Apolipoprotein(a) genetic sequence variants associated with systemic atherosclerosis and coronary atherosclerotic burden but not with venous thromboembolism.
African Americans/genetics; Age of Onset; Angiography; Aortic Aneurysm, Abdominal/genetics; Apolipoproteins A/genetics; Atherosclerosis/genetics; Brain Ischemia/genetics; Carotid Intima-Media Thickness; Coronary Artery Disease/genetics; European Continental Ancestry Group/genetics; Genetic Predisposition to Disease; Humans; Intracranial Aneurysm/genetics; Linear Models; Logistic Models; Myocardial Infarction/genetics; Odds Ratio; Peripheral Arterial Disease/genetics; Polymorphism, Single Nucleotide; Risk Factors; Severity of Illness Index; Stroke/genetics; Venous Thromboembolism/genetics
Abstract :
[en] 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 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.
Disciplines :
Surgery
Author, co-author :
Helgadottir, Anna
Gretarsdottir, Solveig
Thorleifsson, Gudmar
Holm, Hilma
Patel, Riyaz S.
Gudnason, Thorarinn
Jones, Gregory T.
van Rij, Andre M.
Eapen, Danny J.
Baas, Annette F.
Tregouet, David-Alexandre
Morange, Pierre-Emmanuel
Emmerich, Joseph
Lindblad, Bengt
Gottsater, Anders
Kiemeny, Lambertus A.
Lindholt, Jes S.
SakalihasanN, Natzi ; Centre Hospitalier Universitaire de Liège - CHU > Chirurgie cardio-vasculaire
Apolipoprotein(a) genetic sequence variants associated with systemic atherosclerosis and coronary atherosclerotic burden but not with venous thromboembolism.
Publication date :
2012
Journal title :
Journal of the American College of Cardiology
ISSN :
0735-1097
eISSN :
1558-3597
Publisher :
Elsevier, Netherlands
Volume :
60
Issue :
8
Pages :
722-9
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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