Apolipoprotein(a) Genetic Sequence Variants Associated With Systemic Atherosclerosis and Coronary Atherosclerotic Burden But Not With Venous Thromboembolism
Apolipoprotein(a) Genetic Sequence Variants Associated With Systemic Atherosclerosis and Coronary Atherosclerotic Burden But Not With Venous Thromboembolism
复制标题
DOI：
10.1016/j.jacc.2012.01.078
复制
发表时间：
2012-08-21
影响因子：
24
通讯作者：
Stefansson, Kari
中科院分区：
文献类型：
--
作者：
Helgadottir, Anna;Gretarsdottir, Solveig;Stefansson, Kari
目的探讨载脂蛋白(a)基因（LPA）变异对不同动脉粥样硬化和血栓形成成分的血管疾病的影响。目前尚不清楚与脂蛋白(a)水平和冠状动脉疾病（CAD）相关的LPA变异rs10455872和rs3798220是否主要通过动脉粥样硬化或血栓导致易感性。方法将2种LPA变异组合起来，作为LPA评分与缺血性卒中（以及TOAST [Trial of Org 10172 in Acute stroke Treatment]亚型）的关联进行检验（有效样本量[n(e)] = 9396）；外周动脉疾病（n(e) = 5,215）；腹主动脉瘤（ne = 4,572）；静脉血栓栓塞（ne = 4607）；颅内动脉瘤（ne = 1,328）；CAD （n(e) = 12,716）、颈动脉内膜-中膜厚度（n = 3,714）和血管造影CAD严重程度（n = 5,588）。结果LPA评分与缺血性卒中亚型大动脉粥样硬化（比值比[OR]: 1.27; p = 6.7 × 10(-4)）、外周动脉疾病（比值比[OR]: 1.47; p = 2.9 × 10(-14)）、腹主动脉瘤（比值比：1.23;p = 6.0 × 10(-5)）相关，但与缺血性卒中亚型心脏栓塞（比值比：1.03;p = 0.69）或小血管疾病（比值比：1.06;p = 0.52）无关。尽管LPA变异与颈动脉内膜-中膜厚度无关，但它们与冠状动脉阻塞的数量相关（p = 4.8 x 10(-12)）。此外，携带LPA危险变异的冠心病患者对冠状动脉树外动脉粥样硬化表现的易感性增加（OR: 1.26; p = 0.0010），并且与不携带危险变异的冠心病患者相比，冠心病发病时间更早（-1.58年/等位基因；p = 8.2 x 10(-8)）。LPA评分与静脉血栓栓塞（OR: 0.97; p = 0.63）或颅内动脉瘤（OR: 0.85; p = 0.15）无相关性。结论：LPA序列变异与动脉粥样硬化负荷相关，但与主要的血栓表型无关。[J]中华医学会心脏科杂志，2012;32 (3):391 - 391
Objectives The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene (LPA) on vascular diseases with different atherosclerotic and thrombotic components.Background It is unclear whether the LPA variants rs10455872 and rs3798220, which correlate with lipoprotein(a) levels and coronary artery disease (CAD), confer susceptibility predominantly via atherosclerosis or thrombosis.Methods The 2 LPA variants were combined and examined as LPA scores for the association with ischemic stroke (and TOAST [Trial of Org 10172 in Acute Stroke Treatment] subtypes) (effective sample size [n(e)] = 9,396); peripheral arterial disease (n(e) = 5,215); abdominal aortic aneurysm (ne = 4,572); venous thromboembolism (ne = 4,607); intracranial aneurysm (ne = 1,328); CAD (n(e) = 12,716), carotid intima-media thickness (n = 3,714), and angiographic CAD severity (n = 5,588). Results LPA score was associated with ischemic stroke subtype large artery atherosclerosis (odds ratio [OR]: 1.27; p = 6.7 X 10(-4)), peripheral artery disease (OR: 1.47; p = 2.9 x 10(-14)), and abdominal aortic aneurysm (OR: 1.23; p = 6.0 x 10(-5)), but not with the ischemic stroke subtypes cardioembolism (OR: 1.03; p = 0.69) or small vessel disease (OR: 1.06; p = 0.52). Although the LPA variants were not associated with carotid intima-media thickness, they were associated with the number of obstructed coronary vessels (p = 4.8 x 10(-12)). Furthermore, CAD cases carrying LPA risk variants had increased susceptibility to atherosclerotic manifestations outside of the coronary tree (OR: 1.26; p = 0.0010) and had earlier onset of CAD (-1.58 years/allele; p = 8.2 x 10(-8)) than CAD cases not carrying the risk variants. There was no association of LPA score with venous thromboembolism (OR: 0.97; p = 0.63) or intracranial aneurysm (OR: 0.85; p = 0.15).Conclusions LPA sequence variants were associated with atherosclerotic burden, but not with primarily thrombotic phenotypes. (J Am Coll Cardiol 2012; 60: 722-9) (C) 2012 by the American College of Cardiology Foundation