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早发型重度子痫前期母血基因表达谱分析:新型生物标志物的鉴定。

Gene expression profiling of maternal blood in early onset severe preeclampsia: identification of novel biomarkers.

机构信息

Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, PR China.

出版信息

J Perinat Med. 2009;37(6):609-16. doi: 10.1515/JPM.2009.103.

Abstract

AIMS

To investigate candidate genes in peripheral blood mononuclear cell (PBMC) that are associated with early onset severe preeclampsia (ES-PE) and to describe candidate genes function using microarrays and real-time polymerase chain reaction (PCR).

METHODS

PBMC RNA was extracted from six patients with ES-PE and five uncomplicated pregnancies. The HG_U133 plus 2.0 Affymetrix GeneChips that represented 47,000 genes were used to measure gene expression in each sample. Significance analysis of microarray identified potential signature genes characterizing ES-PE vs. uncomplicated pregnancies. Eight genes were selected for confirmation by real-time PCR of 32 patients with ES-PE and 24 uncomplicated pregnancies, matched for maternal age, parity, race and gestational weeks.

RESULTS

Using a whole-genome approach to study the molecular determinants of ES-PE, 72 genes were found to be differentially expressed between cases and controls, including 38 up-regulated genes and 34 down-regulated genes in the group of ES-PE. Killer cell immunoglobulin-like receptor, three domains, long cytoplasmic tail, 2 (KIR3DL2), aldo-keto reductase family 1, member C3 (AKR1C3), churchill domain containing 1 (CHURC1), and solute carrier family 25, member 13 (SLC25A13) were validated to be down-regulated in the patients with ES-PE by real-time PCR.

CONCLUSIONS

Expression of genes with diverse function is associated with ES-PE risk, providing opportunities for the development of non-invasive diagnosis.

摘要

目的

研究与早发型重度子痫前期(ES-PE)相关的外周血单个核细胞(PBMC)中的候选基因,并使用微阵列和实时聚合酶链反应(PCR)描述候选基因的功能。

方法

从 6 例 ES-PE 患者和 5 例非复杂妊娠患者中提取 PBMC RNA。使用代表 47,000 个基因的 HG_U133 plus 2.0 Affymetrix GeneChips 测量每个样本中的基因表达。微阵列的显著性分析确定了潜在的特征基因,这些基因可将 ES-PE 与非复杂妊娠区分开来。选择 8 个基因通过实时 PCR 在 32 例 ES-PE 患者和 24 例非复杂妊娠患者中进行验证,这些患者的母亲年龄、产次、种族和妊娠周数相匹配。

结果

使用全基因组方法研究 ES-PE 的分子决定因素,发现 72 个基因在病例组和对照组之间表达差异,其中 ES-PE 组有 38 个上调基因和 34 个下调基因。杀伤细胞免疫球蛋白样受体,三个结构域,长胞质尾,2(KIR3DL2),醛酮还原酶家族 1,成员 C3(AKR1C3),丘吉尔结构域包含 1(CHURC1)和溶质载体家族 25,成员 13(SLC25A13)通过实时 PCR 验证在 ES-PE 患者中下调。

结论

具有不同功能的基因表达与 ES-PE 风险相关,为非侵入性诊断的发展提供了机会。

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