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复发性流产中血管内皮生长因子受体-2(KDR)-604A>G多态性的测定

Determination of VEGFR-2 (KDR) -604A>G polymorphism in recurrent pregnancy loss.

作者信息

Boldeanu Lidia, Siloşi Cristian Adrian, Pădureanu Vlad, Dijmărescu Anda Lorena, Manolea Maria Magdalena, Tabacu Maria Carmen, Boldeanu Mihail Virgil, Popescu-Drigă Mircea Vasile, Poenariu Ioan Sabin, Pădureanu Rodica, Novac Liliana Victoria, Novac Marius Bogdan

机构信息

Department of Immunology, University of Medicine and Pharmacy of Craiova, Romania;

出版信息

Rom J Morphol Embryol. 2018;59(4):1053-1059.

Abstract

BACKGROUND

Placental angiogenesis and vascular adaptation during pregnancy, along with diminished placental trophoblastic vascular endothelial growth factor immunoreactivity, play an important role in the early stages of human pregnancy, being possible causes of recurrent pregnancy loss (RPL).

AIMS

Our focus was directed towards investigating a possible association between vascular endothelial growth factor receptor-2 (kinase insert domain receptor) VEGFR-2 (KDR) -604A>G (rs 2071559) gene polymorphism and RPL in the study area of Dolj County, Romania.

PATIENTS, MATERIALS AND METHODS: In this study, 169 women, diagnosed with RPL, were included. They were hospitalized in the Clinics of Obstetrics and Gynecology, "Filantropia" Municipal Hospital, Craiova, during the following period: October 2009-October 2016. The control group consisted of 145 women. All subjects were genotyped by means of allelic discrimination TaqMan polymerase chain reaction assay with specific probes.

RESULTS

No statistically significant difference was observed between the RPL patients and the control group, when one genotype was compared to another [in a dominant model, -604 AG+GG vs. AA: odds ratio (OR) 1.71, 95% confidence interval (CI) 0.99-2.96, p=0.051]. While studying the overall risk of RPL by the genotype frequencies of KDR polymorphism between controls and RPL patients, which were stratified according to the number of consecutive pregnancy losses (PLs), the chi-square test showed a significant association between the presence of this polymorphism and the increased risk observed in patients with four or more consecutive PLs, to develop RPL (in a dominant model - G allele carriers, KDR -604 AG+GG vs. AA: OR 1.91, 95% CI 1.03-3.52, p=0.037). These results prove that G allele carriers have an increased risk of RPL about 1.91-fold higher than those with the AA genotype do. Although our results bear limited statistical significance, the study nonetheless represents a step forward in the evaluation of recurrent abortion, which has not yet been explored sufficiently.

CONCLUSIONS

VEGFR-2 (KDR) polymorphism does not influence RPL susceptibility in the study area of Dolj County, Romania. Therefore, further studies, which include a larger sample size, are required in order to clarify the role of KDR polymorphism in RPL.

摘要

背景

孕期胎盘血管生成和血管适应性变化,以及胎盘滋养层血管内皮生长因子免疫反应性降低,在人类妊娠早期起着重要作用,可能是复发性流产(RPL)的原因。

目的

我们的研究重点是调查罗马尼亚多尔日县研究区域内血管内皮生长因子受体2(激酶插入结构域受体)VEGFR - 2(KDR)-604A>G(rs 2071559)基因多态性与复发性流产之间的可能关联。

患者、材料与方法:本研究纳入了169例被诊断为复发性流产的女性。她们于2009年10月至2016年10月期间在克拉约瓦市“慈善”市立医院妇产科诊所住院。对照组由145名女性组成。所有受试者均通过等位基因鉴别TaqMan聚合酶链反应检测法及特异性探针进行基因分型。

结果

当比较一种基因型与另一种基因型时,复发性流产患者与对照组之间未观察到统计学上的显著差异[在显性模型中,-604 AG + GG与AA相比:比值比(OR)为1.71,95%置信区间(CI)为0.99 - 2.96,p = 0.051]。在根据连续流产次数(PLs)对对照组和复发性流产患者进行分层,研究KDR多态性基因型频率与复发性流产总体风险时,卡方检验显示该多态性的存在与连续4次或更多次流产的患者发生复发性流产的风险增加之间存在显著关联(在显性模型中 - G等位基因携带者,KDR -604 AG + GG与AA相比:OR为1.91,95% CI为1.03 - 3.52,p = 0.037)。这些结果证明,G等位基因携带者发生复发性流产的风险比AA基因型携带者高约1.91倍。尽管我们的结果在统计学上的意义有限,但该研究仍是复发性流产评估方面向前迈出的一步,而复发性流产尚未得到充分研究。

结论

在罗马尼亚多尔日县研究区域内,VEGFR - 2(KDR)多态性不影响复发性流产易感性。因此,需要进一步开展样本量更大的研究,以阐明KDR多态性在复发性流产中的作用。

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