Apolipoprotein(a) Genetic Sequence Variants Associated With Systemic Atherosclerosis and Coronary Atherosclerotic Burden But Not With Venous Thromboembolism
Por:
Helgadottir, A, Gretarsdottir, S, Thorleifsson, G, Holm, H, Patel, RS, Gudnason, T, Jones, GT, van Rij, AM, Eapen, DJ, Baas, AF, Tregouet, DA, Morange, PE, Emmerich, J, Lindblad, B, Gottsater, A, Kiemeny, LA, Lindholt, JS, Sakalihasan, N, Ferrell, RE, Carey, DJ, Elmore, JR, Tsao, PS, Grarup, N, Jorgensen, T, Witte, DR, Hansen, T, Pedersen, O, Pola, R, Gaetani, E, Magnadottir, HB, Wijmenga, C, Tromp, G, Ronkainen, A, Ruigrok, YM, Blankensteijn, JD, Mueller, T, Wells, PS, Corral, J, Soria, JM, Souto, JC, Peden, JF, Jalilzadeh, S, Mayosi, BM, Keavney, B, Strawbridge, RJ, Sabater-Lleal, M, Gertow, K, Baldassarre, D, Nyyssonen, K, Rauramaa, R, Smit, AJ, Mannarino, E, Giral, P, Tremoli, E, de Faire, U, Humphries, SE, Hamsten, A, Haraldsdottir, V, Olafsson, I, Magnusson, MK, Samani, NJ, Levey, AI, Markus, HS, Kostulas, K, Dichgans, M, Berger, K, Kuhlenbaumer, G, Ringelstein, EB, Stoll, M, Seedorf, U, Rothwell, PM, Powell, JT, Kuivaniemi, H, Onundarson, PT, Valdimarsson, E, Matthiasson, SE, Gudbjartsson, DF, Thorgeirsson, G, Quyyumi, AA, Watkins, H, Farrall, M, Thorsteinsdottir, U, Stefansson, K
Publicada:
21 ago 2012
Resumen:
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
Filiaciones:
Helgadottir, A:
DeCODE Genet, Populat Genom, IS-101 Reykjavik, Iceland
Univ Iceland, Inst Human Genet, Reykjavik, Iceland
Univ Iceland, Fac Med, Reykjavik, Iceland
Gretarsdottir, S:
DeCODE Genet, Populat Genom, IS-101 Reykjavik, Iceland
Thorleifsson, G:
DeCODE Genet, Populat Genom, IS-101 Reykjavik, Iceland
Holm, H:
DeCODE Genet, Populat Genom, IS-101 Reykjavik, Iceland
Patel, RS:
Emory Univ, Sch Med, Atlanta, GA USA
Cardiff Univ, Cardiff, S Glam, Wales
Gudnason, T:
Landspitali Univ Hosp, Dept Cardiol, Reykjavik, Iceland
Landspitali Univ Hosp, Cardiovasc Res Inst, Reykjavik, Iceland
Jones, GT:
Univ Otago, Dunedin Sch Med, Dept Surg, Otago, New Zealand
van Rij, AM:
Univ Otago, Dunedin Sch Med, Dept Surg, Otago, New Zealand
Eapen, DJ:
Emory Univ, Sch Med, Atlanta, GA USA
Baas, AF:
Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands
Tregouet, DA:
Univ Paris 06, Paris, France
ICAN Inst, INSERM UMRS 937, Paris, France
Morange, PE:
Aix Marseille Univ, Marseille, France
INSERM UMRS 1062, Marseille, France
Emmerich, J:
Univ Paris 05, Hop Europeen Georges Pompidou, INSERM UMRS 765, Med Vasc HTA, Paris, France
Lindblad, B:
Lund Univ, Dept Vasc Dis, Skane Univ Hosp, Malmo, Sweden
Gottsater, A:
Lund Univ, Dept Vasc Dis, Skane Univ Hosp, Malmo, Sweden
Kiemeny, LA:
Radboud Univ Nijmegen, Dept Epidemiol Biostat & HTA, Med Ctr, NL-6525 ED Nijmegen, Netherlands
Lindholt, JS:
Viborg Hosp, Vasc Res Unit, Viborg, Denmark
Sakalihasan, N:
