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- PMID: 22898070
- UKPMCID: 22898070
- DOI: 10.1016/j.jacc.2012.01.078
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Apolipoprotein(a) genetic sequence variants associated with systemic atherosclerosis and coronary atherosclerotic burden but not with venous thromboembolism.
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; Gottsäter, Anders; Kiemeny, Lambertus A; Lindholt, Jes S; Sakalihasan, Natzi; Ferrell, Robert E; Carey, David J; Elmore, James R; Tsao, Philip S; Grarup, Niels; Jørgensen, Torben; Witte, Daniel R; Hansen, Torben; Pedersen, Oluf; Pola, Roberto; Gaetani, Eleonora; Magnadottir, Hulda B; Wijmenga, Cisca; Tromp, Gerard; Ronkainen, Antti; Ruigrok, Ynte M; Blankensteijn, Jan D; Mueller, Thomas; Wells, Philip S; Corral, Javier; Soria, Jose Manuel; Souto, Juan Carlos; Peden, John F; Jalilzadeh, Shapour; Mayosi, Bongani M; Keavney, Bernard; Strawbridge, Rona J; Sabater-Lleal, Maria; Gertow, Karl; Baldassarre, Damiano; Nyyssönen, Kristiina; Rauramaa, Rainer; Smit, Andries J; Mannarino, Elmo; Giral, Philippe; Tremoli, Elena; de Faire, Ulf; Humphries, Steve E; Hamsten, Anders; Haraldsdottir, Vilhelmina; Olafsson, Isleifur; Magnusson, Magnus K; Samani, Nilesh J; Levey, Allan I; Markus, Hugh S; Kostulas, Konstantinos; Dichgans, Martin; Berger, Klaus; Kuhlenbäumer, Gregor; Ringelstein, E Bernd; Stoll, Monika; Seedorf, Udo; Rothwell, Peter M; Powell, Janet T; Kuivaniemi, Helena; Onundarson, Pall T; Valdimarsson, Einar; Matthiasson, Stefan E; Gudbjartsson, Daniel F; Thorgeirsson, Guðmundur; Quyyumi, Arshed A; Watkins, Hugh; Farrall, Martin; Thorsteinsdottir, Unnur; Stefansson, Kari
Journal of the American College of Cardiology. 2012;60(8):722-9.
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Full-text held externally
- PMID: 22898070
- UKPMCID: 22898070
- DOI: 10.1016/j.jacc.2012.01.078
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 Ă— 10(-4)), peripheral artery disease (OR: 1.47; p = 2.9 Ă— 10(-14)), and abdominal aortic aneurysm (OR: 1.23; p = 6.0 Ă— 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 Ă— 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 Ă— 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.
Bibliographic metadata
- 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
- Gottsäter, Anders
- Kiemeny, Lambertus A
- Lindholt, Jes S
- Sakalihasan, Natzi
- Ferrell, Robert E
- Carey, David J
- Elmore, James R
- Tsao, Philip S
- Grarup, Niels
- Jørgensen, Torben
- