Dataset Information

Assessment of M2/ANXA5 haplotype as a risk factor in couples with placenta-mediated pregnancy complications.

ABSTRACT:

Purpose

The aim of this study was to confirm the associated M2/ANXA5 carrier risk in women with placenta-mediated pregnancy complications (PMPC) and to test their male partners for such association. Further analysis evaluated the influence of maternal vs. paternal M2 alleles on miscarriage.

Methods

Two hundred eighty-eight couples with preeclampsia (PE), intrauterine growth restriction (IUGR), or premature birth (PB) were recruited (n = 96 of each phenotype). The prevalence of the M2 haplotype was compared to two control cohorts. They included a group of women with a history of normal pregnancy without gestational pathology (Munich controls, n = 94) and a random population sample (PopGen controls, n = 533).

Results

Significant association of M2 haplotype and pregnancy complications was confirmed for women and for couples, where prevalence was elevated from 15.4 to 23.8% (p < 0.001). Post hoc analyses demonstrated an association for IUGR and PB individually. A strong link between previous miscarriages and M2 carrier status was identified which may explain the predisposition to placental pregnancy complication. M2/ANXA5 appears to be a risk factor for adverse pregnancy outcomes related, but not limited to miscarriages, with similar prevalence in women and their male partners.

Conclusion

These findings support the proposed physiological function of ANXA5 as an embryonic anticoagulant that appears deficient in contiguous specter of thrombophilia-related pregnancy complications culminating more frequently in miscarriage in a maternal M2 carrier background.

SUBMITTER: Rogenhofer N

PROVIDER: S-EPMC5758464 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Publications

Assessment of M2/ANXA5 haplotype as a risk factor in couples with placenta-mediated pregnancy complications.

Rogenhofer Nina N Nienaber Lara R M LRM Amshoff Lea C LC Bogdanova Nadia N Petroff David D Wieacker Peter P Thaler Christian J CJ Markoff Arseni A

Journal of assisted reproduction and genetics 20170913 1

<h4>Purpose</h4>The aim of this study was to confirm the associated M2/ANXA5 carrier risk in women with placenta-mediated pregnancy complications (PMPC) and to test their male partners for such association. Further analysis evaluated the influence of maternal vs. paternal M2 alleles on miscarriage.<h4>Methods</h4>Two hundred eighty-eight couples with preeclampsia (PE), intrauterine growth restriction (IUGR), or premature birth (PB) were recruited (n = 96 of each phenotype). The prevalence of the ...[more]

PMID: 28900802

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Project description:Data on the temporal dynamics of human placental gene expression is scarce. We have completed the first whole-genome profiling of human placental gene expression dynamics (GeneChips, Affymetrix®) from early to mid- gestation (10 samples; gestational weeks 5 to 18) and report 154 genes with considerable change in transcript levels (FDR P<0.1). Functional enrichment analysis revealed >200 GO categories that are statistically over-represented among 105 genes with dynamically increasing transcript levels. Analysis in an extended sample (n=43; gestational weeks 5 to 41) conformed a highly significant (FDR P<0.05) expressional peak in mid-gestation placenta for ten genes: BMP5, CCNG2, CDH11, FST, GATM, GPR183, ITGBL1, PLAGL1, SLC16A10, STC1. A central hypothesis of our study states that the aberrant expression of genes characteristic to mid-gestation placenta may contribute to affected fetal growth, maternal preeclampsia (PE) or gestational diabetes (GD). The gene STC1 coding for Stanniocalcin 1 (STC1) was identified with a sharp placental expressional peak in mid-gestation, increased mRNA levels at term and significantly elevated STC1 protein levels in post-partum maternal plasma in all pregnancy complications. The highest STC1 levels were identified in women, who developed simultaneously PE and delivered an SGA baby (median 731 vs 418 pg/ml in controls; P=0.001). CCNG2 and LYPD6 exhibited significantly increased placental mRNA expression and enhanced intensity of immunohistochemistry staining in placental sections all studied in GD and PE cases. Aberrant expression of mid-gestation specific genes in pregnancy complications at term indicates the importance of the fine-scale tuning of the temporal dynamics of transcription regulation in placenta. Observed significantly elevated plasma STC1 in complicated pregnancies warrants further investigations of its potential as a biomarker. Interestingly, a majority of genes with high expression in mid-gestation placenta have also been implicated in adult complex disease. This observation promotes a recently opened discussion on the role of placenta in developmental programming. 4 samples; this submission is extension of our earlier study (accession GSE22490).

Dataset Information

Assessment of M2/ANXA5 haplotype as a risk factor in couples with placenta-mediated pregnancy complications.

Purpose

Methods

Results

Conclusion

Publications

Assessment of M2/ANXA5 haplotype as a risk factor in couples with placenta-mediated pregnancy complications.

Similar Datasets

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