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血管内皮生长因子变体(936C/T、634C/G、2578A/C)及其基因型-单倍型与不孕女性反复种植失败的关联:一项单中心分析研究

Vascular Endothelial Growth Factor Variants (936C/T, 634C/G, 2578A/C) and Their Genotype-Haplotype Association with Recurrent Implantation Failure in Infertile Women: A Single-Center Analytical Study.

作者信息

Procopciuc Lucia Maria, Iancu Mihaela, Caracostea Gabriela Valentina, Goidescu Iulian, Staicu Adelina, Lucaciu Roxana Liana, Hangan Adriana Corina, Gog Bogdan Sidonia, Surcel Mihai

机构信息

Department of Medical Biochemistry, "Iuliu-Hațieganu" University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania.

Medical Informatics and Biostatistics, Department 1, Faculty of Nursing and Health Sciences, "Iuliu-Hațieganu" University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania.

出版信息

Diagnostics (Basel). 2025 Mar 28;15(7):868. doi: 10.3390/diagnostics15070868.

DOI:10.3390/diagnostics15070868
PMID:40218218
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11988517/
Abstract

Vascular Endothelial Growth Factor (VEGF) is a key regulator in angiogenesis and contributes to a successful implantation. The current study has the following objective: to perform genotyping and haplotyping analysis to confirm whether the VEGF-, VEGF-, and VEGF- gene polymorphisms are associated with the susceptibility for recurrent implantation failure (RIF) in Romanian females at reproductive age. In total, 41 infertile women experiencing recurrent implantation failure and 44 women with minor infertility were genotyped for VEGF polymorphisms using PCR-RFLP analysis. The VEGF- polymorphism in the dominant model, (C/T+T/T), represents an increased risk factor for recurrent implantation failure, the odds being 2.70 (95% CI: [1.04, 7.00]). Also, VEGF- gene polymorphism represents the risk factor of RIF under the codominant (adjusted-OR = 5.28, 95% CI: [1.42, 19.65]) and recessive models (adjusted-OR = 5.15, 95% CI: [1.55, 17.09]). Patients carrying the VEGF- allele or VEGF- allele had 2.25-fold and 2.36-fold increased odds of implantation failure (95% CI: [1.05, 4.81], = 0.034) and 95% CI: [1.27, 4.39], = 0.006), respectively. The results of the haplotype-based regression analysis reveal that patient carriers of the VEGF- haplotype had 12.39 increased odds of RIF. Also, carriers of the VEGF- haplotype had 9.56-fold ( = 0.0113) increased odds of RIF after adjusting for age. We found a significant association between VEGF- and VEGF- polymorphisms and the odds of RIF in this cohort of Romanian infertile women. Haplotype analysis suggested the role of VEGF- and VEGF- haplotypes as a risk factors for RIF.

摘要

血管内皮生长因子(VEGF)是血管生成的关键调节因子,对成功着床有重要作用。本研究的目的如下:进行基因分型和单倍型分析,以确定VEGF-、VEGF-和VEGF-基因多态性是否与罗马尼亚育龄女性反复着床失败(RIF)的易感性相关。总共对41例经历反复着床失败的不孕女性和44例轻度不孕女性进行了VEGF多态性的基因分型,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析。显性模型(C/T+T/T)中的VEGF-多态性是反复着床失败的一个增加风险因素,比值比为2.70(95%可信区间:[1.04, 7.00])。此外,VEGF-基因多态性在共显性模型(校正比值比=5.28,95%可信区间:[1.42, 19.65])和隐性模型(校正比值比=5.15,95%可信区间:[1.55, 17.09])下是RIF的风险因素。携带VEGF-等位基因或VEGF-等位基因的患者着床失败的比值比分别增加2.25倍和2.36倍(95%可信区间:[1.05, 4.81],P=0.034)和95%可信区间:[1.27, 4.39],P=0.006)。基于单倍型的回归分析结果显示,携带VEGF-单倍型的患者RIF的比值比增加12.39倍。此外,在调整年龄后,携带VEGF-单倍型的患者RIF的比值比增加9.56倍(P=0.0113)。我们发现,在这组罗马尼亚不孕女性中,VEGF-和VEGF-多态性与RIF的比值比之间存在显著关联。单倍型分析表明,VEGF-和VEGF-单倍型作为RIF的风险因素发挥了作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fe7/11988517/abea7ea47e1f/diagnostics-15-00868-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fe7/11988517/6d8cbbee33f7/diagnostics-15-00868-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fe7/11988517/b1bc190ba192/diagnostics-15-00868-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fe7/11988517/abea7ea47e1f/diagnostics-15-00868-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fe7/11988517/6d8cbbee33f7/diagnostics-15-00868-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fe7/11988517/b1bc190ba192/diagnostics-15-00868-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fe7/11988517/abea7ea47e1f/diagnostics-15-00868-g003.jpg

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本文引用的文献

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ESHRE good practice recommendations on recurrent implantation failure.欧洲人类生殖与胚胎学会关于反复种植失败的良好实践建议。
Hum Reprod Open. 2023 Jun 15;2023(3):hoad023. doi: 10.1093/hropen/hoad023. eCollection 2023.
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Endometrial Angiogenesis of Abnormal Uterine Bleeding and Infertility in Patients with Uterine Fibroids-A Systematic Review.子宫肌瘤患者异常子宫出血和不孕的子宫内膜血管生成:系统评价。
Int J Mol Sci. 2023 Apr 10;24(8):7011. doi: 10.3390/ijms24087011.
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The role of VEGF in cancer-induced angiogenesis and research progress of drugs targeting VEGF.
VEGF 在肿瘤诱导血管生成中的作用及 VEGF 靶向药物的研究进展。
Eur J Pharmacol. 2023 Jun 15;949:175586. doi: 10.1016/j.ejphar.2023.175586. Epub 2023 Mar 9.
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Polymorphic Variants of Genes Encoding Angiogenesis-Related Factors in Infertile Women with Recurrent Implantation Failure.基因编码与血管生成相关因子的多态性变异与复发性种植失败的不孕妇女。
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