Roberts Robert
Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
Curr Opin Cardiol. 2008 Nov;23(6):629-33. doi: 10.1097/HCO.0b013e32830e6b4e.
To review the evidence supporting genetic predisposition to coronary artery disease (CAD). Secondly, to elucidate the barriers precluding the identification of genes responsible for CAD. Thirdly, to indicate the new technology now available to overcome these barriers and summarize current progress.
Evidence strongly supports that 50% of susceptibility to CAD is genetic. Prevention of CAD requires comprehensive genetic and risk factor modification. Technology to perform genome-wide association studies became available in 2005, namely, the microarrays with 500,000 and 1 million single nucleotide polymorphisms as DNA markers for high-throughput genotyping to determine gene frequencies in large datasets of cases and controls. The first genetic variant, 9p21, for CAD was identified in the Ottawa Heart Genomic study. This is not only a genetic risk factor but also independent of other known risk factors for CAD. 9p21 was subsequently confirmed as a risk variant in several other independent studies involving 64 000 Caucasians. 9p21 increases the risk of CAD by 40% and 20% in heterozygous or homozygous forms respectively. It occurs in 75% of Caucasians, and has recently been confirmed in several other ethnic groups.
Thus, identification of predisposition to CAD is well underway with genome-wide association studies and the first common genetic risk variant, 9p21, has been identified.
回顾支持冠状动脉疾病（CAD）遗传易感性的证据。其次，阐明阻碍识别CAD相关基因的障碍。第三，指出目前可用于克服这些障碍的新技术并总结当前进展。
有强有力的证据支持，CAD易感性的50%是由遗传因素导致的。预防CAD需要综合进行基因和风险因素的调整。2005年出现了可用于进行全基因组关联研究的技术，即带有50万和100万个单核苷酸多态性的微阵列，作为DNA标记用于高通量基因分型，以确定病例和对照的大型数据集中的基因频率。在渥太华心脏基因组研究中首次发现了CAD的第一个遗传变异9p21。这不仅是一个遗传风险因素，而且独立于CAD的其他已知风险因素。9p21随后在其他几项涉及64000名高加索人的独立研究中被确认为风险变异。9p21分别以杂合子或纯合子形式使CAD风险增加40%和20%。它在75%的高加索人中出现，最近在其他几个种族群体中也得到了证实。
因此，通过全基因组关联研究，对CAD易感性的识别正在顺利进行，并且已经识别出第一个常见的遗传风险变异9p21。
