Inherited thrombophilia and pregnancy loss. Study of an Argentinian cohort

Wingeyer, Silvia Perés; Aranda, Federico; Latino, José Omar; Larrañaga, Gabriela de

doi:10.1016/j.medcle.2017.12.044

Cited by 8 publications

(15 citation statements)

References 28 publications

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“…Abnormal coagulation can inhibit implantation and initiate miscarriage. In the past decades, several studies have suggested that polymorphisms of thrombophilic factors such as G1691A encoded by FVL , G20210A encoded by F2 and C677T encoded by MTHFR have significant associations with the risk of RPL ( Sergi et al, 2015 ; Chen et al, 2016 ; Jusic et al, 2018 ; Perés Wingeyer et al, 2019 ). Rare variants of blood coagulation-associated genes that distort the normal structure or function of the encoded proteins can disrupt the balance mentioned above, cause abnormal hemorrhage in the uterus during pregnancy and result in adverse pregnancy outcomes.…”

Section: Discussionmentioning

confidence: 99%

Exome-Sequencing Identifies Novel Genes Associated with Recurrent Pregnancy Loss in a Chinese Cohort

et al. 2021

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Recurrent pregnancy loss (RPL) is a common reproductive problem affecting around 5% of couples worldwide. At present, about half of RPL cases remained unexplained. Previous studies have suggested an important role for genetic determinants in the etiology of RPL. Here, we performed whole-exome sequencing (WES) analysis on 100 unrelated Han Chinese women with a history of two or more spontaneous abortions. We identified 6736 rare deleterious nonsynonymous variants across all patients. To focus on possible candidate genes, we generated a list of 95 highly relevant genes that were functionally associated with miscarriage according to human and mouse model studies, and found 35 heterozygous variants of 28 RPL-associated genes in 32 patients. Four genes (FOXA2, FGA, F13A1, and KHDC3L) were identified as being strong candidates. The FOXA2 nonsense variant was for the first time reported here in women with RPL. FOXA2 knockdown in HEK-293T cells significantly diminished the mRNA and protein expression levels of LIF, a pivotal factor for maternal receptivity and blastocyst implantation. The other genes, with 29 variants, were involved in angiogenesis, the immune response and inflammation, cell growth and proliferation, which are functionally important processes for implantation and pregnancy. Our study identified several potential causal genetic variants in women with RPL by WES, highlighting the important role of genes controlling coagulation, confirming the pathogenic role of KHDC3L and identifying FOXA2 as a newly identified causal gene in women with RPL.

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Section: Discussionmentioning

confidence: 99%

Exome-Sequencing Identifies Novel Genes Associated with Recurrent Pregnancy Loss in a Chinese Cohort

et al. 2021

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“…Of the 71 included studies, 15 were rated good, [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] 39 were rated fair, and 17 were rated poor. [76][77][78][79][80][81][82][83][84][85][86][87][88][89][90][91][92] Twenty-one studies investigated cases with preeclampsia, 22,24,[34][35][36]45,47,49,54,61,67,[69][70][71][72][73][74][75]86,87,…”

Section: Resultsmentioning

confidence: 99%

“…Table 2 shows extracted data from the 11 studies investigating the association between PAI-1 levels in pregnant women and placenta-mediated pregnancy complications. Of the 71 included studies, 15 were rated good, 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 39 were rated fair, 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 and 17 were rated poor. 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92…”

Section: Resultsmentioning

confidence: 99%

“…Twenty-one studies investigated cases with preeclampsia, 22 24 34 35 36 45 47 49 54 61 67 69 70 71 72 73 74 75 86 87 92 45 studies investigated cases with pregnancy loss described as pregnancy loss, 27 29 31 39 50 51 52 59 60 64 66 68 81 90 91 miscarriage, 23 28 30 38 40 41 42 44 53 55 56 57 58 62 65 76 78 79 88 abortion, 37 43 48 63 77 83 89 fetal loss, 46 80 82 or intrauterine fetal death. 84 One study investigated cases delivering still birth, 33 one study investigated cases delivering newborns meeting the criteria for intrauterine growth restrictions, 26 and three studies investigated cases with various adverse pregnancy outcomes.…”

Section: Resultsmentioning

confidence: 99%

“…The association between PAI-1 genotype and pregnancy loss was investigated in 45 studies. 23 27 28 29 30 31 37 38 39 40 41 42 43 44 46 48 50 51 52 53 55 56 57 58 59 60 62 63 64 65 66 68 76 77 78 79 80 81 82 83 84 88 89 90 91 Pregnancy loss was described as miscarriage, abortion, fetal loss, or intrauterine fetal death. The definition differed across studies according to gestational week and number of pregnancy losses.…”

Section: Resultsmentioning

confidence: 99%

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The Role of Plasminogen Activator Inhibitor Type 1 (PAI-1) in Placenta-Mediated Pregnancy Complications: A Systematic Review

Agersnap

Nissen

Hvas

2022

Semin Thromb Hemost

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Plasminogen activator inhibitor type 1 (PAI-1) is a main inhibitor of fibrinolysis. The PAI-1 gene (SERPINE1) harbors genetic variants with the potential of modifying plasma levels of PAI-1. A delicate balance exists between the coagulation and fibrinolytic system, and changes in PAI-1 have been suggested to compromise establishment of a successful pregnancy. Therefore, this systematic review investigated the association between genetic variants and/or plasma levels of PAI-1 and placenta-mediated pregnancy complications. An extensive literature search was conducted in PubMed, Embase, and Web of Science on the 29th of April 2021. All studies underwent quality rating according to The Study Quality Assessment Tools checklist provided by National Heart, Lung and Blood Institute. A total of 71 studies were included, among which 60 studies investigated PAI-1 genotypes and 11 studies measured PAI-1 plasma levels. In 32 out of 59 studies, no association was found between the PAI-1 4G/5G polymorphism (rs1799768) and placenta-mediated pregnancy complications, which was stated as no significant difference in the genotype distribution comparing women with and without placenta-mediated pregnancy complications or no significantly increased odds of placenta-mediated pregnancy complications carrying the 4G/4G or 4G/5G genotype. Eight out of 11 studies reported significantly higher PAI-1 plasma levels in preeclamptic women than in women without preeclampsia. In conclusion, no clear evidence indicates that PAI-1 polymorphisms are associated with placenta-mediated pregnancy complications, and the possible association between high PAI-1 plasma levels and preeclampsia needs further investigations. Thus, investigation of PAI-1 genotypes and PAI-1 plasma levels does not currently seem to have a place in daily clinical practice managing placenta-mediated pregnancy complications.

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Determining the association of thrombophilic gene polymorphisms with recurrent pregnancy loss in Iranian women

Khorshidi

Hajizadeh

Choobineh

et al. 2020

Gynecological Endocrinology

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Inherited thrombophilia and pregnancy loss. Study of an Argentinian cohort

Cited by 8 publications

References 28 publications

Exome-Sequencing Identifies Novel Genes Associated with Recurrent Pregnancy Loss in a Chinese Cohort

Exome-Sequencing Identifies Novel Genes Associated with Recurrent Pregnancy Loss in a Chinese Cohort

The Role of Plasminogen Activator Inhibitor Type 1 (PAI-1) in Placenta-Mediated Pregnancy Complications: A Systematic Review

Determining the association of thrombophilic gene polymorphisms with recurrent pregnancy loss in Iranian women

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