Risk Of Recurrent Miscarriage Research Articles

Association between the rs2288947 polymorphism of the lncRNA TINCR gene and the risk of recurrent miscarriage in a Southern Chinese population.

Studies have shown that many genes that regulate cell migration are associated with susceptibility to recurrent miscarriage. Terminal differentiation‐induced non‐coding RNA (TINCR) regulates the migration and invasion of a variety of tumor cells and is associated with susceptibility to various diseases. However, whether the lncRNA TINCR polymorphism is associated with susceptibility to recurrent miscarriage is unclear. Therefore, we investigated the relationship between the rs2288947 A > G polymorphism of the lncRNA TINCR and susceptibility to recurrent abortion. We recruited 248 recurrent spontaneous abortion patients and 392 healthy control subjects from the Southern Chinese population and used the TaqMan method for genotyping. There was no evidence that this polymorphism is associated with recurrent miscarriage (AG vs AA: adjusted OR = 0.904, 95% CI = 0.647‐1.264, P = 0.5552; GG and AA: adjusted OR = 0.871, 95% CI = 0.475‐1.597, P = 0.6542; dominant model: AG/GG vs AA: adjusted OR = 0.898, 95% CI = 0.653‐1.236, P = 0.5101; and recessive model: GG vs AA/AG: adjusted OR = 0.910, 95% CI = 0.505‐1.639, P = 0.7527). The stratified analysis also showed no significant associations. This study suggests that the rs2288947 A > G polymorphism of the lncRNA TINCR may not be associated with recurrent miscarriage in a Southern Chinese population. A larger multicenter study is needed to confirm our conclusions.

The lncRNA CCAT2 rs6983267 G allele is associated with decreased susceptibility to recurrent miscarriage.

Genetics might play various roles in susceptibility to recurrent miscarriage, and previous studies suggest that some gene polymorphisms might be associated with abortion and breast cancer onset. Colon cancer-associated transcript 2 (CCAT2) is a novel long noncoding RNA (lncRNA) transcript that might be correlated with susceptibility to multiple cancers, including breast cancer. However, whether lncRNA CCAT2 polymorphisms are related to susceptibility to recurrent miscarriage is unclear. We genotyped two lncRNA CCAT2 polymorphisms (rs6983267 and rs3843549) in 248patients with recurrent miscarriage and 392 controls through a TaqMan real-time polymerase chain reaction assay, and the strength of each association was evaluated via 95% confidence intervals (CIs) and odds ratios (ORs). Our results showed that the rs6983267 G allele in lncRNA CCAT2 was associated with decreased susceptibility to recurrent miscarriage (TG vs. TT: adjusted OR = 0.603; 95% CI = 0.420-0.866; p = 0.0062; GG/TG vs. TT: adjusted OR = 0.620; 95% CI = 0.441-0.873; p = 0.0061). The combined analysis of the two protective polymorphisms (rs3843549 AA and rs6983267 TG/GG) revealed that individuals with two unfavorable alleles exhibited a lower risk of recurrent miscarriage than those with no or only one unfavorable allele (adjusted OR = 0.531; 95% CI = 0.382-0.739). Moreover, the decreased risk associated with the two protective alleles was most obvious in women aged less than 35 years (OR = 0.551; 95% CI = 0.378-0.8803; p = 0.0019) and in women with two to three miscarriages (adjusted OR = 0.466; 95% CI = 0.318-0.683; p < 0.0001). In conclusion, our study indicates that the rs6983267G allele might contribute to a decreased risk of recurrent miscarriage in the South Chinese population.

The prevalence of combined vascular endothelial growth factor, endothelial nitric oxide synthase and thrombin-activatable fibrinolysis inhibitor genetic polymorphisms among Egyptian patients with recurrent spontaneous abortion.

