Reference values for circulating pregnancy-associated microRNAs in maternal plasma and their clinical usefulness in uncomplicated pregnancy and hypertensive disorder of pregnancy

Reference values for circulating pregnancy-associated microRNAs in maternal plasma and their clinical usefulness in uncomplicated pregnancy and hypertensive disorder of pregnancy
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DOI:
10.1111/jog.13610
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发表时间:
2018-05-01
影响因子:
1.6
通讯作者:
Masuzaki, Hideaki
Masuzaki, Hideaki
中科院分区:
医学4区
文献类型:
--
作者:
Murakami, Yuko;Miura, Kiyonori;Masuzaki, Hideaki

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目的:本研究的目的是建立孕妇血浆中循环妊娠相关胎盘microRNA的参考值,并阐明其在妊娠期高血压疾病(HDP)患者中的临床意义。从145名无并发症妊娠的妇女中采集血液样本(分别为妊娠12、23、30和36周的24、26、31和32名女性,以及分娩后1天的32名女性)。通过实时定量逆转录聚合酶链反应测定妊娠相关胎盘microRNA(miR-515- 3 p、miR-517 a、miR-517 c和miR-518 b)的血浆浓度。每个microRNA的参考值通过最佳拟合线和95%预测区间确定,并表示为对数转换。为了阐明这些参考值的临床意义,我们测量了不同人群中妊娠相关microRNA的血浆浓度,这些人群包括33名HDP孕妇和44名无并发症妊娠的妇女。19号染色体上循环妊娠相关胎盘microRNA的参考值随妊娠进展呈上升趋势,分娩后1天显著下降(P < 0.05)。miR-515- 3 p、miR-517 a、miR-517 c和miR-518 b各参考值的敏感性和特异性分别为57.6%和93.2%、63.6%和75.0%、75.8%和79.5%、63.6%和75.0%。miR-515- 3 p、miR-517 a、miR-517 c和miR-518 b的阳性和阴性预测值分别为86.4%和74.5%、65.6%和73.3%、73.5%和81.4%。建立母体血浆中循环妊娠相关胎盘microRNA的参考值可能有助于评估HDP。
Aim: The aim of this study was to establish the reference values for circulating pregnancy-associated placental microRNAs in maternal plasma and clarify their clinical significance in patients with hypertensive disorder of pregnancy (HDP).Methods: Blood samples were collected from 145 women with uncomplicated pregnancies (24, 26, 31 and 32 women at 12, 23, 30 and 36 weeks of gestation, respectively, and 32 women 1 day after delivery). Plasma concentrations of pregnancy-associated placental microRNAs (miR-515-3p, miR-517a, miR-517c and miR-518b) were measured by quantitative real-time reverse-transcription polymerase chain reaction. Reference values for each microRNA were determined by the line of best fit and 95% prediction interval and are expressed as logarithmic transformation. To clarify the clinical significance of these reference values, we measured the plasma concentrations of pregnancy-associated microRNAs in a different population comprising 33 pregnant women with HDP and 44 women with uncomplicated pregnancies.Results: Reference values for circulating pregnancy-associated placental microRNAs on chromosome 19 miRNA clusters showed an increasing tendency as pregnancy progressed and decreased significantly 1 day after delivery (P < 0.05). The sensitivity and specificity of each reference value were 57.6% and 93.2% for miR-515-3p, 63.6% and 75.0% for miR-517a, 75.8% and 79.5% for miR-517c and 63.6% and 75.0% for miR-518b, respectively. The positive and negative predictive values of each reference value were 86.4% and 74.5% for miR-515-3p, 65.6% and 73.3% for miR-517a, 73.5% and 81.4% for miR-517c and 65.6% and 73.3% for miR-518b, respectively.Conclusion: Establishing the reference values for circulating pregnancy-associated placental microRNAs in maternal plasma could be useful for the evaluation of HDP.