Genetic analysis of carotid artery intima-media thickness (IMT)

遗传因素在动脉粥样硬化及其主要临床表现、心肌梗死和中风的发生发展中起重要作用。为了确定以前未知的基因参与动脉粥样硬化的发展，我们建议研究颈总动脉内膜中层厚度（IMT）作为一个中间表型。在本项目的准备中，我们招募了156个核心家庭，包括一个明显动脉粥样硬化的索引患者，他/她的伴侣和他们共同的后代。从颈动脉粥样硬化进展研究（CAPS）中获得了大量基于人群的独立受试者样本，该项目的主要目标是确定一个或多个与颈总动脉IMT显著相关的染色体位点。为此，我们计划在可用的家族样本中进行全基因组连锁扫描。同时，我们会把家庭样本扩大至300个核心家庭。第二个目标是评估最有希望的染色体区域中候选基因的遗传变异与IMT的关联。这些研究将在CAPS样本中进行。

Genetic factors strongly contribute to the development of atherosclerosis and its major clinical manifestations, myocardial infarction and stroke. To identify previously unknown genes that are involved in the development of atherosclerosis we propose to study common carotid artery intima-media thickness (IMT) as an intermediate phenotype. In preparation of the present project we recruited 156 nuclear families, consisting of an index patient with manifest atherosclerosis, his/her partner and their common offspring. Access to a large population-based sample of independent subjects derived from the Carotid Atherosclerosis Progression Study (CAPS) was established.The primary goal of this project is to identify one or more chromosomal loci with significant linkage to common carotid artery IMT. To this end, we plan to perform a genome-wide linkage scan in the available family sample. In parallel, we will enlarge the family sample to 300 nuclear families. The second goal is to evaluate the association of genetic variants of candidate genes in the most promising chromosomal region with IMT. These studies will be done in the CAPS sample.