As angiogenesis is an essential step for chorionic villi formation. Vascular endothelial growth factor (VEGF) is essential for endothelial cell proliferation. Endothelial nitric oxide synthase (eNOS) is a powerful playmaker in hypoxia-induced angiogenesis. Thrombin-activatable fibrinolysis inhibitor (TAFI) regulates both fibrinolysis and inflammation. Genetic alterations of these factors may lead to recurrent spontaneous abortion (RSA). We aimed to investigate the combined genetic variants of VEGF G-1154A and two eNOS genetic variants: T-786C promoter region and intron 4 variable number of tandom repeats in addition to TAFI C-1040T among RSA patients. The study included 50 patients with RSA and 50 healthy controls. Polymerase chain reaction and restriction fragment length polymorphism were used for genotyping. Both genetic alterations of eNOS confirmed at least a sixfold increase of RSA risk. Interestingly, they were associated with TAFI C-1040Tgenetic variant in 21 patients, eight of them had both studied eNOS genetic alterations and TAFI C-1040Tgenetic variant, while each eNOS genetic variant associated with TAFI C-1040Tconfirmed an almost one and half fold increase risk of RSA. These findings highlighted the role of eNOS and nitric oxide metabolism in RSA and opened the gate to investigate the interaction of vasoconstrictive and fibrinolytic inhibitor systems.

The lncRNA MALAT1 rs619586 G Variant Confers Decreased Susceptibility to Recurrent Miscarriage.

Cardiovascula disease and recurrent miscarriage have shared risk factors, and some cardiovascular disease-related candidate genes have been confirmed to be associated with recurrent miscarriage. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) that is considered to be associated with susceptibility to cardiovascular disease. However, whether lncRNA MALAT1 polymorphisms are related to recurrent miscarriage susceptibility is unclear. We genotyped three lncRNA MALAT1 polymorphisms (rs591291, rs619586, and rs3200401) in 284 patients and 392 controls using TaqMan methods. Logistic regression was used to evaluate the odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for age. Our results showed that the rs619586 G variant had protective effects against recurrent miscarriage (AG vs. AA: adjusted OR = 0.670, 95% CI = 0.457–0.982, p = 0.040; GG vs. AA: adjusted OR = 0.278, 95% CI = 0.079–0.975, p = 0.046; GG/AG vs. AA adjusted OR = 0.621, 95% CI = 0.429–0.900, p = 0.012). In a combined analyses of protective genotypes, with regard to the three single nucleotide polymorphisms (SNPs), we found that individuals with two or three protective genotypes exhibited a significantly lower risk of recurrent miscarriage than those with no or only one protective genotype (adjusted OR = 0.369, 95% CI = 0.199–0.684, p = 0.002). Moreover, the decrease in recurrent miscarriage risk with two or three protective genotypes was most pronounced in women less than 35 years of age (OR = 0.290, 95% CI = 0.142–0.589, p < 0.001) and in women with 2–3 miscarriages (adjusted OR = 0.270, 95% CI = 0.126–0.580, p < 0.001). In conclusion, our study suggests that the rs619586 G variant may have potential protective effects conferring a decreased risk of recurrent miscarriage in the southern Chinese population.

The association of polymorphisms in promoter region of MMP2 and MMP9 with recurrent spontaneous abortion risk in Chinese population.

This study aimed to reveal the genetic association between polymorphisms in promoter region of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) and the risk of recurrent spontaneous abortion (RSA) in Chinese population.A total of 129 RSA patients and 116 relative controls were selected and the genotyping of polymorphism was conducted by polymerase chain reaction with sequencing. Genotype distribution of polymorphism in the control group was tested the status of Hardy–Weinberg equilibrium and then, genotype frequencies were compared between the case and control groups by chi-squared test. Odds ratio (OR) with the corresponding 95% confidence interval (95% CI) was computed to express the risk of RSA caused by polymorphism. Moreover, the linkage disequilibrium of polymorphisms in MMP2 was analyzed by Haploview software.CT genotype and T allele of rs243865 in MMP2 were significantly associated with the increased susceptibility to RSA in Chinese population (CT vs. CC: OR = 1.926, 95% CI = 1.101–3.368; T vs. C: OR = 1.751, 95% CI = 1.146–2.676). Similarly, CT genotype carriers of rs3918242 in MMP9 were obviously more in RSA patients than that of the controls (P = .037), which indicated it was associated with the risk of RSA occurrence (OR = 1.760, 95% CI = 1.034–2.995). So was T allele in RSA development (OR = 1.595, 95% CI = 1.061–2.398). Haplotypes C-T and T-C were also the risk factors of RSA (OR = 1.673, 95% CI = 1.103–2.536; OR = 2.171, 95% CI = 1.372–2.436).MMP2 rs243865 and MMP9 rs3918242 polymorphisms are significantly associated with the risk of RSA in Chinese population.

