Apolipoprotein(a) Genetic Sequence Variants Associated With Systemic Atherosclerosis and Coronary Atherosclerotic Burden But Not With Venous Thromboembolism

被引：153

作者：

Helgadottir, Anna ^{[1
,2
,3
]}

Gretarsdottir, Solveig ^{[1
]}

Thorleifsson, Gudmar ^{[1
]}

Holm, Hilma ^{[1
]}

Patel, Riyaz S. ^{[4
,5
]}

Gudnason, Thorarinn ^{[6
,7
]}

Jones, Gregory T. ^{[8
]}

van Rij, Andre M. ^{[8
]}

Eapen, Danny J. ^{[4
]}

Baas, Annette F. ^{[9
]}

Tregouet, David-Alexandre ^{[10
,11
]}

Morange, Pierre-Emmanuel ^{[12
,13
]}

Emmerich, Joseph ^{[14
]}

Lindblad, Bengt ^{[15
]}

Gottsater, Anders ^{[15
]}

Kiemeny, Lambertus A. ^{[16
]}

Lindholt, Jes S. ^{[17
]}

Sakalihasan, Natzi ^{[18
]}

Ferrell, Robert E. ^{[19
]}

Carey, David J.

Elmore, James R. ^{[20
]}

Tsao, Philip S. ^{[21
]}

Grarup, Niels ^{[22
]}

Jorgensen, Torben ^{[23
]}

Witte, Daniel R. ^{[24
]}

Hansen, Torben ^{[22
,25
]}

Pedersen, Oluf ^{[22
,26
,27
,28
]}

Pola, Roberto ^{[29
,30
]}

Gaetani, Eleonora ^{[29
]}

Magnadottir, Hulda B. ^{[31
]}

Wijmenga, Cisca ^{[32
]}

Tromp, Gerard

Ronkainen, Antti ^{[33
]}

Ruigrok, Ynte M. ^{[34
]}

Blankensteijn, Jan D. ^{[35
,36
]}

Mueller, Thomas ^{[37
]}

Wells, Philip S. ^{[38
]}

Corral, Javier ^{[39
]}

Manuel Soria, Jose ^{[40
]}

Carlos Souto, Juan ^{[41
]}

Peden, John F. ^{[42
]}

Jalilzadeh, Shapour ^{[42
]}

Mayosi, Bongani M. ^{[43
]}

Keavney, Bernard ^{[44
]}

Strawbridge, Rona J. ^{[45
]}

Sabater-Lleal, Maria ^{[45
]}

Gertow, Karl ^{[45
]}

Baldassarre, Damiano ^{[46
]}

Nyyssonen, Kristiina ^{[47
]}

Rauramaa, Rainer ^{[48
]}

机构：

[1] DeCODE Genet, Populat Genom, IS-101 Reykjavik, Iceland

[2] Univ Iceland, Inst Human Genet, Reykjavik, Iceland

[3] Univ Iceland, Fac Med, Reykjavik, Iceland

[4] Emory Univ, Sch Med, Atlanta, GA USA

[5] Cardiff Univ, Cardiff, S Glam, Wales

[6] Landspitali Univ Hosp, Dept Cardiol, Reykjavik, Iceland

[7] Landspitali Univ Hosp, Cardiovasc Res Inst, Reykjavik, Iceland

[8] Univ Otago, Dunedin Sch Med, Dept Surg, Otago, New Zealand

[9] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands

[10] Univ Paris 06, Paris, France

[11] ICAN Inst, INSERM UMRS 937, Paris, France

[12] Aix Marseille Univ, Marseille, France

[13] INSERM UMRS 1062, Marseille, France

[14] Univ Paris 05, Hop Europeen Georges Pompidou, INSERM UMRS 765, Med Vasc HTA, Paris, France

[15] Lund Univ, Dept Vasc Dis, Skane Univ Hosp, Malmo, Sweden

[16] Radboud Univ Nijmegen, Dept Epidemiol Biostat & HTA, Med Ctr, NL-6525 ED Nijmegen, Netherlands

