Kwon Min-Jung, Kim Ji-Hyang, Lee Jeong-Yong, Ko Eun-Ju, Park Hyeon-Woo, Shin Ji-Eun, Ahn Eun-Hee, Kim Nam-Keun
Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, Korea.
Department of Obstetrics and Gynecology, CHA Bundang Medical Center, School of Medicine, CHA University, Seongnam 13496, Korea.
Biomedicines. 2022 Jun 22;10(7):1481. doi: 10.3390/biomedicines10071481.
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.
复发性流产（RPL）通常定义为妊娠20周前连续发生两次或更多次流产。尽管特发性RPL的病因尚未完全明确，但据报道血管发育和葡萄糖浓度与流产有关。在妊娠中起重要作用的转化生长因子-β（TGF-β）信号通路通过高葡萄糖与SMAD信号之间的相互作用而被激活，并影响血管细胞。SMAD5和RUNX-1参与TGF-β信号通路，并促进晚期糖基化终产物（AGEs）的产生和血管发育。FN3KRP是一个新描述的基因，也与血管疾病有关，并提示与AGEs有关。因此，在本研究中，我们调查了388名患有RPL的韩国女性和280名健康对照女性中，SMAD5、FN3KRP和RUNX-1基因多态性与RPL风险之间的关联。使用实时聚合酶链反应和限制性片段长度多态性分析对参与者进行基因分型，以确定SMAD5 rs10515478 C>G、FN3KRP rs1046875 G>A和RUNX-1 rs15285 G>A多态性的频率。我们发现，患有RPL的女性中FN3KRP rs1046875 AA基因型（校正比值比（AOR），0.553；p = 0.010）和隐性模型（AOR，0.631；p = 0.017）的可能性较低。此外，联合分析表明，SMAD5 rs10515478 C>G和FN3KRP rs1046875 G>A突变等位基因共同与降低的RPL风险相关。这些发现表明，FN3KRP rs1046875 G>A多态性在韩国女性RPL的患病率中起重要作用。鉴于这是第一项表明FN3KRP与妊娠疾病RPL之间存在显著关联的研究，我们的结果表明需要进一步研究FN3KRP在流产中的作用。