Correlation between CTLA4 genetic polymorphisms, its serum protein level and the susceptibility to recurrent spontaneous abortion: A case-control study.

Present study was aimed to detect the influence of cytotoxic T-lymphocyte associated protein 4 (CTLA4) gene polymorphisms for the risk of recurrent spontaneous abortion (RSA), as well as the serum level of CTLA4 protein in RSA patients.One hundred thirty-three RSA patients and 146 healthy persons were recruited in this case–control study. PCR-RFLP was used to genotype the CTLA4 gene polymorphisms both in case and control groups. Serum level of CTLA4 was detected by ELISA kit. Quantitative variables were compared by t test or Mann–Whitney U test between groups. Qualitative variables were evaluated by χ2 test or Fisher exact test. Association strength was expressed by odds ratios (ORs) and 95% confidence intervals (95% CIs).G allele of rs4553808 (P = .027, OR = 0.570, 95% CI = 0.345–0.942) and T allele of rs5742909 (P = .027, OR = 0.570, 95% CI = 0.345–0.942) were distinctly associated with reduced susceptibility of RSA. Distinctly negative association has been discovered between rs231775 AA genotype and RSA susceptibility (P = .040, OR = 0.427, 95% CI = 0.188–0.973). CTLA4 protein had significantly higher serum level in RSA patients than in healthy controls (P = .028). In RSA patients, AA genotype carriers had higher CTLA4 serum level than that GG genotype carriers (17.83 ± 6.35 ng/mL vs 10.41 ± 7.28 ng/mL, P = .039).Minor alleles of CTLA4 polymorphisms might inhibit the RSA susceptibility via upregulated the protein expression level.

The relationship between MTHFR polymorphisms and abortion in Iranian women

BackgroundRecurrent spontaneous abortion (RSA) is a significant obstetrical complication during pregnancy. Two common polymorphisms (C677T and A1298C) of the methylenetetrahydrofolate reductase (MTHFR) gene are risk factors for RSA. This study was performed to determine the effect of C677T and A1298C polymorphisms in RSA. The true relationship between these two mutations and risk of recurrent spontaneous abortion is unknown, and it is unclear if women with these mutations should be given anticoagulants during pregnancy. Materials and methodsIn this prospective and experimental study, one hundred and fifty three individuals were referred with clinical findings that included recurrent spontaneous abortions minimum of 2 and maximum of 5. Total genomic DNA was isolated from peripheral blood samples. To determine the frequency of the two common C677T and A1298C MTHFR gene polymorphisms in the patients, we used PCR-restriction fragment length polymorphism method. ResultsThe frequency of Heterozygous and homozygous C677T polymorphisms were 18.13% and 13.1% respectively. The frequency of Heterozygous and homozygous A1298C polymorphisms were 18.3% and 15.7% respectively. The frequency of Heterozygous C677T and A1298C polymorphisms were 26.8% and wild-type individuals were 7.8%. All female subjects who had heterozygous or homozygous C677T and A1298C polymorphisms with recurrent RSA were followed and those who received appropriate anti-coagulant therapy resulted in successful pregnancy. ConclusionIn present study, we provided witness to support the relationship between MTHFR C677T and A1298C polymorphisms and recurrent spontaneous abortion. Also, we suggest that anticoagulation therapy of these patients during pregnancy could lead to a successful pregnancy outcome.