[17] Viborg Hosp, Vasc Res Unit, Viborg, Denmark

[18] Univ Hosp Liege, Liege, Belgium

[19] Univ Pittsburgh, Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15260 USA

[20] Weis Ctr Res, Geisinger Clin, Dept Vasc Surg, Danville, PA 17822 USA

[21] Stanford Univ, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA

[22] Univ Copenhagen, Fac Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark

[23] Glostrup Cty Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark

[24] Steno Diabet Ctr, DK-2820 Gentofte, Denmark

[25] Univ So Denmark, Odense, Denmark

[26] Hagedorn Res Inst, Gentofte, Denmark

[27] Univ Copenhagen, Inst Biomed Sci, Fac Hlth Sci, Copenhagen, Denmark

[28] Univ Aarhus, Fac Hlth Sci, Aarhus, Denmark

[29] Catholic Univ, Lab Vasc Biol & Genet, Dept Med, A Gemelli Univ Hosp,Sch Med, Rome, Italy

[30] Tufts Univ, Sch Med, Dept Med, Div Cardiovasc Res,Caritas St Elizabeths Med Ctr, Boston, MA 02111 USA

[31] Upper Valley Neurol Neurosurg, Lebanon, NH USA

[32] Univ Groningen, Dept Genet, Univ Med Ctr Groningen, Groningen, Netherlands

[33] Kuopio Univ Hosp, Dept Neurosurg, SF-70210 Kuopio, Finland

[34] Univ Med Ctr Utrecht, Utrecht Stroke Ctr, Dept Neurol & Neurosurg, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands

[35] Vrije Univ Amsterdam Med Ctr, Div Surg, Amsterdam, Netherlands

[36] Radboud Univ Nijmegen, Dept Vasc Surg, Med Ctr, NL-6525 ED Nijmegen, Netherlands

[37] Konventhosp Barmherzige Brueder, Dept Lab Med, Linz, Austria

[38] Univ Ottawa, Div Hematol, Ottawa Hosp, Dept Med,Res Inst, Ottawa, ON, Canada

[39] Univ Murcia, Dept Med, Ctr Reg Hemodonac, Murcia, Spain

[40] Hosp Santa Creu i St Pau, Unit Genom Complex Dis, Res Inst, Barcelona, Spain

[41] Hosp Santa Creu i St Pau, Haemostasis & Thrombosis Unit, Dept Haematol, Barcelona, Spain

[42] Univ Oxford, Dept Cardiovasc Med, Wellcome Trust Ctr Human Genet, Oxford, England

[43] Univ Cape Town, Fac Hlth Sci, ZA-7925 Cape Town, South Africa

[44] Newcastle Univ, Inst Genet Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England

[45] Karolinska Inst, Atherosclerosis Res Unit, Dept Med Solna, Stockholm, Sweden

[46] Univ Milan, Dipartimento Sci Farmacol & Biomol, Ctr Cardiol Monzino, IRCCS, Milan, Italy

[47] Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland

[48] Fdn Res Hlth Exercise & Nutr, Kuopio Res Inst Exercise Med, Kuopio, Finland

[49] Univ Med Ctr Groningen, Dept Med, NL-9713 AV Groningen, Netherlands

[50] Univ Perugia, Dept Clin & Expt Med, I-06100 Perugia, Italy

来源：

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY | 2012年 / 60卷 / 08期

基金：

美国国家卫生研究院; 芬兰科学院; 英国惠康基金; 瑞典研究理事会;

关键词：

association; atherosclerosis; genetic; lipoprotein(a); thrombosis; INTIMA-MEDIA THICKNESS; PERIPHERAL ARTERIAL-DISEASE; RISK-FACTORS; VASCULAR-DISEASE; MYOCARDIAL-INFARCTION; ISCHEMIC-STROKE; LIPOPROTEIN(A); SEVERITY; WOMEN; METAANALYSIS;

D O I：

10.1016/j.jacc.2012.01.078

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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

引用

页码：722 / 729

页数：8

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