DNA METHYLATION AND GENE EXPRESSION PROFILES IN MONOCYTES

Wake Forest University Health Sciences, Winston-Salem NC

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Abstract

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.