The Prevalence Of Specific Gene Polymorphisms Related To Thrombophilia In Egyptian Women With Recurrent Pregnancy Loss.
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ABSTRACT: Background
Despite the enhanced progress in identifying a number of leading causes to fetal miscarriage, still some women suffer from recurrent pregnancy loss (RPL) for unknown cause. A hidden genetic influence of coexisting hereditary thrombophilia was assumed to have a role.Aim
The aim was to investigate the association between unexplained RPL and thrombophilic gene variants of angiotensin I-converting enzyme (ACE) (rs4646994) and β-fibrinogen (rs1800790) genes.Settings and design
The present case-control study was conducted on unexplained RPL in eighty women and eighty matched controls with no history of previous pregnancy loss.Materials and methods
Analysis of extracted DNA was performed using polymerase chain reaction-restriction fragment length polymorphism method.Statistical analysis
The frequency of genotypes and alleles was compared between groups using Chi-square test or Fisher's exact test. Risk assessment was made by odds ratio (OR) at a 95% confidence interval (CI).Results
Women with RPL group had higher frequency of DD than controls (47.5%, 31.25%, respectively, P = 0.086). D allele frequency was 0.67 and 0.54 in the control (P = 0.022). D allele carriers were at higher risk of RPL than the control as OR was 1.694 at 95% CI from 1.08 to 2.67. There was no association between the rs1800790 variant of β-fibrinogen gene and RPL.Conclusion
Females who are carriers for D allele of ACE I/D gene polymorphism are more liable to suffer from RPL. Screening for hereditary thrombophilia in females who are planning to conceive and have a history of RPL of unidentified cause is of great value to provide proper management and genetic counseling to high-risk couples.
SUBMITTER: Issa NM
PROVIDER: S-EPMC8057147 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The aim of this prospective cohort study was to determine whether women with recurrent pregnancy loss (RPL) have an increased risk of pregnancy complications compared to normal pregnant women. A total of 1092 singleton pregnancies were followed, 431 in women with RPL and 661 in normal healthy women. The prevalence of the following complications was observed: threatened miscarriage, miscarriage, cervical insufficiency, chromosomal/genetic abnormalities, fetal anomalies, oligohydramnios, polyhydramnios, fetal growth restriction, intrauterine fetal death, gestational diabetes mellitus (GDM), preeclampsia, placenta previa, abruptio placentae, pregnancy-related liver disorders, and preterm premature rupture of the membranes. The odds ratio and 95% CI for each pregnancy complication considered were determined by comparing women with RPL and normal healthy women. Women with RPL had an overall rate of pregnancy complications higher than normal women (OR = 4.37; 95% CI: 3.353-5.714; p < 0.0001). Their risk was increased for nearly all the conditions considered. They also had an increased risk of multiple concomitant pregnancy complications (OR = 4.64; 95% CI: 3.10-6.94, p < 0.0001). Considering only women with RPL, women with ≥3 losses had a higher risk of pregnancy complications than women with two losses (OR = 1.269; 95% CI: 1.112-2.386, p < 0.02). No differences were found in the overall risk of pregnancy complications according to the type, explained or unexplained, of RPL. Women with secondary RPL had an increased risk of GDM than women with primary RPL. Pregnancy in women with RPL should be considered at high risk.
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Project description:BackgroundThrombophilia is a group of disorders that result in a blood hypercoagulable state and induce thrombosis, which was found widely existed in recurrent pregnancy loss (RPL). More and more research about thrombophilia has been conducted but the association between thrombophilia and RPL remains uncertain. Thus, it's necessary to combine relevant literature to find the research hotspots and analyze the internal link between different study points, and then predict the development trend in RPL with thrombophilia.MethodsRelevant articles between 1970 and 2022 were obtained from the Web of Science (WoS) database. Software VOSviewer and CiteSpace were used to perform the analysis and conduct visualization of scientific productivity and emerging trends.ResultsSeven hundred twenty-five articles published in recent 30 years by 3205 authors from 1139 organizations and 68 countries were analyzed. 37authors, 38 countries, and 53 organizations published papers ≥5. The United States was the most productive country and Univ Amsterdam was the most productive institution. Journal thrombosis and haemostasis had the most total citations. In keyword and clusters, factor-v-Leiden, inherited thrombophilia, activated protein-c, low-dose aspirin, molecular-weigh heparin, polymorphism had high-frequency focus on its etiology, diagnostics, and therapeutics. The strongest keyword bursts showed the research hotspots changed over time.ConclusionsThere could be differences in the clinical relevance of different type of thrombophilia, as well as single and multiple thrombophilic factors. Anticoagulation and immunotherapy are currently the main treatment options. More clinical trials and basic research are expected and we should attach more attention to the whole management of in-vitro fertilization in the future.
