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

  • Genetics
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Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

Annexin A5 (ANXA5) is a protein abundantly expressed in normal placenta where it contributes to the healthy outcome of a pregnancy. Lower ANXA5 levels have been observed in M2/ANXA5 haplotype carrying chorion. Consequently, this study aimed to assess the potential association of M2 maternal carrier status with the risk of recurrent pregnancy loss (RPL), the timing of miscarriages, and other obstetric complications, for the first time in a population from Latin America.

Methods

This study was designed as a prospective recruitment of RPL patients with post hoc analysis. The distribution of the M2/ANXA5 haplotype was compared between a group of 229 Argentine women with RPL and 100 parous controls, and was further analyzed in subgroups of patients stratified according to the timing of miscarriages and in relation to other obstetric complications.

Results

No significant differences were found in the distribution of M2 haplotype among either RPL patients or the subgroups with embryonic, early fetal, or late fetal losses compared to parous controls. Notwithstanding, maternal M2/ANXA5 was found to be independently associated with a higher risk of suffering intrauterine growth restriction (IUGR) and/or preeclampsia (PE). Simultaneously, the presence of inherited and/or acquired thrombophilia also proved to be an independent risk factor for these.

Conclusions

The association found between the maternal carriage of the M2/ANXA5 haplotype and an elevated risk of IUGR and/or PE supports the hypothesis that carrier status of this haplotype and the consequently reduced placental ANXA5 expression might be responsible, at least partially, for the onset of these gestational vascular complications.

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Author notes

  1. Arseni Markoff and Gabriela de Larrañaga contributed equally to this work.

Authors and Affiliations

  1. Hemostasis and Thrombosis Laboratory, Hospital of Infectious Diseases “Dr Francisco J. Muñiz”, Uspallata 2272, C1282AEN, Buenos Aires, Argentina

    Federico Aranda, Silvia Perés Wingeyer & Gabriela de Larrañaga

  2. Section of Autoimmune Diseases, Thrombophilia and Pregnancy, Acute Care Hospital “Dr Carlos G. Durand”, Av. Díaz Vélez 5044, C1405DCS, Buenos Aires, Argentina

    Sebastián Udry & José Omar Latino

  3. Institute of Human Genetics, University Clinic Muenster, Vesaliusweg 12, 48149, Muenster, Germany

    Lea Christina Amshoff, Nadja Bogdanova, Peter Wieacker & Arseni Markoff

Authors
  1. Federico Aranda
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  2. Sebastián Udry
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  3. Silvia Perés Wingeyer
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  4. Lea Christina Amshoff
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  5. Nadja Bogdanova
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  7. José Omar Latino
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  9. Gabriela de Larrañaga
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Correspondence to Federico Aranda.

Ethics declarations

This field study to verify possible association of M2/ANXA5 was designed as a prospective recruitment of RPL patients with post hoc analysis that was approved by the ethical committees of the institutions involved and was performed according to the principles of the Declaration of Helsinki. Informed consent was obtained from all participants.

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Aranda, F., Udry, S., Perés Wingeyer, S. et al. Maternal carriers of the ANXA5 M2 haplotype are exposed to a greater risk for placenta-mediated pregnancy complications. J Assist Reprod Genet 35, 921–928 (2018). https://doi.org/10.1007/s10815-018-1142-4

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  • DOI: https://doi.org/10.1007/s10815-018-1142-4

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