Hromadnikova Ilona, Kotlabova Katerina, Hympanova Lucie, Doucha Jindrich, Krofta Ladislav
Department of Molecular Biology and Cell Pathology, Third Faculty of Medicine, Charles University, Ruska 87, 100 00 Prague, Czech Republic.
Department of Molecular Biology and Cell Pathology, Third Faculty of Medicine, Charles University, Ruska 87, 100 00 Prague, Czech Republic; Institute for the Care of the Mother and Child, Third Faculty of Medicine, Charles University, Podolske nabrezi 157/36, 147 00 Prague, Czech Republic.
PLoS One. 2014 Dec 15;9(12):e113735. doi: 10.1371/journal.pone.0113735. eCollection 2014.
The objective of the study was to evaluate risk assessment for gestational hypertension based on the profile of circulating placental specific C19MC microRNAs in early pregnancy.
The prospective longitudinal cohort study of women enrolled at first trimester screening at 10 to 13 weeks was carried out (n = 267). Relative quantification of placental specific C19MC microRNAs (miR-516-5p, miR-517*, miR-518b, miR-520a*, miR-520h, miR-525 and miR-526a) was determined in 28 normal pregnancies and 18 pregnancies which developed gestational hypertension using real-time PCR and a comparative Ct method relative to synthetic C. elegans microRNA (cel-miR-39).
Increased extracellular C19MC microRNA plasmatic levels (miR-516-5p, p<0.001; miR-517*, p = 0.007; miR-520h, p<0.001; miR-518b, p = 0.002) were detected in patients destined to develop gestational hypertension. MiR-520h had the best predictive performance with a PPV of 84.6% at a 7.1% false positive rate. The combination of miR-520h and miR-518b was able to predict 82.6% of women at the same false positive rate. The overall predictive capacity of single miR-518b (73.3% at 14.3% FPR), miR-516-5p (70.6% at 17.9% FPR) and miR-517* (57.9% at 28.6% FPR) biomarkers was lower.
The study brought interesting finding that the up-regulation of miR-516-5p, miR-517*, miR-520h and miR-518b is associated with a risk of later development of gestational hypertension. First trimester screening of extracellular miR-520h alone or in combination with miR-518b identified a significant proportion of women with subsequent gestational hypertension.
本研究的目的是基于孕早期循环胎盘特异性C19MC微小RNA的特征评估妊娠期高血压的风险评估。
对在孕10至13周进行孕早期筛查时入组的女性进行前瞻性纵向队列研究（n = 267）。使用实时PCR和相对于合成秀丽隐杆线虫微小RNA（cel-miR-39）的比较Ct方法，在28例正常妊娠和18例发生妊娠期高血压的妊娠中测定胎盘特异性C19MC微小RNA（miR-516-5p、miR-517*、miR-518b、miR-520a*、miR-520h、miR-525和miR-526a）的相对定量。
在注定要发生妊娠期高血压的患者中检测到细胞外C19MC微小RNA血浆水平升高（miR-516-5p，p<0.001；miR-517*，p = 0.007；miR-520h，p<0.001；miR-518b，p = 0.002）。miR-520h具有最佳预测性能，在假阳性率为7.1%时阳性预测值为84.6%。miR-520h和miR-518b的组合能够在相同假阳性率下预测82.6%的女性。单个miR-518b（在14.3%的假阳性率下为73.3%）、miR-516-5p（在17.9%的假阳性率下为70.6%）和miR-517*（在28.6%的假阳性率下为57.9%）生物标志物的总体预测能力较低。
该研究得出了有趣的发现，即miR-516-5p、miR-517*、miR-520h和miR-518b的上调与后期发生妊娠期高血压的风险相关。孕早期单独筛查细胞外miR-520h或与miR-518b联合筛查可识别出相当比例的后续发生妊娠期高血压的女性。