WNT7A (rs104893832) polymorphism increases the risk of recurrent spontaneous abortion in Iranian women

BACKGROUNDRecurrent spontaneous abortion is defined as the occurrence of three or more clinical miscarriages in one woman. Several factors, including genetics and environmental factors, are involved in this kind of infertility, in which WNT7A (rs104893832) polymorphism plays a major role. The aim of the present study was to determine the association between a common polymorphism of WNT7A (rs104893832) with recurrent spontaneous abortion in females. METHODSIn the present case-control study, the WNT7A (rs104893832) polymorphism was investigated in 70 women with recurrent spontaneous abortion as cases and 100 women with at least one child and no history of infertility or abortion as controls. Polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) was used to investigate the WNT7A (rs104893832) polymorphism in both case and control groups. The data were subsequently analyzed using the chi-square and logistic regression tests by SPSS software (version 18.0). RESULTSA significant association was found between the WNT7A (rs104893832) polymorphism and recurrent spontaneous abortion (OR=25.00, 95% CI=5.52-157.09; p&lt;0.0001). Our finding showed that G allele frequency in women with recurrent spontaneous abortion was significantly different compared to the control group. (OR=6.42, 95% CI=2.82-15.16; p&lt;0.0001).Therefore, genetic variation in WNT7A (rs104893832) polymorphism may play a role in recurrent spontaneous abortion. ConclusionThis study revealed that WNT7A (rs104893832) polymorphism increased the risk of recurrent spontaneous abortion. Knowledge of these mutations and polymorphisms can provide an insight into the prognosis for individual patients. Therefore, further studies are necessary to establish the association of WNT7A (rs104893832) polymorphism with recurrent spontaneous abortion in a larger population.

Association of Estrogen Receptor 1 Genetic Polymorphisms with Recurrent Spontaneous Abortion Risk.

Background:Estrogen is one of the most important reproductive steroidal hormones and plays a critical role in the maintenance of pregnancy, and its function is mediated by estrogen receptor 1(ESR1). The polymorphisms of ESR1 were involved in recurrent spontaneous abortion (RSA); however, the association between ESR1 polymorphisms and RSA remains controversial. The present meta-analysis was aimed to clarify the association between ESR1 PvuII (-397C/T, rs2234693) and XbaI (-351A/G, rs9340799) polymorphisms and the risk of RSA.Methods:All the included articles were retrieved from PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Med Online Database up to January 3, 2018. Data were processed in the Stata 12.0 software. The odds ratios (OR s) and 95% confidence intervals (95% CIs) were calculated using fixed-effects models (FEM)/random-effects models (REM).Results:Seven case–control studies with 836 cases and 1164 controls were included in the study. Generally, the ESR1 polymorphisms were not associated with RSA in any of the genetic analysis models. However, it was found that as rs9340799 polymorphism was related to increased risk of RSA in non-Asian group in the homozygous genetic model (OR = 2.40, 95% CI = 1.05–5.50, P = 0.039). Moreover, in Asian group, rs9340799 polymorphism was found to be related to decreased RSA risk in both the heterozygous model (OR = 0.53, 95% CI = 0.33–0.85, P = 0.009) and the dominant genetic model (OR = 0.55, 95% CI = 0.30–0.98, P = 0.042).Conclusions:Generally, there was no significant association between the polymorphisms of ESR1 and the risk of RSA. However, subgroup analysis indicated that ESR1 rs9340799 polymorphism was related to increased RSA risk in the non-Asian group while associated with decreased RSA risk in Asian group.

Evaluation of transcobalamin II rs1801198 and transcobalamin II receptor rs2336573 gene polymorphisms in recurrent spontaneous abortion

