Genetic association studies of angiogenesis- and vasoconstriction-related genes in women with recurrent pregnancy loss: a systematic review and meta-analysis

Su, Mei Tsz; Lin, Sheng Hsiang; Chen, Yi Chi

doi:10.1093/humupd/dmr027

Cited by 139 publications

(117 citation statements)

References 63 publications

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“…This reduction is reportedly associated with various vascular diseases such as myocardial infarction (Shimasaki et al, 1998), placental abruption (Yoshimura et al, 2001), and pre-eclampsia (Yoshimura et al, 2000;Savvidou et al, 2001). A meta-analysis has revealed a close association between rs1799983 and idiopathic RM (Su et al, 2011). Our results demonstrated that RM patients had a significantly lower frequency of the G allele of rs1799983, which is consistent with previous studies in Koreans (Shin et al, 2010), whites (Hefler et al, 2002), and Indians (Parveen et al, 2011).…”

Section: Discussionsupporting

confidence: 91%

“…The rs1799983 SNP is associated with various vascular diseases related to pregnancy (Yoshimura et al, 2001;Hefler et al, 2002;Hillermann et al, 2005;Huber et al, 2005;Suryanarayana et al, 2006). A systematic review has indicated that rs1799983 may be correlated with recurrent spontaneous abortion (Su et al, 2011). The rs2070744 SNP has been observed in patients with vascular disease (Khurana et al, 2003;Rossi et al, 2003;Guang-Da et al, 2005); it inhibits the promoter activity of eNOS.…”

Section: Introductionmentioning

confidence: 99%

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Polymorphisms in the endothelial nitric oxide synthase gene associated with recurrent miscarriage

Luo¹,

Li²,

Shan³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Endothelial nitric oxide synthase (eNOS) is an enzyme that influences placental human chorionic gonadotropin production during gestation. Previous studies have indicated an association between eNOS activity, implantation, and maintenance of pregnancy, but proposed associations between polymorphisms of the eNOS gene and recurrent miscarriage (RM) are controversial. To identify markers contributing to the genetic susceptibility to RM, we examined the potential association between RM and 8 single nucleotide polymorphisms (SNPs; rs1799983, rs2070744, rs11771443, rs3918188, rs2853796, rs7830, rs1541861, and rs2853792) of the eNOS gene using the MassARRAY system (Sequenom, USA). The enrolled participants included 192 RM patients and 201 women with normal fertility as controls. The results showed that rs1799983 at exon 7 of the eNOS gene was significantly associated with RM (genotype: chi-square = 15.071, P = 0.001; allele: chi-square = 6.250, P = 0.016). Another significant association was observed for rs11771443 in the promoter (genotype: chi-square = 6.259, P = 0.044; allele: chi-square = 7.076, P = 0.008). Furthermore, strong linkage disequilibrium was observed in 3 blocks (Dꞌ > 0.9), and significantly fewer T-T-G haplotypes (chi-square = 5.981, P = 0.015) residing in block 1 were found in RM patients. These findings point to a role for eNOS gene polymorphisms in RM in the Chinese Han population and may be informative for future genetic or neurobiological studies of RM.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Polymorphisms in the endothelial nitric oxide synthase gene associated with recurrent miscarriage

Luo¹,

Li²,

Shan³

et al. 2013

Genet. Mol. Res.

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“…Expression of VEGF-A and VEGF-C has been demonstrated in the human endometrium throughout the menstrual cycle with an increase in the late proliferative and secretory phases (13,14). In addition, VEGF's expression was found in decidual cells of early pregnancy (15). On the other hand, expression of VEGF receptors was shown in human endometrium (13).…”

Section: Introductionmentioning

confidence: 99%

Association of angiogenic cytokines (VEGF-A and VEGF-C) and clinical characteristic in women with unexplained recurrent miscarriage

