Maternal carriers of the ANXA5 M2 haplotype are exposed to a greater risk for placenta-mediated pregnancy complications

Aranda, Federico; Wingeyer, Silvia Perés; Amshoff, Lea C.; Bogdanova, Nadja; Wieacker, P.; Latino, José Omar; Markoff, Arseni; Larrañaga, Gabriela de

doi:10.1007/s10815-018-1142-4

Cited by 14 publications

(15 citation statements)

References 54 publications

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“…In line with such protective function in the blood clotting regulation, anti-AnxA5 autoantibodies are found in patients suffering from antiphospholipid syndrome [43], a disease that manifests clinically as recurrent thrombotic events and is associated with fetal loss [44]. The occurrence of AnxA5 autoantibodies [45] is also linked to autoimmune disorders [46] also observed in some patients suffering from multiple sclerosis or systemic lupus erythematosus.…”

Section: Coagulationmentioning

confidence: 90%

Annexins in Translational Research: HIDDEN Treasures to Be Found

Schloer¹,

Pajonczyk²,

Rescher³

2018

Preprint

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The vertebrate annexin superfamily (AnxA) consists of 12 members of a calcium (Ca 2+ ) and phospholipid binding protein family which share a high structural homology. In keeping with this hallmark feature, annexins have been implicated in the Ca 2+ -controlled regulation of a broad range of membrane events. In this review, we identify and discuss several themes of annexin actions that hold a potential therapeutic value, namely the regulation of the immune response and the control of tissue homeostasis, and that repeatedly surface in the annexin activity profile. Our aim is to identify and discuss those annexin properties which might be exploited from a translational science and specifically clinical point of view.

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Section: Coagulationmentioning

confidence: 90%

Annexins in Translational Research: HIDDEN Treasures to Be Found

Schloer¹,

Pajonczyk²,

Rescher³

2018

Preprint

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“…M2/ANXA5 haplotype, the third hereditary predisposition gene for thrombophilia-associated RPL , has been shown to be associated with unexplained RPL cases. The prevalence ranges from 11 % to 42 % among healthy individuals Aranda et al, 2018;Bogdanova et al, 2007;Demetriou et al, 2015;Hayashi et al, 2013;Miyamura et al, 2011;Nagirnaja et al, 2015;Rogenhofer et al, 2012;Tiscia et al, 2009;Tüttelmann et al, 2013). A recent meta-analysis demonstrates that a M2/ANXA5 woman carrier has 1.54 times the odds to experience RPL.…”

Section: Discussionmentioning

confidence: 99%

Development of cost-effective and accurate allele-specific PCR for determination of M2/ANXA5 haplotype in recurrent pregnancy loss

Ang

Rozhdestvensky

Markoff³

et al. 2021

APJMBB

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Repeated Pregnancy Loss (RPL) affects approximately 1 out of 20 pregnant women globally; it is traumatic for parents seeking parenthood with ensuing anxieties for the next pregnancy. M2/ANXA5 haplotype is a hereditary predisposition gene for thrombophilia-associated RPL; the association between M2/ANXA5 haplotype and RPL is further ascertained in a recent meta-analysis. Precision treatments have been proposed for RPL women with M2/ANXA5 haplotype. Therefore, screening for M2/ANXA5 haplotype is highly recommended as a panel of laboratory investigations for idiopathic RPL. To date, direct sequencing of PCR products is the most common method for the determination of M2/ANXA5 haplotype; this method is however tedious, expensive and time- consuming. Hereby, we demonstrate a simple and robust allele-specific PCR (AS-PCR) that detects two inherent SNPs in a single tube, which could serve as a routine genotyping tool for M2/ANXA5 haplotype. This test is rapid, only taking maximum 4 working hours to complete the analysis. Validation of the assay by 105 clinical DNA samples yields 100% concordance rate with the DNA sequencing results.

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“…18,19). These studies have included analysis of individuals from the United Kingdom, Estonia, Italy, Germany, Japan, and Argentina (1,5,6,10,11,18,19). However, very few studies have specifically evaluated patients undergoing infertility treatment (5).…”

Section: Discussionmentioning

confidence: 99%

“…uring the early stages of pregnancy, vascular remodeling between the placental villi and uterine wall is essential in establishing a circulatory system between the mother and fetus. The syncytiotrophoblasts of the placental tissue express annexin A5 (ANXA5) anticoagulant protein, which is essential in placental maintenance and repair (1,2). ANXA5 aids syncytiotrophoblasts in maintaining placental vasculature and blood fluidity.…”

mentioning

confidence: 99%

A novel test for annexin A5 M2 haplotyping in in vitro fertilization patients and preimplantation embryos

et al. 2021

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Objective: To develop a test for evaluating the annexin A5 M2 haplotype in in vitro fertilization patients and preimplantation embryos. Design: Test performance was measured by comparing Sanger sequencing of parental blood DNA and quantitative real-time polymerase chain reaction (qPCR) of saliva DNA, 3 fibroblast cell line 7-cell aliquots and their corresponding purified DNA, 123 trophectoderm biopsy samples, and DNA isolated from 1 embryonic stem cell line along with the Mendelian inheritance expectations, embryo Sanger sequencing, and single-nucleotide polymorphism (SNP) microarray-based linkage analysis. Setting: Preimplantation genetic testing laboratory research on IVF patient and embryo DNA. Patient(s): An assay was developed for the detection of the M2 haplotype on saliva samples of 6 in vitro fertilization patients. In addition, 13 patients who underwent preimplantation genetic testing with data on parental and embryo biopsy DNA available for research use were evaluated. Intervention(s): None. Main Outcome Measure(s): The concordance rates between Sanger sequencing, SNP array-based linkage analysis, and Mendelian inheritance expectations with qPCR. Result(s): The concordance rate between Sanger sequencing and qPCR was 100% on parental blood DNA and saliva DNA. The sample concordance rate between all replicates of 7-cell aliquots was 100%. The sample concordance rate between 3 cell lines used to prepare 7cell aliquots and purified genomic DNA was 100%. The concordance rate between qPCR and Sanger sequencing results from a single trophectoderm biopsy and isolated embryonic stem cell line was 100%. The concordance rate of trophectoderm biopsy qPCR results and expectations from Mendelian inheritance rules was 97%; however, when SNP array-based linkage analysis was included, the concordance rate reached 100%. Conclusion(s):This study resulted in the development of a convenient saliva collection method and qPCR-based genotyping method to screen for the M2 haplotype. In addition, a novel method for testing preimplantation embryos has been established, providing an alternative to the use of low molecular weight heparin, through selection of embryos without the M2 haplotype.

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Maternal carriers of the ANXA5 M2 haplotype are exposed to a greater risk for placenta-mediated pregnancy complications

Cited by 14 publications

References 54 publications

Annexins in Translational Research: HIDDEN Treasures to Be Found

Annexins in Translational Research: HIDDEN Treasures to Be Found

Development of cost-effective and accurate allele-specific PCR for determination of M2/ANXA5 haplotype in recurrent pregnancy loss

A novel test for annexin A5 M2 haplotyping in in vitro fertilization patients and preimplantation embryos

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