Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
Indian J Med Res. 2010 Nov;132(5):567-78.
Coronary artery disease (CAD) is a leading cause of death and disability worldwide. In addition to lifestyle and environmental factors which are major aetiologic determinants, there is considerable familial clustering of the disease indicating a genetic component in its causation. Although the total genetic contribution to CAD risk can be quantified, the determination of the size and number of contributing effects is impossible without identifying all CAD susceptibility genes. However, despite extensive studies, strong evidence of a molecular genetic association with coronary artery disease or myocardial infarction remains elusive. Genome wide association studies have been successful in identifying robust associations of single nucleotide polymorphisms (SNP) with CAD. Identifying the causal variant and dissecting pathways linking these variants to disease process is a major challenge. Technologies from whole genome sequencing, proteomics, transcriptomics and metabolomics are now available to extend analysis to a more complete range of potential susceptibility variants, and to support more explicit modelling of the joint effects of genes and environment. The availability of these high throughput technologies does not diminish the importance of rigorous phenotyping and appropriate study designs in all the endeavours to understand the aetiopathogenesis of CAD. Combining classical epidemiology with modern genomics will require collaborative efforts within the cardiovascular disease community at both bench and bedside and this will have the potential to expand our understanding of CAD and translate discoveries into clinically useful applications that will have a major impact on public health.
冠心病（CAD）是全球范围内导致死亡和残疾的主要原因。除了生活方式和环境因素等主要病因决定因素外，该病还存在明显的家族聚集性，表明其发病机制中存在遗传成分。尽管可以定量评估 CAD 风险的总遗传贡献，但如果不能确定所有 CAD 易感基因，则无法确定其影响的大小和数量。然而，尽管进行了广泛的研究，但仍未能找到与冠心病或心肌梗死有明确分子遗传学关联的证据。全基因组关联研究已成功鉴定出单核苷酸多态性（SNP）与 CAD 的稳健关联。确定致病变异体并剖析将这些变异体与疾病过程联系起来的途径是一个主要挑战。全基因组测序、蛋白质组学、转录组学和代谢组学等技术的出现，使我们能够将分析扩展到更广泛的潜在易感变异体范围，并更明确地对基因和环境的联合效应进行建模。这些高通量技术的出现并没有降低在所有努力中严格表型分析和适当研究设计的重要性，这些努力旨在了解 CAD 的病因发病机制。将经典流行病学与现代基因组学相结合，需要心血管疾病领域在实验室和临床两方面的合作，这将有可能扩展我们对 CAD 的理解，并将发现转化为具有重大公共卫生影响的临床有用应用。
