FAS A‐670G and Fas ligand IVS2nt A 124G polymorphisms are significantly increased in women with pre‐eclampsia and may contribute to HELLP syndrome: a case‐controlled study

Raguema, Nozha; Zitouni, Hédia; Gannoun, Marwa Ben Ali; Benletaifa, Dhafer; Almawi, WY; Mahjoub, Touhami; Lavoie, Julie L.

doi:10.1111/1471-0528.15412

Cited by 13 publications

(12 citation statements)

References 31 publications

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“…Consistent with these findings, we and others have also shown that the expression of FAS and FASL in serum and in maternal lymphocytes also occurs in preeclampsia (Miko et al, 2009;Raguema et al, 2018). We also described the polymorphisms of FAS-670A/G and FASL IVS2nt124A/G genes in the lymphocytes of pregnant women with preeclampsia.…”

Section: Apoptosis In Preeclampsiasupporting

confidence: 89%

Immune and Apoptosis Mechanisms Regulating Placental Development and Vascularization in Preeclampsia

2020

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Preeclampsia is the most severe type of hypertensive disorder of pregnancy, affecting one in 10 pregnancies worldwide and increasing significantly maternal and neonatal morbidity and mortality. Women developing preeclampsia display an array of symptoms encompassing uncontrolled hypertension and proteinuria, with neurological symptoms including seizures at the end of pregnancy. The main causes of preeclampsia are still unknown. However, abnormal placentation and placenta vascularization seem to be common features in preeclampsia, also leading to fetal growth restriction mainly due to reduced placental blood flow and chronic hypoxia. An over activation of maternal immunity cells against the trophoblasts, the main cells forming the placenta, has been recently shown as an important mechanism triggering trophoblast apoptosis and death. This response will further disrupt the remodeling of maternal uterine arteries, in a first stage, and the formation of new placental vessels in a later stage. A consequent chronic hypoxia stress will further contribute to increase placental stress and exacerbate systemic circulatory changes in the mother. The molecular mechanisms driving these processes of apoptosis and anti-angiogenesis are also not well-understood. In this review, we group main evidences suggesting potential targets and molecules that should be better investigated in preeclampsia. This knowledge will contribute to improve therapies targeting a better placenta formation, having a positive impact on maternal disease prevention and on fetal development.

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Section: Apoptosis In Preeclampsiasupporting

confidence: 89%

Immune and Apoptosis Mechanisms Regulating Placental Development and Vascularization in Preeclampsia

2020

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Michita

Zambra

Fraga

et al. 2019

J Assist Reprod Genet

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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.

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“…Nine citations were excluded due to the following reasons: two citations did not provide detailed genotyping data; four studied other diseases, and three was not case–control study. Eventually, we identified seven eligible citations [14–20] (834 cases and 1072 controls) containing nine studies. Selection for qualified studies was shown in Figure 1.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, several studies [14–20] reported the association between single-nucleotide polymorphisms (SNPs) in Fas, FasL genes and the risk of preeclampsia. However, the results were inconsistent and conflicting.…”

Section: Introductionmentioning

confidence: 99%

“…However, the results were inconsistent and conflicting. For instance, Raguema et al [14], Salimi et al [16], Nasr et al [17], Ciarmel et al [19], and Sziller et al [20] all found that Fas -670 A/G polymorphism increased the risk of preeclampsia, whereas Masoumi et al [15] and Lasabova et al [18] reported that Fas -670 A/G polymorphism was not related to preeclampsia susceptibility. Therefore, we conducted this meta-analysis to verify whether Fas and FasL gene polymorphisms were associated with preeclampsia risk.…”

Section: Introductionmentioning

confidence: 99%

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The relationship between Fas and Fas ligand gene polymorphism and preeclampsia risk

Wang

Lian

2019

Bioscience Reports

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Preeclampsia is an idiopathic multisystem disorder with partial genetic and immunological etiology. Several studies investigated the association between various single-nucleotide polymorphisms (SNPs) in Fas and Fas ligand (FasL) genes and the risk of preeclampsia. However, they achieved inconsistent results. Therefore, we conducted a meta-analysis by systematically searching the Cochrane Library, PubMed and Embase databases and assessed this association by calculating pooled odds ratios with 95% confidence interval to reach a more trustworthy conclusion. Subgroup analyses by genotype methods and source of controls (SOC) were also conducted. Seven citations containing nine studies were included for four SNPs (Fas -670 A/G, FasL 124A/G, FasL -844C/T, Fas -1377 G/A) in this meta-analysis. Our data suggested the G allele and genotype GG of the Fas -670 A/G polymorphism, GG genotype of the FasL 124A/G polymorphism, and TT genotype of the FasL -844C/T polymorphism increased the risk of preeclampsia. Stratification analyses by genotype methods and SOC also indicated that Fas -670 A/G polymorphism was related to increased risk for preeclampsia. In conclusion, Fas and FasL gene polymorphisms play important roles in the development of preeclampsia. Further well-designed studies in other races are needed to confirm the findings of this meta-analysis.

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FAS A‐670G and Fas ligand IVS2nt A 124G polymorphisms are significantly increased in women with pre‐eclampsia and may contribute to HELLP syndrome: a case‐controlled study

Abstract: Polymorphisms in the Fas and FasL genes are associated with increased risk of pre-eclampsia and HELLP syndrome.

Cited by 13 publications

References 31 publications

Immune and Apoptosis Mechanisms Regulating Placental Development and Vascularization in Preeclampsia

Immune and Apoptosis Mechanisms Regulating Placental Development and Vascularization in Preeclampsia

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

The relationship between Fas and Fas ligand gene polymorphism and preeclampsia risk

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