It has been proposed that transcobalamin 2 (TCN2) and the transcobalamin 2 receptor (TCN2R) are associated with idiopathic recurrent spontaneous abortion (RSA). The aim of the present study was to investigate the impact of TCN2 rs1801198 and TCN2R rs2336573 polymorphism on RSA in a sample of Iranian population. This case-control study was done on 92 RSA patients and 93 normal, fertile women. Genotyping of the TCN2 rs1801198 and TCN2R rs2336573 variants was done by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The findings showed no significant association between the TCN2 rs1801198 and TCN2R rs2336573 polymorphisms and the risk/protection of RSA. Our results did not support an association between the TCN2 polymorphism and the risk of RSA in a sample of southeast Iranian population. Larger studies with different ethnicities are needed to evaluate the possible impact of TCN2 and TCN2R polymorphisms on the pathogenesis of RSA.Impact statementWhat is already known on this subject? Recurrent spontaneous abortion (RSA), a multifactorial condition, is one of the most common complications of pregnancy. It has been proposed that genetic polymorphisms play a role in the pathogenesis of RSA. Few studies have examined the association between TNC2 and TCN2R polymorphisms and the RSA risk and the findings were inconsistent. The aim of the current study was to determine the possible association between the TCN2 rs1801198 and TCN2R rs2336573 polymorphisms and the RSA in a sample of the southeast Iranian population.What do the results of the study add? The findings of the present case-control study did not support an association between the TCN2 rs1801198 and TCN2R rs2336573 polymorphisms and the risk of RSA in a sample of the Iranian population.What are the implications of these findings for clinical practice and future research? The findings of this study may provide a basis for future studies with larger sample sizes and different ethnicities on the role of TCN2 and TCN2R polymorphisms in the pathogenesis of RSA.

The synergic effects of CTLA-4/Foxp3-related genotypes and chromosomal aberrations on the risk of recurrent spontaneous abortion among a Chinese Han population

The current study was aimed to investigate the association of CLTA-4/Foxp3 polymorphisms and chromosomal abnormalities with recurrent spontaneous abortion (RSA) risk in a Chinese Han population. Altogether, 1284 RSA women and 1046 women with normal pregnancy were incorporated in this study. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was implemented to genotype the single-nucleotide polymorphisms (SNPs) located within CTLA4 and Foxp3. Moreover, the cytogenetic diagnosis was performed in line with the standards of G banding karyotype. As a consequence, rs231775 and rs3087243 of CTLA4, as well as rs2232365 and rs2232368 of Foxp3, all appeared to modify the risk of RSA. Besides, significant differences were found between the ratio of structural abnormality and that of numerical abnormality (P < 0.038), and chromosome abnormality was associated with higher miscarriage frequency (>3) than normal karyotypes. Of note, the synergic effects of the genotypes and chromosomal abnormality all tallied with the sub-multiplication model (ORchromosome × ORSNP > ORchromosome+SNP), while rs2232365 GG and chromosomal aberration impacted the RSA risk in a super-multiplicative way that ORchromosome × ORSNP < ORchromosome+SNP. In conclusion, susceptibility to RSA was subject to the synthetic regulation of chromosomal aberrations and genetic mutations within CLTA-4 and Foxp3, suggesting that the conduction of karyotype analysis and genetic detection for RSA patients could effectively guide effective RSA counseling and sound child rearing.

The -2549 insertion/deletion polymorphism in the promoter region of VEGF is associated with the risk of recurrent spontaneous abortion.

Recurrent spontaneous abortion (RSA) is a common health problem affecting women of reproductive age. Altered expression of vascular endothelial growth factor (VEGF) has been associated with spontaneous abortion. The present case-control study aimed to evaluate the impact of the 18-bp insertion/deletion (ins/del) polymorphism (rs35569394) in the promoter region of the VEGF gene on idiopathic RSA. Genomic DNA from 93 patients with RSA and 93 healthy fertile women of southeastern Iran was isolated using the salting-out method. Genotyping of the rs35569394 variant was performed by a polymerase chain reaction (PCR) method. The findings indicated that the VEGF 18-bp ins/del variant significantly increased the risk of RSA under codominant (ins/ins vs. del/del; OR=2.85, 95% CI=1.31-6.22, P=0.019), dominant (del/ins+ins/ins vs. del/del; OR=2.19, 95% CI=1.20-4.01, P=0.015) and allelic (ins vs. del; OR=1.90, 95% CI=1.25-2.88, P=0.003) inheritance models. In summary, the findings propose a significant association between the VEGF 18-bp ins/del polymorphism and risk of RSA in a sample of the southeast Iranian population. Further studies on larger sample sizes and different ethnicities are required to validate the present findings.

Polymorphisms of F2, PROC, PROZ, and F13A1 Genes are Associated With Recurrent Spontaneous Abortion in Chinese Han Women.

