Association between the estrogen receptor α gene polymorphisms rs2234693 and rs9340799 and severe and mild pre-eclampsia: a meta-analysis

Biosci Rep. 2019 Feb 8;39(2):BSR20181548. doi: 10.1042/BSR20181548. Print 2019 Feb 28.


This meta-analysis was performed in order to determine the associations between the estrogen receptor α (ESR1) gene PvuII site (-397T/C, rs2234693) and XbaI site (-351A/G, rs9340799) polymorphisms with severe and mild pre-eclampsia. Eligible studies were identified by searching PubMed, Medline, Embase, China National Knowledge Infrastructure (CNKI), and WanFang databases until May 2018. The pooled odds ratio (OR) and 95% confidence interval (CI) were used to calculate the associations. Six articles (consisting of seven studies; one article was considered as two separate studies with two different subpopulations) investigated the ESR1 gene PvuII -397T/C and XbaI -351A/G polymorphisms in severe and mild pre-eclampsia patients and included controls. The pooled results indicated an increased risk of severe pre-eclampsia for the XbaI -351A/G polymorphism (OR = 1.67, 95% CI = 1.10-2.25, P=0.017 for GG compared with AA+GA; OR = 1.81, 95% CI = 1.17-2.82, P=0.008 for GG compared with GA). The GG genotype of the ESR1 XbaI polymorphism could be a genetic risk factor for severe pre-eclampsia susceptibility. However, the ESR1 gene PvuII -397T/C polymorphism was not significantly associated with the risk of severe pre-eclampsia, and there was no association between mild pre-eclampsia and the ESR1 gene PvuII -397T/C and XbaI -351A/G polymorphisms separately. The current meta-analysis indicates that the ESR1 XbaI genetic polymorphism may be associated with severe pre-eclampsia. However, there was no association of the ESR1 gene PvuII and XbaI polymorphisms with the risk of mild pre-eclampsia. Owing to the low statistical power, the results may not be sufficiently robust and this conclusion should be interpreted cautiously, which highlights the requirement for large-scale and high-quality studies in this field.

Keywords: estrogen receptor alpha; meta-analysis; polymorphisms; preeclampsia.

Publication types

  • Meta-Analysis

MeSH terms

  • DNA-Cytosine Methylases / genetics
  • Deoxyribonucleases, Type II Site-Specific / genetics
  • Estrogen Receptor alpha / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Polymorphism, Single Nucleotide*
  • Pre-Eclampsia / genetics*
  • Pregnancy


  • ESR1 protein, human
  • Estrogen Receptor alpha
  • DNA modification methylase PvuII
  • DNA-Cytosine Methylases
  • endodeoxyribonuclease XBAI
  • Deoxyribonucleases, Type II Site-Specific