Robarts Research Institute, University of Western Ontario, London, Canada.
Crit Rev Clin Lab Sci. 2009;46(5-6):343-60. doi: 10.3109/07388550903422075.
Coronary artery disease (CAD) is an inflammatory-metabolic disease in which atherosclerotic plaques cause stenosis of the coronary arteries, leading to acute clinical complications such as myocardial infarction. Since CAD is a multifactorial, polygenic disease with a substantial environmental component, individual risk prediction and stratification is often difficult. Recent technological advances have resulted in substantial progress elucidating the impact of common genetic variation on CAD progression. The discovery of common genetic variants, including the chromosome 9p21.3 locus as the strongest and most highly replicated independent genetic CAD risk factor, has stimulated interest in genetic testing for CAD-associated risk variants. The ultimate goal of genotype-based CAD risk prediction is to improve upon the discrimination and stratification offered by conventional risk factors alone. Genotype-based CAD risk prediction may eventually have clinical utility, but not without intrinsic complexities. Are genotype variables superior predictors of risk compared to a family history of CAD? Is a 10-year risk prediction window ambitious enough for the predictive power of genotype data? This review will outline the current state of genotype-based CAD risk prediction and highlight challenging issues integral to the successful implementation of genetic testing for CAD.
冠状动脉疾病 (CAD) 是一种炎症代谢性疾病，其中动脉粥样硬化斑块导致冠状动脉狭窄，导致急性临床并发症，如心肌梗死。由于 CAD 是一种多因素、多基因疾病，具有很大的环境成分，因此个体风险预测和分层通常很困难。最近的技术进步在阐明常见遗传变异对 CAD 进展的影响方面取得了重大进展。常见遗传变异的发现，包括染色体 9p21.3 位点作为最强和最高度复制的独立遗传 CAD 风险因素，激发了对与 CAD 相关的风险变异进行遗传检测的兴趣。基于基因型的 CAD 风险预测的最终目标是提高传统风险因素单独提供的区分度和分层。基于基因型的 CAD 风险预测最终可能具有临床实用性，但并非没有内在的复杂性。与 CAD 的家族史相比，基因型变量是否是更好的风险预测指标？10 年风险预测窗口对于基因型数据的预测能力来说是否过于雄心勃勃？本文将概述基于基因型的 CAD 风险预测的现状，并强调成功实施 CAD 遗传检测所必需的具有挑战性的问题。
