DIAGNOSTIC MARKERS FOR EARLY DETECTION AND TREATMENT OF PRETERM PREGNANCIES

早孕早期检测和治疗的诊断标志物

• 批准号: 7604876
• 负责人: ANUJA DOKRAS
• 金额: $ 3.62万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7604876
• 关键词: Aberrant DNA Methylation; Animal Model; Antibiotics; Biology; Birth; Blood; Caring; Clinical; Computer Retrieval of Information on Scientific Projects Database; DNA; DNA Methylation; Detection; Diagnostic; Discipline; Disease; Disruption; Early Diagnosis; Embryo; Epigenetic Process; Equilibrium; Etiology; Funding; Gene Silencing; Genes; Genetic Polymorphism; Genetic Predisposition to Disease; Grant; Histones; Human; Hypermethylation; Incidence; Institution; Labor Onset; Lead; Malignant Neoplasms; Medicine; Modification; Molecular Profiling; Morbidity - disease rate; Neonatal; Onset of illness; Pathology; Patients; Perinatal; Placenta; Play; Pregnancy; Premature Birth; Premature Labor; Preventive; Promoter Regions; Recording of previous events; Regulatory Pathway; Research; Research Personnel; Resources; Risk; Role; Signal Transduction Pathway; Source; Staging; System; Tail; Testing; Tocolytic Agents; United States National Institutes of Health; Uterine Contraction; Week; Woman; blastocyst; cytokine; genome sequencing; mortality; pre-clinical; promoter

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Preterm delivery (before 37 weeks) occurs in approximately 10-12% of all pregnancies and this incidence has not changed significantly over the past few decades. Despite the advances and improvements in perinatal and neonatal care, preterm delivery is still the most important cause of perinatal morbidity and mortality. The most critical limitation in our efforts to decrease this risk of preterm delivery is inadequate understanding of the signal transduction pathways that are 'prematurely' activated. Moreover, multiple etiologies and a lack of an animal model that adequately mimics human gestation and parturition have impeded progress in this field. The use of pharmacological agents such as tocolytics to modulate uterine contractions or the use of antibiotics has not been successful. Several lines of evidence such as increased risk with a history of preterm delivery and polymorphisms in cytokines support a genetic predisposition to spontaneous preterm labor and birth. The availability of the human genome sequence and systems approach to biology and medicine promises to transform the practice of medicine over the next few years moving it from reactive discipline (responding after patient is sick) to a predictive, personalized and preventive mode. This will be achieved, in part, by early diagnostics using blood to identify molecular signatures associated with the pre-clinical onset of disease state. The disruption of balance of epigenetic networks (histone tail modifications and DNA methylation) has been implicated in several major pathologies including cancer. Aberrant DNA methylation can be detected in blood before clinical detection of the disease state. Recently, epigenetic alterations have been shown to play a critical role in the onset of labor. Although global DNA methylation changes in early human embryos up to the blastocyst stage have been described, there is no information on epigenetic changes occurring in the placenta during each trimester of human gestation. This proposal will test the hypothesis that specific genes silenced by promoter hypermethylation modulate distinct regulatory pathways that lead to preterm deliveries and methylated DNA in the promoter regions of these genes can predict women who are susceptible to preterm labor and delivery.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 早产（37周之前）发生在所有妊娠的大约10-12%，并且在过去几十年中，该发生率没有显著变化。 尽管在围产期和新生儿护理方面取得了进展和改善，但早产仍然是围产期发病率和死亡率的最重要原因。 我们努力降低早产风险的最关键限制是对“过早”激活的信号转导通路的理解不足。 此外，多种病因学和缺乏充分模拟人类妊娠和分娩的动物模型阻碍了这一领域的进展。 使用药物如宫缩抑制剂来调节子宫收缩或使用抗生素尚未成功。 有多条证据支持自发性早产和分娩的遗传易感性，如有早产史的风险增加和细胞因子多态性。 人类基因组序列的可用性和生物学和医学的系统方法有望在未来几年内改变医学实践，将其从反应性学科（在患者生病后做出反应）转变为预测性，个性化和预防性模式。 这将部分地通过使用血液的早期诊断来实现，以识别与疾病状态的临床前发作相关的分子特征。 表观遗传网络（组蛋白尾部修饰和DNA甲基化）平衡的破坏与包括癌症在内的几种主要病理学有关。 在临床检测疾病状态之前，可以在血液中检测到异常的DNA甲基化。 最近，表观遗传学改变已被证明在分娩的发生中起着关键作用。 尽管已经描述了早期人类胚胎直至囊胚阶段的整体DNA甲基化变化，但没有关于人类妊娠每个三个月期间胎盘中发生的表观遗传变化的信息。 这项提案将测试这一假设，即启动子超甲基化沉默的特定基因调节不同的调控途径，导致早产和甲基化的DNA在这些基因的启动子区域可以预测妇女谁是容易早产和分娩。