载脂蛋白(a)遗传序列变异与全身性动脉粥样硬化和冠状动脉粥样硬化负担相关，但与静脉血栓栓塞无关。

Apolipoprotein(a) genetic sequence variants associated with systemic atherosclerosis and coronary atherosclerotic burden but not with venous thromboembolism.

机构信息

Population Genomics, deCODE Genetics, Reykjavik, Iceland.

出版信息

J Am Coll Cardiol. 2012 Aug 21;60(8):722-9. doi: 10.1016/j.jacc.2012.01.078.

DOI:10.1016/j.jacc.2012.01.078

PMID:22898070

Abstract

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 (n(e) = 4,572); venous thromboembolism (n(e) = 4,607); intracranial aneurysm (n(e) = 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 × 10(-4)), peripheral artery disease (OR: 1.47; p = 2.9 × 10(-14)), and abdominal aortic aneurysm (OR: 1.23; p = 6.0 × 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 × 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 × 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.

摘要

目的

本研究旨在探讨载脂蛋白(a)基因（LPA）变异与不同动脉粥样硬化和血栓形成成分的血管疾病之间的关系。

背景

目前尚不清楚与脂蛋白(a)水平和冠心病（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形成导致易感性。

方法

将这 2 个 LPA 变异组合为 LPA 评分，以研究其与缺血性卒中（和 TOAST [急性卒中治疗组织 10172 试验]亚型）（有效样本量[n(e)]=9396）、外周动脉疾病（n(e)=5215）、腹主动脉瘤（n(e)=4572）、静脉血栓栓塞症（n(e)=4607）、颅内动脉瘤（n(e)=1328）、CAD（n(e)=12716）、颈动脉内膜中层厚度（n=3714）和血管造影 CAD 严重程度（n=5588）之间的关系。

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（OR：1.47；p=2.9×10(-14)）和腹主动脉瘤（OR：1.23；p=6.0×10(-5)）相关，但与缺血性卒中亚型心源性栓塞（OR：1.03；p=0.69）或小血管疾病（OR：1.06；p=0.52）无关。尽管 LPA 变异与颈动脉内膜中层厚度无关，但与阻塞冠状动脉数量相关（p=4.8×10(-12)）。此外，携带 LPA 风险变异的 CAD 病例对冠状动脉树外的动脉粥样硬化表现具有更高的易感性（OR：1.26；p=0.0010），并且发病年龄更早（每个等位基因-1.58 年；p=8.2×10(-8)）。LPA 评分与静脉血栓栓塞症（OR：0.97；p=0.63）或颅内动脉瘤（OR：0.85；p=0.15）之间没有关联。