TGF-β1 promoter functional gene polymorphism-509 C/T in the maternal susceptibility to recurrent pregnancy loss in South Indian women

Transforming growth factor beta 1 (TGF-beta 1) is an anti-inflammatory pleiotropic cytokine that regulates implantation and adhesion of trophoblasts to the extracellular matrix. It regulates the balance of Th1/Th2 cytokines and the generation of anti-inflammatory peripheral regulatory T cells (FOXP3 + Tregs), which is necessary for a healthy pregnancy. Single nucleotide polymorphisms (SNP) affecting TGF-beta 1 production/function may predispose to pregnancy loss. The aim of this study is to evaluate the association between the TGF-beta 1 -509C/T polymorphism, its serum concentrations, and recurrent pregnancy loss. The study comprised 150 RPL cases and 150 healthy controls for genotyping TGF-beta 1 -509C/T polymorphism using the Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR). Serum concentrations of TGF-beta 1 protein were estimated by enzyme-linked immunosorbent assay. From our study, women with CT genotype exhibited a protective role against RPL [OR (95 % CI) = 0.48(0.30-0.76), p = 0.002], while women with TT genotype had a significantly higher risk among RPL patients and exhibited twofold increased risk [OR (95 % CI) = 2.34(1.37-4.01), p = 0.002]. Observation of patient's follow-up data revealed a significant relation with CT genotype of unfavorable pregnancy outcome (CT vs. CC + TT, OR 2.46, 95 % C.I: 1.11-5.43, p = 0.039). Further, variant allele T was significantly elevated in women with unfavorable pregnancy compared with favorable pregnancy outcome, indicating considerable association of T allele in unfavorable pregnancy outcome (T vs. C, OR: 2.68, 95 % C.I: 1.52-4.74, p = <0.001). Serum concentrations of TGF-beta 1 have shown significant variation between patients and controls, as well as among RPL patients with favorable and unfavorable pregnancy outcome in correspondence to each genotype CC, CT, and TT (p < 0.05). Furthermore, genotype-dependent variation was observed within both the patient and control groups; however, this variation was not observed among RPL women with favorable and unfavorable pregnancy outcome. Our investigation revealed a significant influence of TGF-beta 1 C-509 T polymorphism on RPL risk in South Indian women.