DNA METHYLATION AND GENE EXPRESSION PROFILES IN MONOCYTES

单核细胞中的 DNA 甲基化和基因表达谱

• 批准号: 8167061
• 负责人: YONGMEI LIU
• 金额: $ 1.1万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167061
• 关键词: Aberrant DNA Methylation; Atherosclerosis; Blood; Computer Retrieval of Information on Scientific Projects Database; DNA; DNA Methylation; DNA Sequence; Data; Environment; Environmental Risk Factor; Epigenetic Process; Extramural Activities; Funding; Gene Expression; Genetic; Goals; Grant; Individual; Institution; Joints; Mediating; Methylation; Molecular Profiling; Morbidity - disease rate; Pathogenesis; Peripheral Blood Mononuclear Cell; Pilot Projects; Play; Protocols documentation; RNA; Research; Research Personnel; Resources; Risk; Role; Source; United States National Institutes of Health; Variant; atherogenesis; cardiovascular disorder risk; clinical phenotype; monocyte; mortality

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. Atherosclerotic vascular disease remains one of the leading causes of morbidity and mortality worldwide. It is widely accepted that individual variation in the risk for cardiovascular disease results from the joint effects of both environmental and genetic factors. Considerable progress has been made in identifying specific environmental factors. In contrast, only a few DNA sequence variants have been identified that are clearly associated with risk for atherosclerotic vascular disease, and the apparent effects of these variants are modest. Epigenetic phenomenon such as DNA methylation represent another class of genetic factors that may be modified by the environment which have the ability to influence clinical phenotypes such as atherosclerosis. We hypothesize that alterations in DNA methylation profiles in monocytes play a causative role in atherogenesis, mediated through altering gene expression profiles. We postulate that aberrant DNA methylation may contribute to the pathogenesis of atherosclerosis. We plan to develop a protocol to reliably isolate monocyte DNA and RNA in order to identify variations of DNA methylation and gene expression. Briefly, we plan to 1) isolate Peripheral Blood Mononuclear Cell (PBMCs) from a routine blood draw, 2) isolate monocytes from the PBMCs, 3) extract DNA and RNA simultaneously from the monocytes, and 4) quantify DNA methylation and gene expression levels from monocytes. The overall goal of this pilot study is to generate preliminary data to be used for an additional NIH extramural R01 application.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 动脉粥样硬化性血管疾病仍然是全世界发病和死亡的主要原因之一。人们普遍认为，心血管疾病风险的个体差异是环境和遗传因素共同影响的结果。在确定具体环境因素方面已经取得了相当大的进展。相比之下，只有少数 DNA 序列变异已被发现与动脉粥样硬化性血管疾病的风险明显相关，而且这些变异的明显影响不大。 DNA甲基化等表观遗传现象代表了另一类可能被环境改变的遗传因素，能够影响动脉粥样硬化等临床表型。我们假设单核细胞 DNA 甲基化谱的改变在动脉粥样硬化形成中发挥致病作用，通过改变基因表达谱介导。我们推测异常的 DNA 甲基化可能导致动脉粥样硬化的发病机制。我们计划开发一种可靠分离单核细胞 DNA 和 RNA 的方案，以便识别 DNA 甲基化和基因表达的变化。简而言之，我们计划 1) 从常规抽血中分离外周血单核细胞 (PBMC)，2) 从 PBMC 中分离单核细胞，3) 从单核细胞中同时提取 DNA 和 RNA，4) 定量 DNA 甲基化和基因表达水平来自单核细胞。该试点研究的总体目标是生成用于额外 NIH 外部 R01 应用的初步数据。