Abstract：
Fibroblast growth factor 5 (FGF5), which is a well-established causative factor for blood pressure, has been identified as a susceptibility gene for preeclampsia (PE) in European and Central Asian women. Here, we examined whether polymorphism rs16998073 in FGF5 confer a significant risk to PE in Chinese Han population by case-control association analysis. FGF5 rs16998073 was genotyped by Sanger sequencing in women with preeclampsia (n = 187) and healthy controls (n = 229) of Han Chinese. We found the frequency of rs16998073T allele was significantly higher in PE patients than that in controls. Next, we utilized dual-luciferase reporter assays and electrophoretic mobility shift assay (EMSA) reactions to investigate whether rs16998073 different alleles could affect the transcriptional activity of FGF5. The dual luciferase reporter assay showed that T allele increased the transcriptional efficiency by 1.5-fold compared with the G allele. Similarly, EMSA revealed that the T allele had a strong transcription factor binding strength compared with the G allele. We then examined the mRNA and protein expression levels of FGF5 in placental tissues by real-time PCR and Western blot assays. We found FGF5 were significantly upregulated in placental tissues from PE patients or PE mouse model than their corresponding controls. In addition, in vitro cell experiments confirmed that FGF5 could promote cell apoptosis of HTR8/SVneo and inhibit cell invasion. Taken together, our data provide evidence implicating rs16998073 of FGF5 as a functional genetic risk variant for PE disease and FGF5 might participate in development of PE disease.
摘要：
成纤维细胞生长因子5（FGF5），这是血压的一个公认的致病因素，已被确定为欧洲和中亚妇女先兆子痫（PE）的易感基因。这里,我们通过病例-对照关联分析,研究了FGF5基因rs16998073多态性在中国汉族人群中是否具有PE的显著风险.通过Sanger测序对患有先兆子痫的女性（n=187）和汉族健康对照（n=229）的FGF5rs16998073进行基因分型。我们发现PE患者rs16998073T等位基因的频率明显高于对照组。接下来,我们利用双荧光素酶报告基因测定和电泳迁移率变化测定(EMSA)反应来研究rs16998073不同等位基因是否会影响FGF5的转录活性.双荧光素酶报告基因分析显示,与G等位基因相比,T等位基因的转录效率提高了1.5倍。同样，EMSA显示，与G等位基因相比，T等位基因具有很强的转录因子结合强度。然后，我们通过实时PCR和Western印迹测定法检查了胎盘组织中FGF5的mRNA和蛋白质表达水平。我们发现来自PE患者或PE小鼠模型的胎盘组织中的FGF5比它们相应的对照显著上调。此外,体外细胞实验证实FGF5能促进HTR8/SVneo细胞凋亡,抑制细胞侵袭。一起来看,我们的数据提供了证据,提示FGF5的rs16998073是PE疾病的功能性遗传风险变异,FGF5可能参与PE疾病的发展.
