Nina Rogenhofer1, Lara R M Nienaber1, Lea C Amshoff2, Nadia Bogdanova2, David Petroff3, Peter Wieacker2, Christian J Thaler1, Arseni Markoff4. 1. Division of Gynecological Endocrinology and Reproductive Medicine, Department of Gynecology and Obstetrics, Klinikum der Ludwig-Maximilians-Universität, Munich, Campus Grosshadern, D-81377, Munich, Germany. 2. Insititute of Human Genetics, UKM and WWU Muenster, Vesaliusweg 12-14, 48149, Muenster, Germany. 3. Clinical Trial Centre, University of Leipzig, 04017, Leipzig, Germany. 4. Insititute of Human Genetics, UKM and WWU Muenster, Vesaliusweg 12-14, 48149, Muenster, Germany. markoff@uni-muenster.de.
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.
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.
Authors: G Tiscia; D Colaizzo; G Favuzzi; P Vergura; P Martinelli; M Margaglione; E Grandone Journal: Mol Hum Reprod Date: 2012-06-07 Impact factor: 4.025
Authors: Michael Krawczak; Susanna Nikolaus; Huberta von Eberstein; Peter J P Croucher; Nour Eddine El Mokhtari; Stefan Schreiber Journal: Community Genet Date: 2006
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