Department of Health Promotion and Development, School of Nursing, University of Pittsburgh, Pittsburgh, PA, USA.
Biol Res Nurs. 2011 Apr;13(2):134-9. doi: 10.1177/1099800410385448. Epub 2010 Nov 1.
The goal of this study was to further validate eight candidate genes identified in a microarray analysis of first trimester placentas in preeclampsia.
Surplus chorionic villus sampling (CVS) specimens of 4 women subsequently diagnosed with preeclampsia (PE) and 8 control women (C) without preeclampsia analyzed previously by microarray and 24 independent additional control samples (AS) were submitted for confirmatory studies by quantitative real-time polymerase chain reaction (qRT-PCR).
Downregulation was significant in FSTL3 in PE as compared to C and AS (p = .04). PAEP was downregulated, but the difference was only significant between C and AS (p = .002) rather than between PE and either of the control groups. Expression levels for CFH, EPAS1, IGFBP1, MMP12, and SEMA3C were not statistically different among groups, but trends were consistent with microarray results; there was no anti-correlation. S100A8 was not measurable in all samples, probably because different probes and primers were needed.
This study corroborates reduced FSTL3 expression in the first trimester of preeclampsia. Nonsignificant trends in the other genes may require follow-up in studies powered for medium or medium/large effect sizes. qRT-PCR verification of the prior microarray of CVS may support the placental origins of preeclampsia hypothesis. Replication is needed for the candidate genes as potential biomarkers of susceptibility, early detection, and/or individualized care of maternal-infant preeclampsia.
本研究的目的是进一步验证在子痫前期的早孕期胎盘的微阵列分析中确定的 8 个候选基因。
对先前通过微阵列分析的 4 名随后被诊断为子痫前期(PE)的女性和 8 名无子痫前期的对照女性(C)的多余绒毛膜绒毛取样(CVS)标本以及 24 个独立的对照样本(AS)进行了定量实时聚合酶链反应(qRT-PCR)的确认研究。
与 C 和 AS 相比,PE 中 FSTL3 的下调具有显著性(p=0.04)。PAEP 下调,但差异仅在 C 和 AS 之间显著(p=0.002),而不是在 PE 和对照组之间。CFH、EPAS1、IGFBP1、MMP12 和 SEMA3C 的表达水平在各组之间无统计学差异,但趋势与微阵列结果一致;没有反相关。所有样本中均无法测量 S100A8,可能需要使用不同的探针和引物。
本研究证实了子痫前期早孕期 FSTL3 表达减少。其他基因的非显著性趋势可能需要在具有中等或中等/大效应大小的研究中进行随访。CVS 先前微阵列的 qRT-PCR 验证可能支持子痫前期的胎盘起源假说。需要对候选基因进行复制,以作为母体-婴儿子痫前期易感性、早期检测和/或个体化治疗的潜在生物标志物。