Mutations of hemostasis/coagulation-related genes have been speculated to cause recurrent spontaneous abortion (RSA). This study investigated the genetic association between the polymorphisms of factor V (F5), factor II (F2), antithrombin (SERPINC1), protein C (PROC), protein S (PROS1), protein Z (PROZ), factor XIII (F13A1), and carboxypeptidase B2 (CPB2) genes and RSA. The 426 patients with RSA and 444 controls were recruited in this study, and single-nucleotide polymorphisms (SNPs) were analyzed by using SNPscan technology. Genotype and allele frequencies of rs3136520 in F2, rs3024731 in PROZ, and rs1050782 in F13A1 showed statistically significant differences between the 2 groups. TT genotype of rs3136520 (P = .031, odds ratio [OR] = 0.986, 95% confidence interval [CI] = 0.976-0.997) and AA genotype of rs2069906 in PROC (P = .021, OR = 0.114, 95% CI = 0.014-0.902) in their recessive models and AG + GG variants of rs1050782 (P = .007, OR = 0.681, 95% CI = 0.516-0.899) in the dominant model might be associated with the reduced risk of RSA. AT + TT variants of rs3024731 (P = .010, OR = 1.479, 95% CI = 1.098-1.994) may increase disease susceptibility in dominant model. Haplotype analysis of rs3024731 and rs3024735 in PROZ displayed that the AA and TG haplotype were inclined to decrease and increase the risk of RSA, respectively. These results suggested that rs3136520, rs2069906, rs3024731, and rs1050782 may have a significant association with the genetic susceptibility of RSA in Chinese Han women.

Level of placental trophoblastic KISS1 protein is associated with high risk of recurrent spontaneous abortion in Iraqi women

Introduction: Recurrent pregnancy loss is the syndrome that causes repeated miscarriage and/or stillbirth impairing the ability to have a live birth. More from research interest has been focused on the association studies between different factors and recurrent spontaneous abortion. The aim of this study was examine the role of alteration in levels of KISS1protein and in recurrent spontaneous abortion (RSA). Methods: Level of KISS1 protein was detected by immunohistochemical examinations in samples from placenta and measurement the levels of Follicle stimulating hormone (FSH) , Luteinizing hormone (LH) by using Enzyme linked Fluorescent Assay (ElFA) technique of groups I (women pregnant were normal delivered pregnancy at delivery in the third trimester (n=15); II refer to normal pregnant in first trimester (n = 15) (I ;II control group)., III represented aborted women for the first time during the first trimester (n = 15.( and group (IV): (30) represented repeated aborted women during the first trimester Results: Finding from this study revealed that the level of the protein was high in abortion groups and increased levels of LH and FSH as well. Conclusion: Kisspeptine is implicated in RSA through inhibition of normal placentation and indirectly through stimulation of LH and FSH secretion.

The Relation between Serum Homocystiene Level and Recurrent Abortion in Egyptian Women

Background: Early pregnancy loss is defined as the termination of pregnancy before 20 weeks' gestation or with a fetal weight of <500 g. Of those that are recognized, 15-20% result in spontaneous abortions (SABs) or ectopic pregnancies. Approximately 5% of couples trying to conceive have two consecutive miscarriages, and approximately 1% of couples have three or more consecutive early pregnancy loss. Increased levels of homocysteine may be due to inadequate dietary intake of folate and vitamin B12 and inherited defects within the methionine-hmocysteine pathway such as MTHFR c677T gene polymorphism. Hyperhomocysteinemia is associated with the syndromes of repeated miscarriage. Objective: The aim of the current study is to estimate the serum levels of Homocystine and vitamin B12 and their relation to prevalence of recurrent spontaneous abortion in pregnancies with history of recurrent miscarriage. Subjects and Methods: In this study 80 pregnant women classified into two groups: GroupI:60 consecutive pregnant women who had suffered from two or more miscarriages, and Group II: 20 pregnant women with no history of abortion .The following estimations were done (for each woman in the study): serum homocysteine and vitaminB12 were estimated using ELISA technique. Results: Results showed a significant increase in serum level of homocysteine in the first group compared to control group(p<0.0001) and a low serum level of vitamin B12 which was significantly decreased in the study group (group 1) compared to control group(p<0.0001). Moreover, Our results showed a negative correlation between homocysteine and vitamin B12. Conclusion: The elevated serum homocysteine levels during pregnancy were significantly associated with recurrent pregnancy losses. Moreover, reduced serum vitamin B12 level was considered a risk for recurrent miscarriage. Homocysteine is most sensitive and specificparameters in the recurrent pregnancy losses.

