Genetic variation in vascular endothelial growth factor gene and its association with recurrent spontaneous abortion

Saboori, Somayeh; Noormohammadi, Zahra; Zare-Karizi, Shohreh

doi:10.4149/bll_2016_016

Cited by 3 publications

(5 citation statements)

References 23 publications

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“…Vascular endothelial growth factor (VEGF) gene family consists of several members including VEGFA, VEGFB, VEGFC, VEGFD and placental growth factor . In turn, VEGFA is identified as the most important angiogenic glycoprotein playing a critical role in angiogenesis of placenta and fetus and is produced by different feto/maternal cell types like endometrium and trophoblastcells . Furthermore, VEGF are believed to regulate endothelial cell proliferation, implantation of embryo, placenta formation and fetal development …”

Section: Introductionmentioning

confidence: 99%

“…5 In turn, VEGFA is identified as the most important angiogenic glycoprotein playing a critical role in angiogenesis of placenta and fetus and is produced by different feto/maternal cell types like endometrium and trophoblastcells. 6,7 Furthermore, VEGF are believed to regulate endothelial cell proliferation, implantation of embryo, placenta formation and fetal development. 6,8 In turn, connexin 43 (Cx43) is considered as another protein that regulates cell proliferation and differentiation 9 and its role in embryonic implantation and placenta formation is well recognized.…”

Section: Introductionmentioning

confidence: 99%

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Association of vascular endothelial growth factor A polymorphisms and aberrant expression of connexin 43 and VEGFA with idiopathic recurrent spontaneous miscarriage

Sajjadi

Ghandil

Shahbazian

et al. 2020

J of Obstet and Gynaecol

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Aim Idiopathic recurrent spontaneous miscarriage (IRSM) is one of the pregnancy outcomes that affects 1–2% of women trying to conceive. Specific genotype or aberrant expression of vascular endothelial growth factor A (VEGFA) and connexin 43 (Cx43) as two important genes for embryonic development are deemed to increase the risk of IRSM. Methods To investigate any possible association of VEGFA polymorphisms and aberrant expression of Cx43 and VEGFA with IRSM, we carried out a case–control study including embryo chorionic villus tissues of 100 pregnant women with IRSM and 100 embryo chorionic villus tissues of healthy pregnant women without history of miscarriage. Restriction fragment length polymorphism was used for genotyping of rs699947 (−2578C/A) and rs2010963 (−634G/C) polymorphisms in VEGFA. Besides, quantitative real‐time PCR was performed for VEGFA and Cx43 expression analysis. Results The results showed that the frequency of −634G/C and C/C genotypes was significantly higher in aborted fetuses (P = 0.001 and P < 0.001, respectively) compared to the control group's. However, the frequency of −2578C/A genotypes was not significantly different between the cases and controls. Moreover, a significant higher expression of VEGF (P = 0.0005) and Cx43 (P = 0.0011) was observed in chorionic villus tissues of women with IRSM. Conclusion The finding demonstrated that IRSM frequency may depend on GC and CC genotypes of rs2010963 VEGF polymorphism and expression level of VEGF and Cx43 in IRSM patients was increased.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of vascular endothelial growth factor A polymorphisms and aberrant expression of connexin 43 and VEGFA with idiopathic recurrent spontaneous miscarriage

Sajjadi

Ghandil

Shahbazian

et al. 2020

J of Obstet and Gynaecol

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“…The results demonstrated that the VEGF 18-bp ins/del variant significantly increased the risk of RSA under codominant, dominant and allelic inheritance models. Previous studies have evaluated the impact of VEGF polymorphisms on the risk of RSA (16,37). Saboori et al (37) examined the possible association between +936 C/T, -1154 G/A, VEGF intron 5 C/T (rs3025010) and +5092 A/C (rs2146323) polymorphisms of the VEGF gene and the risk of RSA.…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies have evaluated the impact of VEGF polymorphisms on the risk of RSA (16,37). Saboori et al (37) examined the possible association between +936 C/T, -1154 G/A, VEGF intron 5 C/T (rs3025010) and +5092 A/C (rs2146323) polymorphisms of the VEGF gene and the risk of RSA. They identified a significant association between the -1154 G/A and VEGF intron 5 C/T variants and the risk of RSA.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2018

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Abstract. 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.

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“…Several studies [14][15][16][17][18][19][20] have been performed in recent years to investigate the effects of VEGFA variants on different disease risks. However, until now, no studies have addressed the effect of VEGFA variants on POI susceptibility in Chinese Han.…”

Section: Introductionmentioning

confidence: 99%

Association of Variants in Vascular Endothelial Growth Factor A Gene and VEGFA Serum Levels with the Risk of Primary Ovarian Insufficiency: A Case-Control Study

Liu

et al. 2021

Gynecol Obstet Invest

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Objective: The study aimed at investigating the association between the vascular endothelial growth factor A (VEGFA) genetic variants, the VEGFA serum level, and the primary ovarian insufficiency (POI) risk in Chinese Han women. Design: An age-matched case-control study was implemented in the West China Second Hospital of Sichuan University. Participants/Materials, Setting, Methods: Blood samples and clinical information were collected from 240 patients with POI and 261 healthy controls between December 2012 and December 2018 at the West China Second Hospital of Sichuan University. Mutations of VEGFA gene −2578C/A, −1154G/A, 936C/T, and −634C/G were identified by PCR-RFLP. Moreover, VEGFA serum levels in the 2 groups were measured by the enzyme-linked immunosorbent assay (ELISA). Results: The −1154G>A and 936C>T variants of the VEGFA gene were significantly associated with POI (the adjusted odds ratio [OR] = 2.17 and 95% confidence interval [CI] = 1.07–4.43 for the former; the adjusted OR = 2.74 and 95% CI = 1.18–6.34 for the latter), whereas no significant difference was found in the genotype distribution of −2578C>A and −634C>G variants between patients and controls (p > 0.05). Moreover, the combined −1154G>A and 936C>T genotype was associated with a significantly increased risk of POI (the adjusted OR = 21.98, 95% CI = 2.78–173.78 among subjects carrying 3 or more variants), particularly when patients aged ≥35 years (the adjusted OR = 20.58, and 95% CI = 2.58–164.25). The POI group exhibited an obviously lower VEGFA serum level (45.15 ± 1.25 pg/mL) than the control group. Compared with the control, the expression of VEGFA was significantly decreased in the POI group (279.90 ± 5.71 pg/mL; p < 0.05). Moreover, the serum VEGFA levels are lower in the −1154AA genotype than those of AG/GG genotypes. Limitations: The main limitation is that all participants enrolled in this study were Chinese. As genotype and allelotype frequencies tend to differ between ethnic populations, extrapolation of the results to other ethnic groups should be cautiously considered. Conclusions: Our study indicates an association between the VEGFA −1154G/A, 936C/T variants, and susceptibility to POI in Chinese Han women. Reduced levels of VEGFA may be a potential mechanism for the development of POI.

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Genetic variation in vascular endothelial growth factor gene and its association with recurrent spontaneous abortion

Cited by 3 publications

References 23 publications

Association of vascular endothelial growth factor A polymorphisms and aberrant expression of connexin 43 and VEGFA with idiopathic recurrent spontaneous miscarriage

Association of vascular endothelial growth factor A polymorphisms and aberrant expression of connexin 43 and VEGFA with idiopathic recurrent spontaneous miscarriage

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

Association of Variants in Vascular Endothelial Growth Factor A Gene and <b><i>VEGFA</i></b> Serum Levels with the Risk of Primary Ovarian Insufficiency: A Case-Control Study

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