Univ Hosp Liege, Liege, Belgium
Ferrell, RE:
Univ Pittsburgh, Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15260 USA
Elmore, JR:
Weis Ctr Res, Geisinger Clin, Dept Vasc Surg, Danville, PA 17822 USA
Tsao, PS:
Stanford Univ, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA
Grarup, N:
Univ Copenhagen, Fac Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark
Jorgensen, T:
Glostrup Cty Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark
Witte, DR:
Steno Diabet Ctr, DK-2820 Gentofte, Denmark
Hansen, T:
Univ Copenhagen, Fac Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark
Univ So Denmark, Odense, Denmark
Pedersen, O:
Univ Copenhagen, Fac Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark
Hagedorn Res Inst, Gentofte, Denmark
Univ Copenhagen, Inst Biomed Sci, Fac Hlth Sci, Copenhagen, Denmark
Univ Aarhus, Fac Hlth Sci, Aarhus, Denmark
Pola, R:
Catholic Univ, Lab Vasc Biol & Genet, Dept Med, A Gemelli Univ Hosp,Sch Med, Rome, Italy
Tufts Univ, Sch Med, Dept Med, Div Cardiovasc Res,Caritas St Elizabeths Med Ctr, Boston, MA 02111 USA
Gaetani, E:
Catholic Univ, Lab Vasc Biol & Genet, Dept Med, A Gemelli Univ Hosp,Sch Med, Rome, Italy
Magnadottir, HB:
Upper Valley Neurol Neurosurg, Lebanon, NH USA
Wijmenga, C:
Univ Groningen, Dept Genet, Univ Med Ctr Groningen, Groningen, Netherlands
Ronkainen, A:
Kuopio Univ Hosp, Dept Neurosurg, SF-70210 Kuopio, Finland
Ruigrok, YM:
Univ Med Ctr Utrecht, Utrecht Stroke Ctr, Dept Neurol & Neurosurg, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands
Blankensteijn, JD:
Vrije Univ Amsterdam Med Ctr, Div Surg, Amsterdam, Netherlands
Radboud Univ Nijmegen, Dept Vasc Surg, Med Ctr, NL-6525 ED Nijmegen, Netherlands
Mueller, T:
Konventhosp Barmherzige Brueder, Dept Lab Med, Linz, Austria
Wells, PS:
Univ Ottawa, Div Hematol, Ottawa Hosp, Dept Med,Res Inst, Ottawa, ON, Canada
Corral, J:
Univ Murcia, Dept Med, Ctr Reg Hemodonac, Murcia, Spain
Soria, JM:
Hosp Santa Creu i St Pau, Unit Genom Complex Dis, Res Inst, Barcelona, Spain
Souto, JC:
Hosp Santa Creu i St Pau, Haemostasis & Thrombosis Unit, Dept Haematol, Barcelona, Spain
Peden, JF:
Univ Oxford, Dept Cardiovasc Med, Wellcome Trust Ctr Human Genet, Oxford, England
Jalilzadeh, S:
Univ Oxford, Dept Cardiovasc Med, Wellcome Trust Ctr Human Genet, Oxford, England
Mayosi, BM:
Univ Cape Town, Fac Hlth Sci, ZA-7925 Cape Town, South Africa
Keavney, B:
Newcastle Univ, Inst Genet Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
Strawbridge, RJ:
Karolinska Inst, Atherosclerosis Res Unit, Dept Med Solna, Stockholm, Sweden
Sabater-Lleal, M:
Karolinska Inst, Atherosclerosis Res Unit, Dept Med Solna, Stockholm, Sweden
Gertow, K:
Karolinska Inst, Atherosclerosis Res Unit, Dept Med Solna, Stockholm, Sweden
Baldassarre, D:
Univ Milan, Dipartimento Sci Farmacol & Biomol, Ctr Cardiol Monzino, IRCCS, Milan, Italy
