Center for Human Genetic Research and Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02108, USA.
Annu Rev Genomics Hum Genet. 2010;11:91-108. doi: 10.1146/annurev-genom-082509-141637.
Coronary artery disease and its clinical manifestations, including myocardial infarction, are heritable traits, consistent with a role for inherited DNA sequence variation in conferring risk for disease. Knowledge of the new sequence variations in the genome that confer risk has the potential to illuminate new causal biologic pathways in humans and to thereby further improve diagnosis and treatment. Here, we review recent progress in mapping genetic loci related to coronary disease and risk factor phenotypes, including plasma lipoprotein concentrations. Genome-wide linkage (in families) and association (in populations) studies have identified more than a dozen genetic loci related to coronary disease. A key challenge now is to move from mapping loci to pinpointing causal genes and variants, and to develop a molecular understanding of how these genes lead to coronary disease.
冠状动脉疾病及其临床表现,包括心肌梗死,是可遗传的特征,这与遗传 DNA 序列变异在赋予疾病风险方面的作用一致。了解赋予风险的新基因组序列变异有可能阐明人类新的因果生物学途径,从而进一步改善诊断和治疗。在这里,我们回顾了与冠状动脉疾病和风险因素表型(包括血浆脂蛋白浓度)相关的遗传位点作图的最新进展。全基因组连锁(在家庭中)和关联(在人群中)研究已经确定了十多个与冠状动脉疾病相关的遗传位点。现在的一个关键挑战是从定位位点转移到确定因果基因和变异,并从分子水平理解这些基因如何导致冠状动脉疾病。