Paternal and maternal carriage of the annexin A5 M2 haplotype are equal risk factors for recurrent pregnancy loss: a pilot study

Rogenhofer, Nina; Engels, Laura; Bogdanova, Nadja; Tüttelmann, Frank; Markoff, Arseni; Thaler, Christian J.

doi:10.1016/j.fertnstert.2012.04.026

Cited by 46 publications

(72 citation statements)

References 37 publications

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“…This confirms a pilot study that showed that the M2 haplotype confers the same relative risk to carriers of both sexes, based on 30 couples (Rogenhofer et al 2012) and a more recent study based on 109 couples (Tüttelmann et al 2013). Based on the findings from these studies, screening for the M2 haplotype in both partners in RM couples should be considered.…”

Section: Discussionsupporting

confidence: 84%

Investigation of the Annexin A5 M2 haplotype in 500 white European couples who have experienced recurrent spontaneous abortion

Demetriou

Abu-Amero

White

et al. 2015

Reproductive BioMedicine Online

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Annexin A5 is a placental anti-coagulant protein that contains four nucleotide substitutions (M2 haplotype) in its promoter. Studies have shown that this haplotype is a risk factor for recurrent miscarriage (RM). Our aim was to investigate the influence of the M2 haplotype in the gestational timing of miscarriages, assessing the paternal risk and investigate for relationships with known risk factors. Five hundred white European couples with three or more consecutive miscarriages and two fertile control groups were selected for this study.The allele frequency of M2 was found to be significantly higher among early RM patients than among controls (P=0.002) and there was no difference between controls and patients with late miscarriages. Moreover, there was no difference between RM patients who had a live birth or no live births or between patients who were positive or negative for known risk factors. Male and female partners in each group had similar allele frequencies of M2. In conclusion, the M2 haplotype is a risk factor for early miscarriages, before the 12 th week of gestation and confers about the same relative risk to carriers of both sexes. Having one or more M2 allele(s) in combination with other risk factors further increases the RM risk.

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Section: Discussionsupporting

confidence: 84%

Investigation of the Annexin A5 M2 haplotype in 500 white European couples who have experienced recurrent spontaneous abortion

Demetriou

Abu-Amero

White

et al. 2015

Reproductive BioMedicine Online

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“…The odds ratios of M2-carrying RPL patients from this study, 1.4 with population controls and 1.9 with parous women, are similar to these of European RPL cohorts, 1.5 to 2.5 with population controls and 3 to 5 with parous controls [5,21,22], as well as to the reported odds ratio of 2.4 with parous women from the Japanese study [20]. Attributable predisposition of male M2 carriers in Malay RPL couples is thus in general agreement with these previous studies, supporting the proposed pathophysiological expression of M2/ANXA5 in impediment of embryonic anticoagulation.…”

Section: Discussionsupporting

confidence: 79%

“…Male partners of 146 of these women agreed to participate in the study. RPL subjects were pre-screened for potential causes of their repeated pregnancy loss as described previously [21,24]. Uterine anomalies and endocrine dysfunctions (polycystic ovary syndrome according to the Rotterdam criteria [25] and thyroidal dysfunctions, if anamnestic) were not included.…”

Section: Study Populationsmentioning

confidence: 99%

“…However, the criteria for RPL subjects varied slightly between the studies such as the definition of RPL and categories of embryonic development. In addition to available evidence supporting reduced expression of ANXA5 in chorionic placenta of RPL women, who were M2/ANXA5 carriers [18,19], the male M2/ANXA5 carriers in RPL couples also showed a rather similar risk that would corroborate impeded embryonic anticoagulant function [5,[21][22][23].…”

Section: Introductionmentioning

confidence: 99%

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Genetic analysis of the M2/ANXA5 haplotype as recurrent pregnancy loss predisposition in the Malay population

