Transforming Growth Factor – Β1 and Pre-Eclampsia: Perspectives for Novel Therapeutic Modalities Parveen Jahan 1 , Goske Deepthi 2 , Kamakshi Chaithri Ponnaluri 2 and Komaravalli Prasanna Latha 2 1 Department of Zoology, MANUU, Hyderabad-32, Telangana State, India 2 Department of Genetics, Osmania University, Hyderabad-07, Telangana State, India * Corresponding author: Parveen Jahan, Department of Zoology, MANUU, Hyderabad-32, Telangana State, India, Tel: 9885186923; E-mail: dr.pjahan@gmail.com Received date: February 17, 2016, Accepted date: March 7, 2016, Published date: March 10, 2016 Copyright: ©2016 Jahan P, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Breakdown in the immunoregulatory mechanism as well as dysregulated angiogenesis are critical contributors to the obstetric disorder, Pre-eclampsia [PE]. The pleiotropic cytokine, Transforming Growth Factor-β1 [TGF-β1], with its immunosuppressive and angiogenic functions appears to be a promising candidate for prospective therapies in PE, as gleaned from a survey of candidate gene association and biochemical investigations. The current article endows with a background and gives inkling for the plausible therapeutic strategies for PE employing TGF-β1, given the veracity that proper curative procedures are not yet existent for this disorder. Keywords: Pre-eclampsia; Transforming Growth Factor–β1; Gene Polymorphisms; Terapeutics Introduction Pre-eclampsia [PE] is a pregnancy specifc vascular disorder resulting in considerable maternal and perinatal morbidity and mortality. Clinically and symptomatically PE is characterized by hypertension and proteinuria afer the 20 th week of gestation. Te incidence of PE in the United States and European countries ranges from 2-5% and the incidence are much higher in the developing nations, 8-10% of all pregnancies in India [1]. PE is estimated to be the leading cause of maternal mortality in Latin America [2-4]. Descriptions of various pregnancy related physiological abnormalities were made as early as the 4 th century and it was only during the 18 th century, that eclampsia was distinguished from epilepsy. Since then (circa. 19 th century), classifcation of eclampsia continued to be refned and the term Pre-eclampsia was introduced in medical textbooks afer 1903 [5]. Te present classifcation of PE is based on the report published in the year 2000 by the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy [6]. Manifestation of PE is deemed to be a complex disease process encompassing interplay of genetic, environmental, and immunoregulatory factors [7]. Foremost among a host of factors to beget PE are dysregulated angiogenesis and accentuated maternal systemic T1 type of infammatory response. In an efort to comprehend the genetic basis of PE, a recently performed genome- wide analysis suggested TGFB1 as one of the key candidate genes for PE [8-10]. Further, a growing body of evidence confrms that TGF-β1, a25KDa homodimeric protein gains prominence in the pathogenesis of PE, by virtue of its pleiotropic nature. TGF-β1 is believed to control proliferation and diferentiation of several cell types including foetal cytotrophoblasts and regulation of trophoblast invasion. It also infuences 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 self- tolerance, physiological immune responses and moreover mediates maternal tolerance to the paternal antigens of the foetus [11-13]. A recent report by Goske et al., with an impressive sample size showed an association of two specifed polymorphic variants of TGFB1 gene with PE and emphasized the importance of carrying out further follow-up studies taking multiple immunoregulatory markers into consideration [14]. Investigations of such nature concurrently might provide insights into the underlying pathophysiology of the disease and novel drug targets. Polymorphic variants of TGFB1 gene and serum levels of TGF-β1 in PE Genetic polymorphisms in TGFB1 gene, which is mapped to human chromosome 19 [19q13.1-13.3] [15], have been studied for their association with PE. A couple of SNPs each in the promoter [-800G>A and -509C>T] and in the coding region [+869T>C and +915G>C] of TGFB1 gene were the widely explored variants for their infuence on PE, among various ethnic groups [16-21]. Owing to their location and signifcance, these gene variants were experimentally demonstrated to impact the circulating levels of TGF-β1 [22-23]. Te latest association study of Goske et al., has reported a signifcant link between TGFB1 T- T and C-C haplotype blocks [corresponding to -509C>T and +869T>C polymorphisms] and PE in south Indian women. Analyses of circulating concentrations of TGF-β1 have been performed in patients with PE, which however, have engendered inconsistent results perchance due to variation in the sampling methodology and/or gestational age [24-31]. 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). Jahan et al., Immunother Open Acc 2016, 2:1 DOI: 10.4172/2471-9552.1000113 Short Communication Open Access Immunother Open Acc ISSN:2471-9552 IMT, an open access journal Volume 2 • Issue 1 • 1000113 Immunotherapy: Open Access I m m u n o t h e r a p y : O p e n A c c e s s ISSN: 2471-9552