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Project description:Pregnancy loss is the most common complication of human pregnancy. Recurrent early pregnancy loss (REPL) has multiple etiologies, including endometrial dysregulation leading to “suboptimal” implantation. Although the implantation process is tightly regulated in Eutherian (placental) mammals, the molecular factors contributing to dysregulated endometrial gene expression patterns in women with REPL are largely unknown. We hypothesized that genes that gained novel expression in the endometria of mammals that evolved in the Eutherian stemlineage, coincident with the evolution of pregnancy, are likely essential for establishment and maintenance of normal pregnancy and are, therefore, good candidates for genes whose expression may be dysregulated in disorders such as REPL. To test this hypothesis, we took an evolutionary forward genomics approach to characterize gene expression profiles of midsecretory endometria from women with REPL associated with abnormal endometria based either on histology or molecular expression of cyclin E. We identified 58 genes that were differentially expressed (P<0.001) between women with out-of-phase histological dating vs normal histology, and 81 genes that were differentially expressed (P<0.001) between women with abnormally elevated cyclin E levels vs normal cyclin E. Remarkably, genes that were recruited into endometrial expression during the evolution of pregnancy in Eutherian mammals were significantly enriched for dysregulated genes (P=0.002 for histology, P=0.021 for cyclin E), as well as for immune and signaling pathways with essential roles in endometrial biology. Thus, our novel evolutionary-based forward genomics approach identified genes whose dysregulation during the mid-secretory phase likely contributes to the molecular etiologies of recurrent early pregnancy loss. Total RNA obtained from mid luteal phase endometrium (two replicates per biopsy) from women with recurrent early pregnancy loss (REPL). Endometrial gene expression levels were compared 1) between women with out-of-phase (n=10) and normal histological dating (n=22), 2) between women with abnormally elevated (n=9) and normal (n=23) cyclin E levels. For 5 additional women with abnormally high cyclin E levels, biopsy samples were collected before and after progesterone treatment to investigate the gene expression profiles in response to progesterone.
2014-12-06 | E-GEOD-63901 | biostudies-arrayexpress
Project description:Pregnancy loss is the most common complication of human pregnancy. Recurrent early pregnancy loss (REPL) has multiple etiologies, including endometrial dysregulation leading to “suboptimal” implantation. Although the implantation process is tightly regulated in Eutherian (placental) mammals, the molecular factors contributing to dysregulated endometrial gene expression patterns in women with REPL are largely unknown. We hypothesized that genes that gained novel expression in the endometria of mammals that evolved in the Eutherian stemlineage, coincident with the evolution of pregnancy, are likely essential for establishment and maintenance of normal pregnancy and are, therefore, good candidates for genes whose expression may be dysregulated in disorders such as REPL. To test this hypothesis, we took an evolutionary forward genomics approach to characterize gene expression profiles of midsecretory endometria from women with REPL associated with abnormal endometria based either on histology or molecular expression of cyclin E. We identified 58 genes that were differentially expressed (P<0.001) between women with out-of-phase histological dating vs normal histology, and 81 genes that were differentially expressed (P<0.001) between women with abnormally elevated cyclin E levels vs normal cyclin E. Remarkably, genes that were recruited into endometrial expression during the evolution of pregnancy in Eutherian mammals were significantly enriched for dysregulated genes (P=0.002 for histology, P=0.021 for cyclin E), as well as for immune and signaling pathways with essential roles in endometrial biology. Thus, our novel evolutionary-based forward genomics approach identified genes whose dysregulation during the mid-secretory phase likely contributes to the molecular etiologies of recurrent early pregnancy loss.
2014-12-06 | GSE63901 | GEO
Project description:Uterine radial artery resistance index (URa-RI) by Doppler ultrasound may reflect the changes in the uteroplacental circulation and be associated with adverse events in early pregnancy. Recurrent pregnancy losses (RPL) are associated with thrombophilia, and anticoagulation treatment with low molecular weight heparin improves pregnancy outcome in women with RPL and thrombophilia. A retrospective cohort study was conducted in 139 pregnant women with 3 or more RPL and thrombophilia. The relationship between pregnancy outcome and dynamic changes of URa-RI was analyzed in 116 women who delivered a liveborn infant and 23 who miscarried the index pregnancy. Patients were on preconception low molecular weight heparin, low-dose aspirin (81mg per day), and prednisone treatment. URa-RI was measured during periovulation time, at the time of positive pregnancy test, and then repeated every two weeks until 32-week gestation or the time of miscarriage. The URa-RI at 8-week gestation was significantly higher in women who miscarried the index pregnancy than those who delivered alive born infant (0.51±0.08 vs. 0.42±0.03, P<0.001). Receiver operating characteristic curve analysis demonstrated that URa-RI of 8 wk gestation effectively distinguished women who miscarried from those who had a live birth with an area under the curve of 82.6% (95% CI 69.01-97.17). After adjusting for covariates including age, BMI, and number of miscarriages, multiple logistic regression models showed that each 0.1 unit increase of URa-RI of 8 wk gestation was associated with 18.70-point increase in the risk of miscarriage (OR19.70, 95%CI 4.26-91.1, P<0.001), and women with an URa-RI?0.45 had an OR of 49.48 (95% CI 8.01-307.95; P<0.001) for miscarriage compared to those who had URa-RI<0.45. In women with RPL and inherited thrombophilia, increased URa-RI at 8-week gestation was associated with spontaneous abortion independent of other risk factors while they were on anticoagulation treatment.