Plasminogen Activator Inhibitor-1 Polymorphism Confers a Genetic Contribution to the Risk of Recurrent Spontaneous Abortion: An Updated Meta-Analysis.

Various studies have investigated the risk of recurrent spontaneous abortion (RSA) with plasminogen activator inhibitor-1 ( PAI-1) 4G/5G polymorphism. However, the results have been somewhat contradictory. Therefore, an updated meta-analysis based on 31 studies (5617 cases and 3952 controls) was undertaken to clarify this relationship. The degree of RSA risk was estimated using the odds ratio (OR) and the 95% confidence interval (CI). Overall, the random effects OR was 1.464 (95% CI: 1.269-1.690) for 4G versus 5G, 2.075 (95% CI: 1.563-2.754) for 4G/4G versus 5G/5G, 1.457 (95% CI: 1.211-1.753) for 4G/5G versus 5G/5G, 1.743 (95% CI: 1.358-2.236) for 4G/4G versus 4G/5G + 5G/5G, and 1.600 (95% CI: 1.327-1.930) for 4G/4G + 4G/5G versus 5G/5G, indicating that PAI-1 4G/5G polymorphism could confer an increased risk of RSA. Furthermore, a subgroup analysis showed a significantly elevated susceptibility to RSA in Asians, Caucasians, and Africans. Thus, this study demonstrated that PAI-1 4G/5G polymorphism likely confers a genetic contribution to the development of RSA. The results may aid in developing a theoretical basis for effective strategies to prevent and treat RSA.

Association between TNF, IL1B, IL6, IL10 and IFNG polymorphisms and recurrent miscarriage: a case control study

BackgroundApproximately half of recurrent miscarriages have unexplained etiology. Recent evidences suggest that cytokines are important determinants in pregnancy maintenance and as such, cytokine gene polymorphisms, which can affect cytokine production and/or functionality, could play a role in the disorder. Thus, we aimed to investigate the association of selected cytokine gene polymorphisms with risk of recurrent miscarriage among Chinese.MethodsTNF -238G > A, TNF -308G > A, IL1B -511 T > C, IL1B 3954C > T, IL6 -174G > C, IL6 -634C > G, IL10 -1082A > G and IFNG 874A > T polymorphisms were genotyped on 775 women with idiopathic recurrent miscarriage and 805 healthy parous control women. Logistic regression analysis was performed to determine the odds ratios (ORs) of the association between the polymorphisms and recurrent miscarriage risk.ResultsAmong the eight polymorphisms studied, only the IL1B -511 T > C and IL6 -634C > G polymorphisms showed statistically significant associations with recurrent miscarriage risk. For the former, a significantly increased risk of recurrent miscarriage was observed for the mutant (CC) genotype (OR: 1.377; 95% CI: 1.039–1.824; P = 0.026). However, for the IL6 -634C > G polymorphism, a decreased recurrent miscarriage risk was observed for the heterozygous (CG) genotype (OR: 0.614; 95% CI: 0.493–0.765; P < 0.001) and the mutant (GG) genotype (OR: 0.414; 95% CI: 0.251–0.684; P = 0.001).ConclusionsThe IL1B -511 T > C polymorphism may serve as important risk factor for recurrent miscarriage while the IL6 -634C > G polymorphism may protect against the risk of recurrent miscarriage.

