasion and spiral artery remodelling during pregnancy in mice. PLoS One 2015; 10 (10) e0129110
    CrossrefPubMedGoogle Scholar
  • 12 Tapia A, Salamonsen LA, Manuelpillai U, Dimitriadis E. Leukemia inhibitory factor promotes human first trimester extravillous trophoblast adhesion to extracellular matrix and secretion of tissue inhibitor of metalloproteinases-1 and -2. Hum Reprod 2008; 23 (08) 1724-1732
    CrossrefPubMedGoogle Scholar
  • 13 Papazoglou D, Galazios G, Papatheodorou K. et al. Vascular endothelial growth factor gene polymorphisms and idiopathic recurrent pregnancy loss. Fertil Steril 2005; 83 (04) 959-963
    CrossrefPubMedGoogle Scholar
  • 14 Aggarwal S, Parveen F, Faridi RM, Phadke S, Borkar M, Agrawal S. Vascular endothelial growth factor gene polymorphisms in North Indian patients with recurrent miscarriages. Reprod Biomed Online 2011; 22 (01) 59-64
    CrossrefPubMedGoogle Scholar
  • 15 Almawi WY, Saldanha FL, Mahmood NA, Al-Zaman I, Sater MS, Mustafa FE. Relationship between VEGFA polymorphisms and serum VEGF protein levels and recurrent spontaneous miscarriage. Hum Reprod 2013; 28 (10) 2628-2635
    CrossrefPubMedGoogle Scholar
  • 16 Coulam CB, Jeyendran RS. Vascular endothelial growth factor gene polymorphisms and recurrent pregnancy loss. Am J Reprod Immunol 2008; 59 (04) 301-305
    CrossrefPubMedGoogle Scholar
  • 17 Eller AG, Branch DW, Nelson L, Porter TF, Silver RM. Vascular endothelial growth factor-A gene polymorphisms in women with recurrent pregnancy loss. J Reprod Immunol 2011; 88 (01) 48-52
    CrossrefPubMedGoogle Scholar
  • 18 Lee HH, Hong SH, Shin SJ, Ko JJ, Oh D, Kim NK. Association study of vascular endothelial growth factor polymorphisms with the risk of recurrent spontaneous abortion. Fertil Steril 2010; 93 (04) 1244-1247
    CrossrefPubMedGoogle Scholar
  • 19 Li L, Donghong L, Shuguang W, Hongbo Z, Jing Z, Shengbin L. Polymorphisms in the vascular endothelial growth factor gene associated with recurrent spontaneous miscarriage. J Matern Fetal Neonatal Med 2013; 26 (07) 686-690
    CrossrefPubMedGoogle Scholar
  • 20 Magdoud K, Dendana M, Herbepin V. et al. Identification of specific vascular endothelial growth factor susceptible and protective haplotypes associated with recurrent spontaneous miscarriages. Hum Reprod 2012; 27 (05) 1536-1541
    CrossrefPubMedGoogle Scholar
  • 21 Samli H, Demir BÇ, Ozgöz A, Atalay MA, Uncu G. Vascular endothelial growth factor gene 1154 G/A, 2578 C/A, 460 C/T, 936 C/T polymorphisms and association with recurrent pregnancy losses. Genet Mol Res 2012; 11 (04) 4739-4745
    CrossrefPubMedGoogle Scholar
  • 22 Su MT, Lin SH, Lee IW, Chen YC, Kuo PL. Association of polymorphisms/haplotypes of the genes encoding vascular endothelial growth factor and its KDR receptor with recurrent pregnancy loss. Hum Reprod 2011; 26 (04) 758-764
    CrossrefPubMedGoogle Scholar
  • 23 Traina E, Daher S, Moron AF, Sun SY, Franchim CS, Mattar R. Polymorphisms in VEGF, progesterone receptor and IL-1 receptor genes in women with recurrent spontaneous abortion. J Reprod Immunol 2011; 88 (01) 53-57
    CrossrefPubMedGoogle Scholar
  • 24 Vidyadhari M, Sujatha M, Krupa P, Nallari P, Venkateshwari A. Association of genetic polymorphism of vascular endothelial growth factor in the etiology of recurrent pregnancy loss: a triad study. J Assist Reprod Genet 2019; 36 (05) 979-988
    CrossrefPubMedGoogle Scholar
  • 25 Xing X, Yan J, Zhao Y, You L, Bian Y, Chen ZJ. Association of vascular endothelial growth factor gene polymorphisms with recurrent spontaneous abortion in Chinese Han women. Am J Reprod Immunol 2011; 65 (05) 521-525
    CrossrefPubMedGoogle Scholar
  • 26 Pietrowski D, Bettendorf H, Riener EK. et al. Recurrent pregnancy failure is associated with a polymorphism in the p53 tumour suppressor gene. Hum Reprod 2005; 20 (04) 848-851
    CrossrefPubMedGoogle Scholar
  • 27 Coulam CB, Kay C, Jeyendran RS. Role of p53 codon 72 polymorphism in recurrent pregnancy loss. Reprod Biomed Online 2006; 12 (03) 378-382
    CrossrefPubMedGoogle Scholar
  • 28 Firouzabadi RD, Ghasemi N, Rozbahani MA, Tabibnejad N. Association of p53 polymorphism with ICSI/IVF failure and recurrent pregnancy loss. Aust N Z J Obstet Gynaecol 2009; 49 (02) 216-219
    CrossrefPubMedGoogle Scholar
  • 29 Kaare M, Bützow R, Ulander VM, Kaaja R, Aittomäki K, Painter JN. Study of p53 gene mutations and placental expression in recurrent miscarriage cases. Reprod Biomed Online 2009; 18 (03) 430-435
    CrossrefPubMedGoogle Scholar
  • 30 Fang Y, Kong B, Yang Q, Ma D, Qu X. The p53-HDM2 gene-gene polymorphism interaction is associated with the development of missed abortion. Hum Reprod 2011; 26 (05) 1252-1258
    CrossrefPubMedGoogle Scholar
  • 31 Lledo B, Turienzo A, Ortiz JA. et al. Negative effect of P72 polymorphism on p53 gene in IVF outcome in patients with repeated implantation failure and pregnancy loss. J Assist Reprod Genet 2014; 31 (02) 169-172
    CrossrefPubMedGoogle Scholar
  • 32 Yoon SH, Choi YM, Kim JJ. et al. No association of p53 codon 72 polymorphism with idiopathic recurrent pregnancy loss in Korean population. Eur J Obstet Gynecol Reprod Biol 2015; 192: 6-9
    CrossrefPubMedGoogle Scholar
  • 33 Hazard AQ. A racialized deconstruction? Ashley Montagu and the 1950 UNESCO Statement on Race. Transforming Anthropol 2011; 19 (02) 174-186
    CrossrefPubMedGoogle Scholar