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Project description:PurposeRecurrent pregnancy loss (RPL) is defined as the occurrence of two or more miscarriages before the 20th week of pregnancy. T helper17 cells are a novel subset of T cells, which secrete IL (Interleukin)-17 and are known to be involved in inflammation, autoimmunity and rejection of non-self tissues. Herein, we studied the association between IL-17A rs2275913 and IL-17F rs763780 gene polymorphisms with RPL in Iranian women.MethodsA case-controlled study was performed on two groups consisting of 85 healthy women with at least one delivery and 85 women with the history of two or more RPLs. The frequency of IL-17A rs2275913 and IL-17 F rs763780 polymorphisms were determined by PCR-RFLP.ResultsIn the RPL group, the genotypes frequencies of rs2275913 polymorphism were GG (8.2 %), AG (30.6 %), and AA (61.2 %) and in the control group, were GG (3.5 %), AG (42.4 %) and AA (54.1 %). Statistical analysis showed no significant difference between the genotypes of AA, AG and GG in the two groups (p = 0.1). The genotypes frequencies of rs763780 polymorphism were TT (43.5 %), TC (49.4 %) and CC (7.1 %) in the RPL group; whereas the frequencies were TT (25.9 %), TC (70.6 %) and CC (3.5 %) in the control group. Statistical analysis revealed a significant difference in the TT, TC, and CC genotypes frequencies between the case and the control groups (p = 0.01).ConclusionsOur findings indicate that IL-17F polymorphism, rs763780, might be associated with a high risk of RPL in Iranian women.
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Project description:Background: Structural chromosome abnormality (SCA) is an important cause of human diseases, including recurrent pregnancy loss (RPL). DNA double-strand breaks (DSBs) repair-related genes play critical roles in SCA. The present study aims to investigate the potential contribution of DSBs repair-related gene polymorphisms to SCA. Methods: Fifty-four affected RPL individuals with SCA, 88 affected RPL individuals without SCA, and 84 controls were analyzed. Targeted whole-exome sequencing (WES) was used for screening single nucleotide polymorphisms in six DSBs repair-related genes (EP300, XRCC6, LIG4, XRCC4, PRKDC, and DCLRE1C), and validation was performed by Sanger sequencing. Finally, we detected the frequency of radiation-induced chromosome translocations in no SCA samples with significant polymorphisms by fluorescence in situ hybridization (FISH). Results: A total of 35 polymorphisms have been identified and confirmed. Frequencies of EP300 rs20551, XRCC6 rs132788, and LIG4 rs1805388 were significantly different between SCA RPL and no SCA RPL (p = 0.030, 0.031, and 0.040 respectively). Frequencies of those three gene polymorphisms between SCA RPL and controls also were significantly different (p = 0.017, 0.028, and 0.029 respectively). Moreover, the frequency of the G allele at rs20551 locus, the T allele at rs132788 locus and the A allele at rs1805388 locus was significantly higher in SCA RPL than no SCA RPL (OR = 3.227, p = 0.005; OR = 1.978, p = 0.008 and OR = 1.769, p = 0.036 respectively) and controls (OR = 7.130, p = 0.000; OR = 2.157, p = 0.004; OR = 2.397, p = 0.003 respectively). Additionally, the frequency of radiation-induced translocation in no SCA samples with rs20551, rs132788 or rs1805388 was significantly higher compared with the wild type samples (p = 0.015, 0.012, and 0.007 respectively). Conclusion: Our results suggest that rs20551, rs132788, and rs1805388 might be associated with the risk of SCA. Larger scales of genetic variations studies and functional experiments are necessary to further confirm these findings.
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Project description:An Argonaute (AGO) protein within the RNA-induced silencing complex binds a microRNA, permitting the target mRNA to be silenced. We hypothesized that variations in AGO genes had the possibility including affected the miRNA function and associated with recurrent pregnancy loss (RPL) susceptibility. Especially, we were chosen the AGO1 (rs595961, rs636832) and AGO2 (rs2292779, rs4961280) polymorphisms because of those polymorphisms have already reported in other diseases excluding the RPL. Here, we conducted a case-control study (385 RPL patients and 246 controls) to evaluate the association of four polymorphisms with RPL. We found that the AGO1 rs595961 AA genotype, recessive model (P = 0.039; P = 0.043, respectively), the AGO1 rs636832 GG genotype, and recessive model (P = 0.037; P = 0.016, respectively) were associated with RPL in women who had had four or more consecutive pregnancy losses. The patients with the AGO1 rs636832 GG genotypes had greater platelet counts (P = 0.023), while the patients with the AGO2 rs4961280 CA genotypes had less homocysteine (P = 0.027). Based on these results, we propose that genetic variations with respect to the AGO1 and AGO2 genotypes are associated with risk for RPL, and might serve as useful biomarkers for the prognosis of RPL.
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