Cardiovascular Division, Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri 63110, USA; email:
Department of Genetics, Washington University School of Medicine, Saint Louis, Missouri 63110, USA.
Annu Rev Med. 2019 Jan 27;70:19-32. doi: 10.1146/annurev-med-041717-085853. Epub 2018 Oct 24.
Coronary artery disease (CAD) is a major cause of morbidity and mortality. Unfortunately, despite decades of research focused on disease pathogenesis, we still lack a sufficient pharmacopeia for preventing CAD. The failure of many novel cardiovascular drugs to improve clinical outcomes reflects the major substantial challenge of drug development: identifying causal mechanisms that can be therapeutically manipulated to lower disease risk. Identifying genetic variants that are associated with risk of CAD has emerged as a clear path toward improving our understanding of the underlying mechanisms that lead to disease and to the development of new therapies. Here, we review the potential utility and limitations of using human genetics to guide the identification of therapeutic targets for CAD.
冠心病（CAD）是发病率和死亡率的主要原因。不幸的是，尽管几十年来我们一直专注于研究疾病的发病机制，但我们仍然缺乏预防 CAD 的充分药物。许多新型心血管药物未能改善临床结果，这反映了药物开发的主要实质性挑战：确定可通过治疗手段加以控制以降低疾病风险的因果机制。确定与 CAD 风险相关的遗传变异已成为一种明确的途径，可以帮助我们更好地了解导致疾病的潜在机制，并开发新的治疗方法。在这里，我们回顾了利用人类遗传学来指导 CAD 治疗靶点识别的潜在效用和局限性。