Nyyssonen, K:
Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland
Rauramaa, R:
Fdn Res Hlth Exercise & Nutr, Kuopio Res Inst Exercise Med, Kuopio, Finland
Smit, AJ:
Univ Med Ctr Groningen, Dept Med, NL-9713 AV Groningen, Netherlands
Mannarino, E:
Univ Perugia, Dept Clin & Expt Med, I-06100 Perugia, Italy
Giral, P:
Grp Hop Pitie Salpetriere, AP HP, Serv Endocrinol Metab, Unites Prevent Cardiovasc, Paris, France
Tremoli, E:
Univ Milan, Dipartimento Sci Farmacol & Biomol, Ctr Cardiol Monzino, IRCCS, Milan, Italy
de Faire, U:
Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, S-10401 Stockholm, Sweden
Humphries, SE:
UCL, Ctr Cardiovasc Genet, BHF Labs, Inst Cardiovasc Sci, London, England
Hamsten, A:
Karolinska Inst, Atherosclerosis Res Unit, Dept Med Solna, Stockholm, Sweden
Magnusson, MK:
Univ Iceland, Fac Med, Reykjavik, Iceland
Samani, NJ:
Univ Leicester, Dept Cardiovasc Sci, Glenfield Hosp, Clin Sci Wing, Leicester, Leics, England
St Georges Univ London, Leicester NIHR Biomed Res Unit Cardiovasc Dis, London, England
Levey, AI:
Emory Univ, Sch Med, Atlanta, GA USA
Markus, HS:
St Georges Univ London, Stroke & Dementia Res Ctr, London, England
Kostulas, K:
Karolinska Univ Hosp, Karolinska Inst, Dept Neurol, Huddinge, Sweden
Dichgans, M:
Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany
Berger, K:
Univ Munster, Inst Epidemiol & Social Med, Munster, Germany
Kuhlenbaumer, G:
Univ Kiel, Inst Expt Med, Kiel, Germany
Ringelstein, EB:
Univ Munster, Dept Neurol, D-4400 Munster, Germany
Stoll, M:
Univ Munster, Leibniz Inst Arteriosclerosis Res, Munster, Germany
Seedorf, U:
Univ Munster, Leibniz Inst Arteriosclerosis Res, Munster, Germany
Rothwell, PM:
John Radcliffe Hosp, Nuffield Dept Clin Neurosci, Oxford OX3 9DU, England
Powell, JT:
Imperial Coll Charing Cross, Vasc Surg Res Grp, London, England
Onundarson, PT:
Univ Iceland, Fac Med, Reykjavik, Iceland
Valdimarsson, E:
Landspitali Univ Hosp, Dept Neurol, Reykjavik, Iceland
Matthiasson, SE:
Laekning, Med Clin, Reykjavik, Iceland
Gudbjartsson, DF:
DeCODE Genet, Populat Genom, IS-101 Reykjavik, Iceland
Thorgeirsson, G:
Univ Iceland, Fac Med, Reykjavik, Iceland
Landspitali Univ Hosp, Dept Cardiol, Reykjavik, Iceland
Landspitali Univ Hosp, Cardiovasc Res Inst, Reykjavik, Iceland
Quyyumi, AA:
Emory Univ, Sch Med, Atlanta, GA USA
Watkins, H:
Univ Oxford, Dept Cardiovasc Med, Wellcome Trust Ctr Human Genet, Oxford, England
Farrall, M:
Univ Oxford, Dept Cardiovasc Med, Wellcome Trust Ctr Human Genet, Oxford, England
Thorsteinsdottir, U:
DeCODE Genet, Populat Genom, IS-101 Reykjavik, Iceland
Univ Iceland, Fac Med, Reykjavik, Iceland
Stefansson, K:
DeCODE Genet, Populat Genom, IS-101 Reykjavik, Iceland
Univ Iceland, Fac Med, Reykjavik, Iceland
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