Association of Single Nucleotide Polymorphisms in Vascular Endothelial Growth Factor with Recurrent Pregnancy Loss in Erbil Province: A Molecular Investigation
DOI:
https://doi.org/10.21271/ZJPAS.38.1.4Keywords:
Recurrent pregnancy loss, vascular endothelial growth factor, Single-nucleotide polymorphism, AngiogenesisAbstract
Recurrent pregnancy loss (RPL) is defined as two or more failed pregnancies before 20 weeks of gestation. Genetic polymorphisms, especially alterations in the vascular endothelial growth factor (VEGF) gene, may increase the risk of pregnancy loss. This study aimed to investigate the connection between changes in the VEGF-A gene (-460C/T, -1190A/G, and -1154A/G) and RPL in women from the Erbil Province. The study included 60 women with a history of RPL and 30 healthy women with no history of miscarriage. Genomic DNA was isolated from whole blood samples. The VEGF-A promoter region was amplified using Touchdown PCR, and the resulting PCR products were analyzed by agarose gel electrophoresis and then processed for Sanger sequencing. Statistical analysis was performed using Yates-corrected χ² tests or Fisher's exact tests for small sample sizes. The results demonstrated that the -460 TT genotype was markedly more prevalent in RPL patients than in controls, increasing the risk by 3.3 times. The -460T allele significantly increased the probability of RPL (OR = 3.3, p = 0.0025, 95% CI: 1.49–7.29). For the -1190A/G polymorphism, the homozygous GG genotype was more prevalent in RPL cases, and the -1190G allele was associated with an increased risk (OR = 2.64, p = 0.0138, 95% CI: 1.26–5.52), identifying it as the risk allele for this SNP. In contrast, the -1154A/G polymorphism showed no significant differences in either genotype or allele frequencies between RPL cases and controls (p > 0.05). These findings suggest that some genotypic alterations, notably -460 TT and -1190 GG, may act as genetic risk factors for RPL.
References
ABU-GHAZALEH, N., BRENNECKE, S., MURTHI, P. & KARANAM, V. 2023. Association of vascular endothelial growth factors (VEGFs) with recurrent miscarriage: a systematic review of the literature. International Journal of Molecular Sciences, 24, 9449.
AGGARWAL, S., PARVEEN, F., FARIDI, R. M., PHADKE, S., BORKAR, M. & AGRAWAL, S. 2011. Vascular endothelial growth factor gene polymorphisms in North Indian patients with recurrent miscarriages. Reproductive BioMedicine Online, 22, 59-64.
AJAZ, S., MUNEER, R., SIDDIQA, A., ALI MEMON, M., FIRASAT, S., ABID, A. & KHALIQ, S. 2021. Association of specific single nucleotide variants (SNVs) in the promoter and 3′-Untranslated region of Vascular Endothelial growth factor (VEGF) gene with risk and higher tumour grade of head and neck cancers. Oral Oncology, 122, 105519.
ALMAWI, W. Y., GAMMOH, E., MALALLA, Z. H. & AL-MADHI, S. A. 2016. Analysis of VEGFA Variants and Changes in VEGF Levels Underscores the Contribution of VEGF to Polycystic Ovary Syndrome. PLoS One, 11, e0165636.
ALMAWI, W. Y., SALDANHA, F. L., MAHMOOD, N. A., AL-ZAMAN, I., SATER, M. S. & MUSTAFA, F. E. 2013. Relationship between VEGFA polymorphisms and serum VEGF protein levels and recurrent spontaneous miscarriage. Human Reproduction, 28, 2628-2635.
BUROKER, N. E. 2014. VEGFA rSNPs, transcriptional factor binding sites and human disease. The Journal of Physiological Sciences, 64, 73-76.
COSTESCU, D., GUILBERT, E., BERNARDIN, J., BLACK, A., DUNN, S., FITZSIMMONS, B., NORMAN, W. V., PYMAR, H., SOON, J. & TROUTON, K. 2016. Medical abortion. Journal of Obstetrics and Gynaecology Canada, 38, 366-389.
