Implications of VEGF gene sequence variations and its expression in recurrent pregnancy loss

Amin, Ina; Pandith, Arshad A.; Manzoor, Usma; Mir, Syed; Afroze, Dil; Koul, Aabid; Wani, Saima; Ahmad, Aabida; Qasim, Iqbal; Rashid, Masarat; Wani, Umer Majeed; Anwar, Iqra; Aein, Qurat ul; Mansoor, Sheikh

doi:10.1016/j.rbmo.2021.08.009

Cited by 7 publications

(4 citation statements)

References 42 publications

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“…In the case of SNP VEGF rs1570360 (−1154G > A), the variant allele A was significantly more common in patients with RPL (0.41) than in controls (0.19) ( p < 0.0001). In VEGF -583 C > T, the CT genotype was significantly associated with this pathological state ( p = 0.003) [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

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DNA Polymorphisms in Pregnant Women with Sticky Platelet Syndrome

Stančiaková

Žolková

Vadelová

et al. 2022

JCM

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Sticky platelet syndrome (SPS) is a thrombophilia caused by the increased aggregability of platelets in response to the addition of low concentrations of epinephrine (EPI) and/or adenosine diphosphate (ADP). Some of the single nucleotide polymorphisms (SNP), alleles and haplotypes of platelet glycoprotein receptors were proved to have a role in the etiology of thrombotic episodes When comparing SPS and the control group, in VEGFA rs3025039, the p value for both CC vs. TT and CT vs. TT analyses was <0.001. Interestingly, no minor TT genotype was present in the SPS group, suggesting the thrombotic pathogenesis of recurrent spontaneous abortions (RSA) in these patients. Moreover, we found a significant difference in the presence of AT containing a risky A allele and TT genotype of ALPP rs13026692 (p = 0.034) in SPS patients when compared with the controls. Additionally, we detected a decreased frequency of the GG (CC) genotype of FOXP3 rs3761548 in patients with SPS and RSA when compared with the control group (p value for the CC (GG) vs. AA (TT) 0.021). This might indicate an evolutionary protective mechanism of the A (T) allele in the SPS group against thrombotic complications in pregnancy. These results can be used for antithrombotic management in such pregnant patients.

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Section: Discussionmentioning

confidence: 99%

“…In VEGF 634 G > C, the allele C and CC genotype are significantly more frequent in individuals with RPL than in the control group ( p < 0.0001) [ 43 ]. Thus, the frequency of idiopathic RSA can be dependent on the GC and CC genotype of rs2010963 VEGF polymorphism [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

DNA Polymorphisms in Pregnant Women with Sticky Platelet Syndrome

Stančiaková

Žolková

Vadelová

et al. 2022

JCM

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“…Amin et al. found that the heterozygous genotype GA was significantly associated with the overexpression and underexpression of VEGF mRNA, while the homozygous variant genotype AA only decreased the VEGF mRNA levels in RPL patients by genotyping and quantitative real-time PCR (qRT–PCR-PCR) ( 37 ). Another similar study indicated that the 3’-untranslated region of VEGF resulted in susceptibility to RPL in Korean women ( 38 ).…”

Section: Omics Studies Investigating the Establishment And Maintenanc...mentioning

confidence: 99%

Multiomics Studies Investigating Recurrent Pregnancy Loss: An Effective Tool for Mechanism Exploration

Wang

Ding

et al. 2022

Front. Immunol.

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Patients with recurrent pregnancy loss (RPL) account for approximately 1%-5% of women aiming to achieve childbirth. Although studies have shown that RPL is associated with failure of endometrial decidualization, placental dysfunction, and immune microenvironment disorder at the maternal-fetal interface, the exact pathogenesis remains unknown. With the development of high-throughput technology, more studies have focused on the genomics, transcriptomics, proteomics and metabolomics of RPL, and new gene mutations and new biomarkers of RPL have been discovered, providing an opportunity to explore the pathogenesis of RPL from different biological processes. Bioinformatics analyses of these differentially expressed genes, proteins and metabolites also reflect the biological pathways involved in RPL, laying a foundation for further research. In this review, we summarize the findings of omics studies investigating decidual tissue, villous tissue and blood from patients with RPL and identify some possible limitations of current studies.

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“…Recent studies showed that either vascular function or glucose-related genes influence RPL risk [ 38 , 39 , 40 ]. In addition, we previously found that pregnancy disorders are associated with genetic polymorphisms in 3′-untranslated regions (3′-UTRs) [ 41 , 42 ].…”

Section: Introductionmentioning

confidence: 99%

Genetic Polymorphisms in the 3′-Untranslated Regions of SMAD5, FN3KRP, and RUNX-1 Are Associated with Recurrent Pregnancy Loss

et al. 2022

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Recurrent pregnancy loss (RPL) is typically defined as two or more consecutive pregnancy losses prior to 20 weeks of gestation. Although the causes of idiopathic RPL are not completely understood, vascular development and glucose concentration were reported to correlate with the pregnancy loss. The TGF-β signaling pathway which plays a significant role in pregnancy is activated by the interaction between high glucose and SMAD signaling and affects the vascular cells. SMAD5 and RUNX-1 are involved in the TGF-β signaling pathway and contribute to advanced glycation end products (AGEs) production and vascular development. FN3KRP, a newly described gene, is also associated with vascular diseases and suggested to relate to AGEs. Therefore, in the present study, we investigated associations between RPL risk and genetic polymorphisms of SMAD5, FN3KRP, and RUNX-1 in 388 women with RPL and 280 healthy control women of Korean ethnicity. Participants were genotyped using real-time polymerase chain reaction and restriction fragment length polymorphism assay to determine the frequency of SMAD5 rs10515478 C>G, FN3KRP rs1046875 G>A, and RUNX-1 rs15285 G>A polymorphisms. We found that women with RPL had lower likelihoods of the FN3KRP rs1046875 AA genotype (adjusted odds ratio (AOR), 0.553; p = 0.010) and recessive model (AOR, 0.631; p = 0.017). Furthermore, combination analysis showed that SMAD5 rs10515478 C>G and FN3KRP rs1046875 G>A mutant alleles were together associated with reduced RPL risk. These findings suggest that the FN3KRP rs1046875 G>A polymorphism has a significant role on the prevalence of RPL in Korean women. Considering that it is the first study indicating a significant association between FN3KRP and pregnancy disease, RPL, our results suggest the need for further investigation of the role of FN3KRP in pregnancy loss.

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Implications of VEGF gene sequence variations and its expression in recurrent pregnancy loss

Cited by 7 publications

References 42 publications

DNA Polymorphisms in Pregnant Women with Sticky Platelet Syndrome

DNA Polymorphisms in Pregnant Women with Sticky Platelet Syndrome

Multiomics Studies Investigating Recurrent Pregnancy Loss: An Effective Tool for Mechanism Exploration

Genetic Polymorphisms in the 3′-Untranslated Regions of SMAD5, FN3KRP, and RUNX-1 Are Associated with Recurrent Pregnancy Loss

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