The role of FAS, FAS-L, BAX, and BCL-2 gene polymorphisms in determining susceptibility to unexplained recurrent pregnancy loss

Abstract

Purpose Idiopathic recurrent pregnancy loss (RPL) is a multifactorial reproductive disorder where an impaired control of apoptosis is likely involved. Triggering the cell death mechanism occurs in a spatiotemporal manner and is strongly related to a healthy pregnancy. Single nucleotide polymorphisms (SNPs) at the regulatory regions of genes are known to influence the expression patterns of apoptosis-related molecules. Methods A total of 296 unrelated female Brazilian patients were evaluated for clinical-demographic variables and genetic factors: 140 women who had experienced an unexplained RPL (with at least two consecutive abortions) and 156 healthy multiparous women. In all patients, six SNPs were evaluated in genes of apoptosis-related pathways: FAS (rs2234767, rs1800682), FAS-L (rs763110, rs5030772), BAX (rs4645878), and BCL-2 (rs2279115) by PCR followed by a restriction fragment length polymorphism (RFLP)-based analysis. Results The BAX-248GA genotype is independently associated with idiopathic RPL [adjusted OR = 0.30, 95% CI 0.13-0.70, P = 0.005] susceptibility. In the same multivariate model, the variables ethnicity, smoking, and alcohol consumption were statistically associated with RPL susceptibility (P < 0.05). No association with RPL susceptibility was reported for the remaining SNPs. Conclusion Our study is the first to evaluate the role of the main SNPs from both the extrinsic and intrinsic apoptosis pathways in RPL susceptibility. The association of BAX-248G/A with RPL susceptibility suggests that maternal predisposition for RPL has an essential contribution from genes involved in the delicate balance of endometrium cell turnover (cell death/proliferation). Therefore, apoptotic genes may represent promising targets for future studies on healthy pregnancies and the spectrum of pregnancy disorders.

RETRACTED ARTICLE: Exposure to pesticide components causes recurrent pregnancy loss by increasing placental oxidative stress and apoptosis: a case–control study

“…When apoptosis exceeds the growth of trophoblasts bad consequences happen including FGR, preeclampsia, and preterm birth 4 , 50 . In compliance with our findings, disturbance of apoptotic/anti-apoptotic proteins balance has been recognized as a key feature in cases with RPL 51 . Exposure to environmental toxins might result in this disturbance and consequently RPL 52 .…”

Genes of Inflammation and Placental Function GWAS Associated with Idiopathic Recurrent Miscarriage in the Kazakh Population

“…[ 14 ] It was shown that SNPs in the sequences of the above genes correlate with the phenomenon of miscarriage. [ 15 ] In particular, BAX-248GA is independently associated with iRM protection. The homozygous BAX-248AA genotype is more common in women with RM.…”

Induction of ligustrazine apoptosis of A549 cells through activation of death receptor pathway

“…Gene regulation in apoptosis is involved in numerous signaling pathways. Fas and its ligand, Fas-L, are membrane surface molecules closely related to apoptosis, and the Fas/Fas-L system is integral to mediating apoptosis and has been primarily used to study tumor therapy (17,18). Both vivo and in vitro studies have demonstrated that Fas mAb can bind to Fas, resulting in the death of cells expressing Fas.…”

“…High expression of Fas on the cell membrane is thus highly indicative of the susceptibility of Fas signaling pathway to induce apoptosis; however, the cutoff value between tumor cells is not uniform. Studies have shown that several molecules including Bcl-2 family, c-myc, Ras, and Fap-1 may participate in Fas-mediated apoptosis (18,(20)(21)(22)(23). The death of cells with a surface expression of Fas molecules may be induced by T lymphocytes positive for Fas-L (24).…”