Evaluation of HLA-G 14-bp ins/del and +3142G>C polymorphisms with susceptibility to recurrent spontaneous abortion

ObjectiveHLA-G is critically important for successful implantation during pregnancy. Increasing evidence supposed that HLA-G plays a key role in tolerance of the semi-allogeneic graft in pregnancy by inhibiting the cytotoxic functions of T and NK cells. The present study aimed to evaluate the impact of HLA-G rs1063320 (+3142G>C) and 14-bp insertion (ins)/deletion (del) polymorphisms on recurrent spontaneous abortion (RSA). Materials and MethodsGenomic DNA from 93 RSA patients and 93 normal fertile women was isolated using the salting out method. Genotyping of HLA-G +3142G>C and 14-bp ins/del variants was done by polymerase chain reaction restriction fragment length polymorphism (PCR-RFP) and PCR method, respectively. ResultsThe HLA-G +3142G>C polymorphism increased the risk of RSA in codominant (OR = 2.39, 95%CI = 1.27–4.49, p = 0.010, GC vs GG; OR = 3.28, 95%CI = 1.16–9.72, p = 0.040, CC vs GG) and dominant (OR = 2.52, 95%CI = 1.37–4.64, p = 0.004, GC + CC vs GG) tested inheritance models. HLA-G rs1063320 C allele was associated with increased risk of RSA (OR = 1.84, 95%CI = 1.20–2.83, p = 0.007). The del/del genotype as well as del allele of 14-bp ins/del variant increased that risk of RSA (OR = 3.02, 95%CI = 1.23–7.41, p = 0.025 and OR = 1.65, 95%CI = 1.09–2.50, p = 0.022, respectively). ConclusionIn summary, our results showed that HLA-G gene polymorphisms significantly increased the risk of RSA in a sample of the Iranian population.

Thrombin-Activatable Fibrinolysis Inhibitor Gene Polymorphism (TAFI1040C/T) in Women With Recurrent Spontaneous Abortion.

Recurrent spontaneous abortion (RSA) is defined as 3 or more consecutive pregnancy failures. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a plasma zymogen that regulates both fibrinolysis and inflammation. The TAFI 1040C/T polymorphism could alter the circulating levels of TAFI with a reduced capacity to remove the fibrin clots from the circulation; therefore, it could be considered a molecular risk factor for RSA. The TAFI 1040C/T polymorphism was studied in 50 patients with RSA by polymerase chain reaction-restriction fragment length polymorphism technique and compared to 50 age- and gender-matched healthy volunteers as a control group to verify its possible association with RSA. In case group, the wild genotype (C/C) and heterozygous genotype (C/T) did not reduce the risk of RSA (odds ratio: 0.368 and 0.767, respectively), even when compared to the number of RSA ( P = .71). A higher frequency of C allele in the control group and a higher frequency of T allele in the case group were observed but with no statistical significance. In conclusion, our study revealed that TAFI 1040C/T could not be considered a molecular predictive factor for RSA in Egyptians.

Rs4265085 in GPER1 gene increases the risk for unexplained recurrent spontaneous abortion in Dai and Bai ethnic groups in China

Oestrogen receptors are implicated in the pathogenesis of recurrent spontaneous abortion (RSA). Non-genomic oestrogen responses can be mediated by GPER. The prevalence of polymorphisms in GPER1 gene in RSA was assessed in 747 Chinese women from Yunnan province (171 Bai, 258 Chinese Han, 234 Dai, 33 Achang and 51 Jingpo patients). Snapshot technology was used for genotyping the polymorphisms of the GPER1 gene. The rs4265085G was significantly increased in the Dai and Bai groups versus controls (Dai: P < 0.0001, Padj < 0.0001, OR 95% CI 2.34 [1.79 to 3.05]; Bai: P = 0.0004, Padj = 0.0012, OR 95% CI 1.71 [1.27 to 2.31]); recessive model of rs4265085 in the Dai (P = 0.003, Padj = 0.009, OR 95% CI 2.71 [1.38 to 5.30]); Bai (P < 0.0001, Padj < 0.0001, OR 95% CI 3.37 [1.93 to 5.91]). Haplotype frequencies containing rs10269151G-rs4265085G-rs11544331C were separately significantly different in Dai and Bai ethnic groups (Dai: P = 0.0002, Padj = 0.001, OR 95% CI = 2.12 [1.43 to 3.17]; Bai: P = 0.005, Padj = 0.025, OR 95% CI = 1.82 [1.18 to 2.78]) compared with controls. The intron variant rs4265085 may confer risk for RSA in Dai and Bai ethnic groups.