University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON, K1Y 4W7, Canada.
J Cardiovasc Transl Res. 2008 Mar;1(1):11-6. doi: 10.1007/s12265-007-9001-1. Epub 2008 Jan 26.
Personalized medicine is defined as individualized treatment based on the individual's genetic variants. Such treatment has the potential to enable pharmacogenetics, such as the prevention of 100,000 deaths per year in the USA because of adverse drug reactions or specify treatment in heart failure such at the beta 1 adrenergic receptor polymorphisms. It is claimed that coronary artery disease (CAD) is at least 50% because of genetic predisposition. Identification of the genes predisposing to CAD would greatly facilitate prevention, early treatment, and more specific therapies. The arrival of the multimillion single nucleotide polymorphism (SNP) array provides the high throughput genotyping required to perform genome-wide Association (GWA) studies. These studies require markers (SNPs) at intervals of 6,000 bp and sample size of several thousands. Platforms are available to genotype and process millions of genotypes per day. The GWA performed by the Ottawa Heart Genomic Study identified the first deoxyribonucleic acid region (9p21) predisposing to CAD after replication in six independent populations totaling 23,000. This was subsequently confirmed in several independent studies totally more than 45,000 individuals. The region confers a risk for CAD independent of known risk factors. 9p21 occurs in heterozygous form in 40 to 50% of Caucasians with increased risk of 15 to 20% and in homozygous form in 25% of Caucasians with increased risk of 40%. Identification of the genes predisposing to CAD is a prerequisite for personalized care of these patients. It is anticipated that most of the genes predisposing to CAD will be identified in the next 5 to 8 years. The 9p21, in addition to conferring increased risk, provides the bonus of being independent of known risk factors. Thus, 9p21 is likely to provide the impetus and nidus for a major research effort over the next few years. It has the potential to not only provide for early genetic screening but also as a target for novel therapy.
个体化医学被定义为基于个体遗传变异的个体化治疗。这种治疗有可能实现药物遗传学，例如，由于药物不良反应，每年可预防美国 10 万人死亡，或指定心力衰竭β 1 肾上腺素能受体多态性的治疗。据称，冠心病（CAD）至少有 50%是由于遗传易感性。鉴定导致 CAD 的基因将极大地促进预防、早期治疗和更具体的治疗。数百万个单核苷酸多态性（SNP）阵列的出现提供了进行全基因组关联（GWA）研究所需的高通量基因分型。这些研究需要间隔 6000bp 的标记物（SNP）和几千个样本量。有平台可以每天对数百万个基因型进行基因分型和处理。渥太华心脏基因组学研究进行的 GWA 在六个独立的总人数为 23000 人的人群中复制后，确定了第一个导致 CAD 的脱氧核糖核酸区域（9p21）。随后在几个独立的研究中得到了证实，总人数超过 45000 人。该区域独立于已知的危险因素赋予 CAD 的风险。9p21 在 40%至 50%的白种人中以杂合形式出现，风险增加 15%至 20%，在 25%的白种人中以纯合形式出现，风险增加 40%。鉴定导致 CAD 的基因是对这些患者进行个性化护理的前提。预计在未来 5 到 8 年内，大多数导致 CAD 的基因将被鉴定出来。9p21 不仅增加了风险，而且还具有独立于已知危险因素的优势。因此，9p21 很可能在未来几年内为一项重大研究提供动力和核心。它不仅有可能进行早期基因筛查，而且还可能成为新疗法的靶点。
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