Ang

Kathirgamanathan

Ch’ng

et al. 2017

J Assist Reprod Genet

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Purpose The aim of this study was to evaluate a new predisposition factor, M2/ANXA5 (RPRGL3), in recurrent pregnancy loss (RPL) patients of Malay origin, since it was previously known that the prevalence of this condition is relatively high among the Malay population of Malaysia, where conventional hereditary thrombophilia factors have been generally ruled out. Methods A total of 232 women who had experienced ≥2 unexplained RPL and 141 available male partners were recruited, with 360 healthy Malay and 166 parous female controls. Prevalence of M2 carriage and RPL odds ratios were calculated in (a) control and patient groups; (b) clinically defined subgroups in categories of pregnancy loss, primary, secondary, and tertiary; and (c) timing of pregnancy loss in early, ≤15th gestation week and Blate^fetal losses, and >15th gestation week subgroups.Results Both male and female subjects had similar M2/ ANXA5 allele frequencies. The carrier rate of M2/ANXA5 for the general Malay population was 42.2 and 34.9% for parous controls. These carrier rates compared to Malay RPL subjects (52% M2 carriers) resulted in elevated odds ratios (95% confidence interval) of 1.53 (1.1 to 2.1) and 1.97 (1.3 to 3.1) accordingly for early fetal losses. Moreover, exceeding copy numbers of M2/ANXA5 alleles seemed to afflict a greater chance of RPL in couples, especially when both partners were M2 carriers. Conclusion This study confirmed the proposed role of M2/ ANXA5 as embryonic, genetically associated thrombophilia predisposition factor for early RPL among ethnic Malay of Malaysia.Keywords Annexin A5 . M2/ANXA5 . Recurrent pregnancy loss (RPL) . MiscarriageElectronic supplementary material The online version of this article

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“…The haplotype is present in about 15% of European populations studied so far Tüttelmann et al, 2013), in 11% of the Japanese (Miyamura et al, 2011), and confers about a two-fold elevated RSA risk in relevant patient groups. Available evidence links carriage of M2/ANXA5 with reduced expression of ANXA5 in chorionic placenta Markoff et al, 2010), and associated similar risks of male carriers in couples who have experienced RSA point to a possibly impeded embryonic anticoagulant function (Rogenhofer et al, 2012;Tüttelmann et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

M2/ANXA5 haplotype as a predisposition factor in Malay women and couples experiencing recurrent spontaneous abortion: a pilot study

Hock

Bogdanova²,

Cheen

et al. 2015

Reproductive BioMedicine Online

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Recurrent spontaneous abortion (RSA) is a prevalent condition among the Malay population of Malaysia, where carriage risk of conventional hereditary thrombophilia factors has been generally ruled out. The contribution of M2/ANXA5, a common haplotype in the annexin A5 gene promoter, was evalauted for RSA in Malay. Seventy-seven women who had experienced two or more unexplained RSA and 41 available male partners were selected for study, with 360 population controls recruited from healthy Malay individuals. Incidence of M2 carriage and odds ratios were calculated between control and patient groups, and clinically defined subgroups and RSA risk was evaluated. M2/ANXA5, found in 42.2% of the general Malay population, was associated with greater risks for women with primary and secondary RSA with early (gestational week 5-15) losses. The risk was somewhat higher in Malay couples when both partners were carriers and a trend of higher prevalence was seen for the male partners patients who had experienced RSA. M2 carriage seems to be a risk factor with unusually high incidence in Malay women and couples with primary and secondary RSA with 'early' spontaneous abortions. The associated male partner risk confirms the proposed role of M2/ANXA5 as a genetic trait impeding embryonic anticoagulation.

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Paternal and maternal carriage of the annexin A5 M2 haplotype are equal risk factors for recurrent pregnancy loss: a pilot study

Cited by 46 publications

References 37 publications

Investigation of the Annexin A5 M2 haplotype in 500 white European couples who have experienced recurrent spontaneous abortion

Investigation of the Annexin A5 M2 haplotype in 500 white European couples who have experienced recurrent spontaneous abortion

Genetic analysis of the M2/ANXA5 haplotype as recurrent pregnancy loss predisposition in the Malay population

M2/ANXA5 haplotype as a predisposition factor in Malay women and couples experiencing recurrent spontaneous abortion: a pilot study

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