Genomics in coronary artery disease: Past, present and future
Genomics in coronary artery disease: Past, present and future
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DOI：
10.1016/s0828-282x(10)71064-3
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发表时间：
2010-03-01
影响因子：
6.2
通讯作者：
Roberts, Robert
中科院分区：
文献类型：
--
作者：
Dandona, Sonny;Stewart, Alexandre F. R.;Roberts, Robert
在过去的三年里，已经完成了一系列全基因组关联研究，旨在确定与冠状动脉疾病(CAD)或其相关表型-心肌梗死(NIL)的风险相关的基因变异。第一个也是最强大的遗传风险变异位于染色体9p21.3上。一系列其他基因座，其患病率较低，人群归因风险较小，被描述为与CAD/MI有关。然而，这些基因座只解释了CAD/MIA可遗传成分的一小部分。这些基因座中的一小部分改变了已知参与动脉粥样硬化和/或血栓形成的基因的功能。其余的似乎没有通过任何已知的风险因素传递风险，这意味着尚不清楚的致病途径。此外，包括9p21在内的许多基因座位于基因间隔区，通过新的机制引起表型，这些机制的阐明将极有可能揭开新的治疗靶点。未来的研究将集中在定义影响表型的潜在机制，这些遗传标记在标准风险预测模型中的作用，以及寻找更多的基因座来解释“缺失的遗传性”。
The past three years has seen the completion of a series of genome-wide association studies designed to identify genetic variants associated with risk for coronary artery disease (CAD) or its related phenotype, myocardial infarction (Nil). The first and most robust genetic risk variant is located on chromosome 9p21.3. A series of other loci, with less prevalence and smaller population-attributable risks, were described to associate with CAD/MI. However, these loci explain only a fraction of the heritable component of CAD/MIA small fraction of these loci alter the function of genes known to be involved in atherogenesis and/or thrombosis. The rest do not appear to impart their risk via any known risk factors, implying yet unknown pathogenetic pathways. Moreover, many loci, including 9p21, are located in intergenic segments and elicit the phenotype by novel mechanisms whose elucidation will most likely unravel novel therapeutic targets.Future investigation will be focused on defining the underlying mechanism by which the phenotype is affected, the role of these genetic markers in standard risk prediction models and identification of further loci to explain the 'missing heritability'.