Polymorphisms in hypoxia inducible factor 1 and the initial clinical presentation of coronary disease
Polymorphisms in hypoxia inducible factor 1 and the initial clinical presentation of coronary disease
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DOI：
10.1016/j.ahj.2007.07.042
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发表时间：
2007-12-01
影响因子：
4.8
通讯作者：
Go, Alan S.
中科院分区：
文献类型：
--
作者：
Hlatky, Mark A.;Quertermous, Thomas;Go, Alan S.
只有部分冠状动脉疾病（CAD）患者发生急性心肌梗死（MI），新的证据表明MI的易感性在患者中存在系统性差异，可能具有遗传成分。本研究的目的是评估是否在基因编码的基因多态性介导的反应缺血影响潜在的CAD患者心肌梗死的脆弱性。方法我们前瞻性地确定患者在他们的初始临床表现CAD的时间有急性心肌梗死或稳定劳力型心绞痛。结果与466例稳定型心绞痛患者相比，急性心肌梗死患者中男性、吸烟者和高血压患者的比例明显增高，而β受体阻滞剂和他汀类药物的使用比例明显降低。HIF 1A的三种多态性（Pro582 Ser，rs 11549465; rs 1087314;和Thr 41 8 Ile，rs 41508050）在稳定劳力型心绞痛而非急性MI的住院患者中显著更常见，即使在对心脏危险因素和药物进行统计学校正后。HIF-介导的转录活性显着降低时，HIF-1A空成纤维细胞转染变异HIFIA等位基因比野生型HIF-1A等位基因。结论HIF-1A的多态性与发展稳定劳力型心绞痛，而不是急性心肌梗死作为CAD的初始临床表现。
Background Only some patients with coronary artery disease (CAD) develop acute myocardial infarction (MI), and emerging evidence suggests vulnerability to MI varies systematically among patients and may have a genetic component. The goal of this study was to assess whether polymorphisms in genes encoding elements of pathways mediating the response to ischemia affect vulnerability to MI among patients with underlying CAD.Methods We prospectively identified patients at the time of their initial clinical presentation of CAD who had either an acute MI or stable exertional angina. We collected clinical data and genotyped 34 polymorphisms in 6 genes (ANGPT1, HIF1A, THBS1, VEGFA, VEGFC, VEGFR2).Results The 909 patients with acute MI were significantly more likely than the 466 patients with stable angina to be male, current smokers, and hypertensive, and less likely to be taking beta-blockers or statins. Three polymorphisms in HIF1A (Pro582Ser, rs 11549465; rs 1087314; and Thr41 8 Ile, rs41508050) were significantly more common inpatients who presented with stable exertional angina rather than acute MI, even after statistical adjustment for cardiac risk factors and medications. The HIF-mediated transcriptional activity was significantly lower when HIF1A null fibroblasts were transfected with variant HIFI A alleles than with wild-type HIF1A alleles.Conclusions Polymorphisms in HIF1A were associated with development of stable exertional angina rather than acute MI as the initial clinical presentation of CAD.