Bagheri¹,

Kumar²,

Kamath³

et al. 2017

BLL

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INTRODUCTION: Recurrent miscarriage (RM) defi ned as 2 or more spontaneous miscarriage before 20 weeks of gestation, affects at least 1 % of couples trying to conceive. In over 50 % of cases, the cause of the loss of pregnancy remains unexplained. Reduced expression of Angiogenic factors such as: vascular endothelial growth factor (VEGF-A) and VEGF-C has been linked with spontaneous miscarriage, likely due to defective foetal and placental angiogenesis. AIMS AND OBJECTIVES: To investigate the relationships between serum level of VEGF-A and VEGF-C with clinical characteristic in women with URM and compare to pregnant and healthy women. MATERIALS AND METHODS: A case-control study, which was conducted between 90 non-pregnant women with history of RM, age-matched with 70 non-pregnant women without history of recurrent abortion with at least one child (controls) and 70 pregnant women without history of recurrent abortion with at least one child (controls). Those with unexplained RM were eligible. Demographic and Anthropometric data were retrieved by pre-test questionnaire and serum level of VEGF-A and VEGF-C measured by ELISA kit. RESULTS: This study showeds that maternal levels of VEGF-A and VEGF-C were distinctly lower in RSA (189.87±88.1 vs 238.8±99.6) compared to healthy (239.1±99.7 vs 275.5±133.08) and pregnant (301.5±76.4 vs 402.5±128.6) women as control groups. Univariate analysis demonstrated that clinical characteristic factors were signifi cantly associated with concentration of VEGF-A and VEGF-C in cases and controls. CONCLUSIONS: Our fi ndings suggest that these molecules could be used as potential predictive markers of miscarriage in these women presenting with URM (Tab. 4, Fig. 5, Ref. 40). Text in PDF www.elis.sk.

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“…The quality of the included studies was assessed according to the following criteria from the previous meta-analysis [28]: …”

Section: Data Extractionmentioning

confidence: 99%

Relationship between HLA-G polymorphism and susceptibility to recurrent miscarriage: A meta-analysis of non-family-based studies

Fan

Huang

et al. 2013

J Assist Reprod Genet

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Purpose The HLA-G 14-bp insertion/deletion polymorphism had been inconsistently associated with recurrent miscarriage (RM) risk. We examined the association by performing a meta-analysis. Methods Eligible articles were searched in PubMed, EMBASE and CNKI without language limitation. We included all the articles about two or more miscarriages associated with HLA-G 14-bp polymorphism. The odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of associations. Statistical analyses were performed by the STATA10.0 software. Results 17 studies were included, representing 1786 cases and 1574 controls. The current meta-analysis showed that 14-bp polymorphism was not associated with RM risk in all genetic models and allele contrast(+14 bp vs. −14 bp: OR=1.13; 95 % CI, 0.96,1.32; +14 bp/+14 bp vs. −14 bp/−14 bp: OR=1.16, 95 % CI, 0.85, 1.59; +14 bp/−14 bp vs. −14 bp/−14 bp: OR= 1.21, 95 % CI, 0.92,1.58; dominant model: OR=1.33; 95 % CI, 0.99,1.78; recessive model: OR = 1.06; 95 % CI, 0.79,1.43). Moreover, a significant heterogeneity was evident across studies. On the other hand, the subgroup analysis demonstrated that there was a significant association between HLA-G 14-bp polymorphism and patients with three or more miscarriages(+14 bp vs. −14 bp: OR=1.27; 95 % CI, 1.04, 1.55; dominant model: OR=1.52; 95 % CI, 1.16, 1.99; and model +14 bp/−14 bp versus −14 bp/−14 bp: OR=1.51; 95 % CI, 1.15, 1.97;). Conclusions Our comprehensive meta-analysis indicated that there was insufficient evidence to demonstrate a conclusive association between the HLA-G 14-bp insertion/deletion polymorphism and the risk of RM. But HLA-G 14-bp insertion/ deletion polymorphic variation was associated with RM risk in patients with three or more miscarriages. Larger and welldesigned studies may eventually provide a better, comprehensive understanding of the association between the HLA-G 14-bp insertion/deletion polymorphism and RM in the future.

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Genetic association studies of angiogenesis- and vasoconstriction-related genes in women with recurrent pregnancy loss: a systematic review and meta-analysis

Abstract: Meta-analyses of available data showed significant associations between the VEGF (-1154G>A), p53 (codon72) and eNOS (Glu298Asp) polymorphisms and idiopathic RPL. These angiogenesis- and vasoconstriction-related genes jointly confer higher susceptibility to idiopathic RPL.

Cited by 139 publications

References 63 publications

Polymorphisms in the endothelial nitric oxide synthase gene associated with recurrent miscarriage

Polymorphisms in the endothelial nitric oxide synthase gene associated with recurrent miscarriage

Association of angiogenic cytokines (VEGF-A and VEGF-C) and clinical characteristic in women with unexplained recurrent miscarriage

Relationship between HLA-G polymorphism and susceptibility to recurrent miscarriage: A meta-analysis of non-family-based studies

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