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。 动脉粥样硬化血管疾病仍然是全球发病率和死亡率的主要原因之一。人们普遍认为，心血管疾病风险的个体变异是由于环境和遗传因素的共同影响而产生的。在确定特定的环境因素方面取得了长足的进步。相比之下，只有几个DNA序列变体显然与动脉粥样硬化血管疾病的风险有关，这些变体的明显影响是适度的。表观遗传现象（例如DNA甲基化）代表了另一种可能由环境改变的遗传因素，这些因素可能会影响临床表型，例如动脉粥样硬化。我们假设单核细胞中DNA甲基化谱的变化在动脉粥样硬化中起因果作用，这是通过改变基因表达谱而介导的。我们假设异常的DNA甲基化可能有助于动脉粥样硬化的发病机理。我们计划开发一种可靠分离单核细胞DNA和RNA的方案，以鉴定DNA甲基化和基因表达的变化。简而言之，我们计划1）从常规血液抽血中分离出外周血单核细胞（PBMC），2）从PBMC中分离单核细胞，3）从单核细胞中提取DNA和RNA，并从单核细胞中提取DNA和RNA，以及4）量化DNA甲基化和基因表达水平，从单核细胞中提取DNA和基因表达水平。这项试验研究的总体目标是生成初步数据，用于额外的NIH壁外R01应用。