Abstract
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.
Highlights
Received: 06 September 2018Revised: 28 December 2018Accepted: 09 January 2019Accepted Manuscript Online: Version of Record published: Pre-eclampsia is a major leading cause of maternal mortality worldwide (2–5%), affecting women after weeks of pregnancy, and is characterized by increased systemic vascular resistance, decreased blood volume, vascular endothelial cell destruction, and renal hemodynamic abnormalities [1]
Of these seven studies: seven studies assessed the association between the ESR1 -397T/C PvuII polymorphism and severe pre-eclampsia susceptibility, five studies assessed the ESR1 -397T/C PvuII polymorphism and mild pre-eclampsia susceptibility, four studies assessed the ESR1 -351A/G XbaI polymorphism and severe pre-eclampsia susceptibility, and three studies assessed the ESR1 -351A/G XbaI polymorphism and mild pre-eclampsia susceptibility
Our findings show that before excluding the two studies that deviated from Hardy–Weinberg equilibrium (HWE) [12,14], the GG genotype increased the risk of severe pre-eclampsia
Summary
Accepted Manuscript Online: Version of Record published: Pre-eclampsia is a major leading cause of maternal mortality worldwide (2–5%), affecting women after weeks of pregnancy, and is characterized by increased systemic vascular resistance, decreased blood volume, vascular endothelial cell destruction, and renal hemodynamic abnormalities [1]. Approximately 40000 maternity patients could die due to pre-eclampsia and eclampsia resulting from a shallow implanted placenta, leading to severe immune reaction involved with inflammatory mediators of the placenta, and acting on the vascular endothelium [1]. The estrogen receptor α (ESR1) gene is located on the long arm of chromosome 6 (6q25.1) and contains eight exons [3]. ESR1 is a ligand-activated transcription factor that can be activated by growth factors in the License 4.0 (CC BY)
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