Advances in the genetic basis of coronary artery disease.
Advances in the genetic basis of coronary artery disease.
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DOI：
10.1007/s11883-005-0012-6
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发表时间：
2005-05-01
影响因子：
5.8
通讯作者：
Wang, Qing
中科院分区：
文献类型：
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作者：
Wang, Qing
近年来，冠状动脉疾病（CAD）、心肌梗死（MI）和缺血性卒中的遗传学研究取得了令人兴奋的进展。MEF2A基因位于染色体15q26.3，是一个在冠状动脉内皮细胞中高表达的转录因子，是冠心病和心肌梗死的致病基因。大约1%至2%的CAD患者可能携带MEF2A突变。利用全基因组关联研究或全基因组连锁研究，已经确定了四个新的易感基因：LTA（编码细胞因子α-光氧素-α）; LGALS 2（编码半乳糖凝集素-2，一种LTA相互作用蛋白）在22q12-q13上用于MI; ALOX5AP（编码5-脂氧合酶激活蛋白，参与合成有效的促炎性白三烯）在13q12 - 13上用于MI和中风; PDE4D（编码磷酸二酯酶4D）定位于5q12，用于缺血性卒中。这些研究确定了CAD发病机制的新机制，即血管内皮的肌细胞增强因子2（MEF2）信号通路，并证实了炎症在疾病过程中的作用。
Exciting advances have been made recently in genetic studies of coronary artery disease (CAD), myocardial infarction (MI), and ischemic stroke. One disease-causing gene for CAD and MI has been identified as MEF2A, which is located on chromosome 15q26.3 and encodes a transcriptional factor with a high level of expression in coronary endothelium. Approximately 1% to 2% of CAD patients may carry an MEF2A mutation. Four new susceptibility genes have been identified using genome-wide association studies or genome-wide linkage studies: LTA (encoding cytokine lymphotoxin-alpha) on 6p21.3 for MI; LGALS2 (encoding galectin-2, an LTA-interacting protein) on 22q12-q13 for MI; ALOX5AP (encoding 5-lipoxygenase activating protein involved in synthesizing potent pro-inflammatory leukotrienes) on 13q12-13 for MI and stroke; and PDE4D (encoding phosphodiesterase 4D) on 5q12 for ischemic stroke. These studies identify a new mechanism, the myocyte enhancer factor 2 (MEF2) signaling pathway of vascular endothelium, for the pathogenesis of CAD, and also confirm the role of inflammation in the disease process.