Molecular Genetics of Caronary Artery Disease

描述（由申请人提供）：冠状动脉疾病（CAD）是最常见的心脏病。它影响了近1300万美国人，是美国的主要死亡原因。这种疾病与心血管系统的老化、环境攻击和遗传易感性密切相关。这种多因素疾病是阐明相关遗传变异以及转录和表观遗传影响变化的良好模型。更好地了解CAD中涉及的分子因子的复杂相互作用将有助于定义导致疾病易感性、形成和进展的分子标记。该培训计划将通过对早发性CAD连锁区域进行基于家族的关联分析，并通过应用高分辨率基因组微阵列实验来确定与CAD相关的DNA甲基化模式和转录因子结合，从而确定导致CAD的分子因素。阵列工作主要集中在两个组成部分，(1)确定整个人类基因组中的GATA2 DNA结合位点，(2)鉴定增殖的主动脉平滑肌细胞中的DNA甲基化模式。

DESCRIPTION (provided by applicant): Coronary Artery Disease (CAD) is the most common form of heart disease. It affects nearly 13 million Americans and is the leading cause of death in the United States. The disease is intimately linked to the aging of the cardiovascular system, environmental assault, and genetic predisposition. This multifactorial disease is an excellent model to elucidate associated genetic variation and the impact of changes in transcription and epigenetic influences. A better understanding of the complex interplay of the molecular factors involved in CAD will help to define molecular markers that lead to disease predisposition, formation, and progression. This training proposal will identify molecular factors that lead to CAD using family based association analysis of early onset CAD linkage regions and through the application of high-resolution genomic microarray experiments to determine DNA methylation patterns and transcription factor binding associated with CAD. The array work focuses on two components, (1) defining GATA2 DNA binding sites across the human genome and (2) identifying DNA methylation patterns in proliferating aortic smooth muscle cells.