Document Detail


Apolipoprotein(a) genetic sequence variants associated with systemic atherosclerosis and coronary atherosclerotic burden but not with venous thromboembolism.
MedLine Citation:
PMID:  22898070     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Anna Helgadottir; Solveig Gretarsdottir; Gudmar Thorleifsson; Hilma Holm; Riyaz S Patel; Thorarinn Gudnason; Gregory T Jones; Andre M van Rij; Danny J Eapen; Annette F Baas; David-Alexandre Tregouet; Pierre-Emmanuel Morange; Joseph Emmerich; Bengt Lindblad; Anders Gottsäter; Lambertus A Kiemeny; Jes S Lindholt; Natzi Sakalihasan; Robert E Ferrell; David J Carey; James R Elmore; Philip S Tsao; Niels Grarup; Torben Jørgensen; Daniel R Witte; Torben Hansen; Oluf Pedersen; Roberto Pola; Eleonora Gaetani; Hulda B Magnadottir; Cisca Wijmenga; Gerard Tromp; Antti Ronkainen; Ynte M Ruigrok; Jan D Blankensteijn; Thomas Mueller; Philip S Wells; Javier Corral; Jose Manuel Soria; Juan Carlos Souto; John F Peden; Shapour Jalilzadeh; Bongani M Mayosi; Bernard Keavney; Rona J Strawbridge; Maria Sabater-Lleal; Karl Gertow; Damiano Baldassarre; Kristiina Nyyssönen; Rainer Rauramaa; Andries J Smit; Elmo Mannarino; Philippe Giral; Elena Tremoli; Ulf de Faire; Steve E Humphries; Anders Hamsten; Vilhelmina Haraldsdottir; Isleifur Olafsson; Magnus K Magnusson; Nilesh J Samani; Allan I Levey; Hugh S Markus; Konstantinos Kostulas; Martin Dichgans; Klaus Berger; Gregor Kuhlenbäumer; E Bernd Ringelstein; Monika Stoll; Udo Seedorf; Peter M Rothwell; Janet T Powell; Helena Kuivaniemi; Pall T Onundarson; Einar Valdimarsson; Stefan E Matthiasson; Daniel F Gudbjartsson; Guðmundur Thorgeirsson; Arshed A Quyyumi; Hugh Watkins; Martin Farrall; Unnur Thorsteinsdottir; Kari Stefansson
Publication Detail:
Type:  Journal Article; Meta-Analysis; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  60     ISSN:  1558-3597     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-17     Completed Date:  2012-10-16     Revised Date:  2014-02-24    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  722-9     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
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
Grant Support
ID/Acronym/Agency:
090532//Wellcome Trust; 095626//Wellcome Trust; 1P50HL08300/HL/NHLBI NIH HHS; 1R01HL101388/HL/NHLBI NIH HHS; HL044682/HL/NHLBI NIH HHS; HL064310/HL/NHLBI NIH HHS; NS034395/NS/NINDS NIH HHS; R01 HL064310/HL/NHLBI NIH HHS; R01HL089650-02/HL/NHLBI NIH HHS; RG/08/008/25291//British Heart Foundation; RG/08/012/25941//British Heart Foundation
Chemical
Reg. No./Substance:
0/Apolipoproteins A

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