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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 早产（在37周之前）发生在所有怀孕的大约10-12％中，并且在过去几十年中，这种发生率没有发生显着变化。 尽管围产期和新生儿护理的进步和改善，但早产仍然是围产期发病率和死亡率的最重要原因。 我们降低早产风险的努力最关键的局限性是对“过早”激活的信号转导途径的理解不足。 此外，多种病因和缺乏充分模仿人类妊娠和分娩的动物模型阻碍了该领域的进步。 药理学剂（例如溶症）的使用来调节子宫收缩或使用抗生素尚未成功。 几条证据，例如增强风险以及细胞因子中的早产史和多态性的史，支持了自发性早产和出生的遗传易感性。 人类基因组序列和系统方法的生物学和医学方法的可用性有望在未来几年将其从反应性学科（患者病后反应）转变为一种预测，个性化和预防性模式。 这将是通过使用血液来鉴定与疾病状态临床前发作相关的分子特征的早期诊断来部分实现的。 表观遗传网络的平衡（组蛋白尾巴修饰和DNA甲基化）的平衡已与包括癌症在内的几种主要病变有关。 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，已经证明表观遗传改变在劳动的开始中起着关键作用。 尽管已经描述了直到胚泡阶段的早期人类胚胎的全球DNA甲基化变化，但在人妊娠的每个三个月中，胎盘中发生的表观遗传变化尚无信息。 该建议将检验以下假设：由启动子高甲基化沉默的特定基因调节了不同的调节途径，这些途径导致这些基因的启动子区域的早产和甲基化DNA可以预测对早产和分娩易感的女性。