Polymorphisms and Plasma Level of Transforming Growth Factor-Beta 1 and Risk for Preeclampsia: A Systematic Review

Abstract

BackgroundTransforming growth factor-beta 1 (TGF-β1) is thought to be involved in the pathogenesis of preeclampsia (PE), but the results are inconsistent among studies. This article aims to compile an overview of the studies about the associations of TGF-β 1 polymorphism and plasma level with PE risk and to provide recommendations for future research.Methods and ResultsThe databases PubMed, Embase and Web of Science were searched up to December 2013. Five studies investigating the associations of four polymorphisms with the risks of PE were involved. A meta-analysis was conducted for the 869T>C polymorphism and PE risk. The results show that genotype TT of 869T>C polymorphism is a protective factor of PE (pooled odds ratio = 0.73, 95% CI: 0.56, 0.95). Eight case-control studies reported the plasma level of TGF-β 1. The substantial heterogeneity among studies may be attributed to the differences in the blood sample processing and the TGF-β 1 analysis kits. The results suggest that plasma TGF-β 1 level in the second trimester was significantly lower in the PE group than in the normal pregnancy group, but was significantly higher in the PE group during the third trimester.ConclusionsThe current results support that the TGF-β 1 869 T>C polymorphism was associated with the risk of PE. However, the number of eligible studies is small and more studies are needed to clarify whether this association can be detected on larger sample sizes and different populations. Owing to the heterogeneity between studies, no conclusion on the association between plasma TGF-β 1 level and PE risk can be drawn from this review. Further studies about the TGF-β 1 levels at different stages of pregnancy and the development of TGF-β 1 assay methodology are required to reveal the role of TGF-β 1 in the pathological development of PE.

TGFB1 Functional Gene Polymorphisms (C‐509T and T869C) in the Maternal Susceptibility to Pre‐eclampsia in South Indian Women

“…Keeping this in consideration, preceding studies attempted to examine any possible alterations of maternal TGF-b1 plasma levels in pre-eclamptic women. The results of some of these studies demonstrated elevated TGF-b1 concentrations in women with PE as compared to normotensive pregnant women, indicating that TGF-b1 synthesis and secretion might be dysregulated in PE pregnancies [18,20,21]. Additionally, some previous reports revealed altered levels of serum TGF-b1 based on the stage of pregnancy [18,21].…”

“…It is a 25-KDa homodimeric protein and is believed to control proliferation and differentiation of several cell types including foetal cytotrophoblasts and regulation of trophoblast invasion [16,17]. TGF-b1 has been shown to influence embryonic growth and development, apoptosis of endothelial cells and has recently been proposed to be one of the candidate genes for PE [18]. More importantly, this gene is considered as one of the master regulators for monitoring the number of the FOXP3 + regulatory T cells (Tregs), which play a crucial role in the maintenance of selftolerance, physiological immune responses and also mediate maternal tolerance to the foetus.…”

Transforming Growth Factor – Β1 and Pre-Eclampsia: Perspectives for Novel Therapeutic Modalities

“…Two current publications dealing with populations of varying ethnicities, point out towards reduced levels of TGF-β1 in the second trimester of pregnancy and increased levels during the third trimester and post-delivery in PE women, whereas the scenario is reported to be opposite in normal pregnancies [32,33] (Figure 1a). In the light of the existing literature and based on the functional significance of the SNPs studied, Goske et al, argue that the intermediary levels associated with heterozygous genotype confer a selective advantage and might protect women from PE, though their study did not involve measurement of serum TGF-β1 levels [22,23].…”

“…It also influences embryonic growth, development as well as apoptosis of endothelial cells. Fundamentally, this gene is considered as one of the master regulators for monitoring the number ofFOXP3+ regulatory T cells [Tregs], which play a crucial role in the maintenance of selftolerance, physiological immune responses and moreover mediates maternal tolerance to the paternal antigens of the foetus [11][12][13].…”

Comparison of Transforming Growth Factor-Beta 1 Concentration in Preeclampsia and Normal Pregnancy Women

“…(8) Meanwhile, another study showed that TGF-β1 was significantly lower in the preeclamptic group than in normal pregnancy. (9) In another side, Enquobahrie, et al, reported that Zimbabwe women with preeclampsia tend to have a higher TGF-β1 than normal pregnant women. 10The possibility of TGF-β1 as a marker for preeclampsia and the inconsistent results which were found in the previous studies have intrigued the writers to study the differences in mean serum levels of TGF-β1 in the preeclamptic patients and normal pregnancies.…”