Department of Epidemiology, University of Washington, Seattle, WA, USA.
BMC Pregnancy Childbirth. 2009 Dec 10;9:56. doi: 10.1186/1471-2393-9-56.
Preterm delivery (PTD) is a significant public health problem associated with greater risk of mortality and morbidity in infants and mothers. Pathophysiologic processes that may lead to PTD start early in pregnancy. We investigated early pregnancy peripheral blood global gene expression and PTD risk.
As part of a prospective study, ribonucleic acid was extracted from blood samples (collected at 16 weeks gestational age) from 14 women who had PTD (cases) and 16 women who delivered at term (controls). Gene expressions were measured using the GeneChip(R) Human Genome U133 Plus 2.0 Array. Student's T-test and fold change analysis were used to identify differentially expressed genes. We used hierarchical clustering and principle components analysis to characterize signature gene expression patterns among cases and controls. Pathway and promoter sequence analyses were used to investigate functions and functional relationships as well as regulatory regions of differentially expressed genes.
A total of 209 genes, including potential candidate genes (e.g. PTGDS, prostaglandin D2 synthase 21 kDa), were differentially expressed. A set of these genes achieved accurate pre-diagnostic separation of cases and controls. These genes participate in functions related to immune system and inflammation, organ development, metabolism (lipid, carbohydrate and amino acid) and cell signaling. Binding sites of putative transcription factors such as EGR1 (early growth response 1), TFAP2A (transcription factor AP2A), Sp1 (specificity protein 1) and Sp3 (specificity protein 3) were over represented in promoter regions of differentially expressed genes. Real-time PCR confirmed microarray expression measurements of selected genes.
PTD is associated with maternal early pregnancy peripheral blood gene expression changes. Maternal early pregnancy peripheral blood gene expression patterns may be useful for better understanding of PTD pathophysiology and PTD risk prediction.
早产（PTD）是一个重大的公共卫生问题，与母婴死亡率和发病率增加有关。可能导致 PTD 的病理生理过程早在妊娠早期就开始了。我们研究了早期妊娠外周血全基因表达与 PTD 风险。
作为一项前瞻性研究的一部分，从 14 名早产（病例）和 16 名足月分娩（对照）的妇女的 16 周妊娠龄血液样本中提取核糖核酸。使用 GeneChip(R) Human Genome U133 Plus 2.0 Array 测量基因表达。使用学生 t 检验和倍数变化分析来识别差异表达基因。我们使用层次聚类和主成分分析来描述病例和对照组之间的特征基因表达模式。通路和启动子序列分析用于研究差异表达基因的功能和功能关系以及调节区域。
总共鉴定出 209 个基因，包括潜在的候选基因（如 PTGDS、前列腺素 D2 合酶 21kDa），这些基因存在差异表达。其中一组基因可以准确地对病例和对照组进行预诊断分离。这些基因参与与免疫系统和炎症、器官发育、代谢（脂质、碳水化合物和氨基酸）和细胞信号转导相关的功能。潜在转录因子如 EGR1（早期生长反应 1）、TFAP2A（转录因子 AP2A）、Sp1（特异性蛋白 1）和 Sp3（特异性蛋白 3）的结合位点在差异表达基因的启动子区域中过度表达。实时 PCR 证实了所选基因的微阵列表达测量。
PTD 与母亲早期妊娠外周血基因表达变化有关。母亲早期妊娠外周血基因表达模式可能有助于更好地理解 PTD 的病理生理学和 PTD 风险预测。