FAILLA, C. M., CARBONE, M. L., RAMONDINO, C., BRUNI, E. & ORECCHIA, A. 2024. Vascular Endothelial Growth Factor (VEGF) Family and the Immune System: Activators or Inhibitors? Biomedicines, 13.
GUO, X., YI, H., LI, T. C., WANG, Y., WANG, H. & CHEN, X. 2021. Role of Vascular Endothelial Growth Factor (VEGF) in Human Embryo Implantation: Clinical Implications. Biomolecules, 11.
HOLMES, D. I. & ZACHARY, I. 2005. The vascular endothelial growth factor (VEGF) family: angiogenic factors in health and disease. Genome Biol, 6, 209.
KANG, Y., LI, H., LIU, Y. & LI, Z. 2024. Regulation of VEGF-A expression and VEGF-A-targeted therapy in malignant tumors. J Cancer Res Clin Oncol, 150, 221.
LI, J., WANG, L., DING, J., CHENG, Y., DIAO, L., LI, L., ZHANG, Y. & YIN, T. 2022. Multiomics Studies Investigating Recurrent Pregnancy Loss: An Effective Tool for Mechanism Exploration. Front Immunol, 13, 826198.
LI, L., DONGHONG, L., SHUGUANG, W., HONGBO, Z., JING, Z. & SHENGBIN, L. 2013. Polymorphisms in the vascular endothelial growth factor gene associated with recurrent spontaneous miscarriage. The Journal of Maternal-Fetal & Neonatal Medicine, 26, 686-690.
MROZIKIEWICZ, A. E., KURZAWIŃSKA, G., OŻAROWSKI, M., WALCZAK, M., OŻEGOWSKA, K. & JĘDRZEJCZAK, P. 2023. Polymorphic Variants of Genes Encoding Angiogenesis-Related Factors in Infertile Women with Recurrent Implantation Failure. Int J Mol Sci, 24.
PAPAZOGLOU, D., GALAZIOS, G., PAPATHEODOROU, K., LIBERIS, V., PAPANAS, N., MALTEZOS, E. & MAROULIS, G. B. 2005. Vascular endothelial growth factor gene polymorphisms and idiopathic recurrent pregnancy loss. Fertil Steril, 83, 959-63.
ŞAMLı, H., DEMIR, B., ÖZGÖZ, A., ATALAY, M. & UNCU, G. 2012. Vascular endothelial growth factor gene 1154 G/A, 2578 C/A, 460 C/T, 936 C/T polymorphisms and association with recurrent pregnancy losses. Genet Mol Res, 11, 4739-4745.
TURESHEVA, A., AIMAGAMBETOVA, G., UKYBASSOVA, T., MARAT, A., KANABEKOVA, P., KALDYGULOVA, L., AMANZHOLKYZY, A., RYZHKOVA, S., NOGAY, A., KHAMIDULLINA, Z., ILMALIYEVA, A., ALMAWI, W. Y. & ATAGELDIYEVA, K. 2023. Recurrent Pregnancy Loss Etiology, Risk Factors, Diagnosis, and Management. Fresh Look into a Full Box. J Clin Med, 12.
XING, X., YAN, J., ZHAO, Y., YOU, L., BIAN, Y. & CHEN, Z. J. 2011. Association of vascular endothelial growth factor gene polymorphisms with recurrent spontaneous abortion in Chinese Han women. Am J Reprod Immunol, 65, 521-5.
YANG, X., DENG, Y., GU, H., LIM, A., ALTANKHUYAG, A., JIA, W., MA, K., XU, J., ZOU, Y., SNELLINGEN, T., LIU, X., WANG, N. & LIU, N. 2011. Polymorphisms in the vascular endothelial growth factor gene and the risk of diabetic retinopathy in Chinese patients with type 2 diabetes. Mol Vis, 17, 3088-96.
ZENG, H., HU, L., XIE, H., MA, W. & QUAN, S. 2021. Polymorphisms of vascular endothelial growth factor and recurrent implantation failure: a systematic review and meta-analysis. Arch Gynecol Obstet, 304, 297-307.
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