FAS and FAS-L Genotype and Expression in Patients With Recurrent Pregnancy Loss

Abstract

We assessed FAS and FAS-L gene polymorphisms and messenger RNA (mRNA) levels in patients with recurrent pregnancy loss (RPL). This case-control study compared 129 women with RPL with 235 healthy multiparous women (control group). Genomic DNA and total mRNA were extracted from whole blood, and polymorphisms genotyping was performed by polymerase chain reaction (PCR). Messenger RNA expression levels were analyzed by real-time PCR. Data were analyzed by chi-square and Fisher exact tests; P < .05 was considered significant. There were no significant differences in the FAS (670 A/G) genotype or allelic frequencies between the RPL and control groups. We found significant differences in the FAS-L (844 C/T) genotype and allelic frequencies between women with RPL and controls. Patients with RPL had significantly higher FAS-L expression. Our data suggest that FAS-L gene polymorphism is associated with increased susceptibility to RPL. Moreover, women with RPL seem to abnormally express FAS-FAS-L molecules.

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

“…It has been reported that extravillous trophoblast cells (EVTs) express FAS-L [17], thus implying that FAS-L expression in both maternal and fetal cells represents an additional mechanism related to the immunotolerance phenomenon in pregnancy [18]. Genetic variants in the regulatory region of FAS and FAS-L genes have been shown to impact gene expression patterns and the susceptibility of many immunerelated disorders and pregnancy disorders, including RPL [19][20][21][22][23][24][25][26][27]. FAS-670A/G and FAS-1377G/A are single nucleotide polymorphisms (SNPs) that are located in the promoter region of FAS.…”

“…In pregnancy, previous studies have reported the high expression of apoptotic proteins in the chorionic villi from women with RPL [8,41], thus suggesting that imbalances between the proapoptotic and antiapoptotic stimuli are likely involved in RPL pathogenesis. Currently, studies evaluating the role of genetic variants in FAS, FAS-L, BAX, and BCL-2 on RPL susceptibility [21,22] are limited or even absent, and in most cases, a limited set of variants from a single apoptotic pathway was evaluated. Therefore, we evaluated whether SNPs in critical genes of the classical apoptosis pathway are associated with RPL risk in a Brazilian population.…”

Genetic Considerations in Recurrent Pregnancy Loss

“…The presence of a null allele for the most common HLA-G isoform as well as distinct polymorphisms in the HLA-G promoter region, have been associated with recurrent miscarriage, suggesting that a functional protein is necessary for reproduction (Aldrich et al 2001;Pfeiffer et al 2001). Polymorphisms in genes including p53, p72, leukemia inhibiting factor (LIF), FAS-L, and the vascular endothelial growth factor (VEGF) gene have also been linked to increased rates of implantation failure and are undergoing investigation to determine their potential roles in women with RPL (Dumont et al 2003;Steck et al 2004;Brooks et al 2007;Hu et al 2007;Goodman et al 2008;Banzato et al 2013;Fraga et al 2014). Despite evidence linking various polymorphisms in immune-related genes to pregnancy loss, these tests are not presently recommended as routine…”

Therapeutic effects of Wharton jelly‐derived mesenchymal stem cells on rat abortion models

“…We call these cases unexplained recurrent spontaneous abortion (URSA). The causes of RPL include uterine anatomical defects, uterine infections, chromosomal aberrations, hormonal disorders, hematological problems and immunological abnormalities, 1,2 in which the relationship between immune factors and RPL has become an area of intense research interest. However, abnormality of the maternal immune system may induce pre-eclampsia and RPL.…”