Variations in discovery-based preeclampsia candidate genes.

Variations in discovery-based preeclampsia candidate genes.
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DOI:
10.1111/j.1752-8062.2012.00413.x
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发表时间:
2012-08
期刊:
Clinical and translational science
影响因子:
--
通讯作者:
Lyons-Weiler J
Lyons-Weiler J
中科院分区:
其他
文献类型:
--
作者:
Founds SA;Shi H;Conley YP;Jeyabalan A;Roberts JM;Lyons-Weiler J

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先兆子痫是一种常见的和潜在的致命的妊娠障碍与终身心血管疾病的风险增加的幸存者。我们先前的全球基因表达微阵列分析导致了一组新的36名候选人在孕早期胎盘的妇女谁随后发展先兆子痫。在这份报告中,我们提出了初步的研究表明,在这些候选基因的一个子集,在母体白细胞和胎儿胎盘DNA的28例和27个对照二联体的基因型和甲基化变异的生物标志物。我们使用MassArray iPLEX检测了84个单核苷酸多态性(SNP),使用EpiTYPER检测了50个CpG位点。通过使用Fisher精确检验(p≤0.05)选择的25个SNP和根据倍数变化选择的20个CpG位点鉴定有希望的预测建模。基因型分布分析确定了9个配对病例与配对对照之间不同的SNP变异。这些发现验证了所检查的候选基因,并支持进一步开发生物标志物的方法的可行性。实施的综合方法开始将36个候选者转化为临床实用性,作为先兆子痫的筛查方式。
Preeclampsia is a common and potentially lethal pregnancy disorder with lifelong increased risk of cardiovascular disease in survivors. Our prior global gene expression microarray analysis led to a novel set of 36 candidates in first trimester placentas of women who subsequently developed preeclampsia. In this report, we present preliminary studies demonstrating biomarkers of genotype and methylation variations in a subset of these candidate genes in maternal leukocyte and fetoplacental DNA of 28 case and 27 control dyads. We tested 84 single nucleotide polymorphisms (SNPs) using MassArray iPLEX and 50 CpG sites using EpiTYPER assays. Promising prediction modeling was identified with 25 SNPs selected using Fisher's exact tests (p≤0.05) and 20 CpG sites selected on fold change. Genotype Distribution Analysis identified SNP variations that differed between 9 paired cases versus paired controls. The findings validate the examined candidate genes and support feasibility of methods for further biomarker development. The integrative approach that was implemented begins to translate the 36 candidates toward clinical utility as a screening modality for preeclampsia.
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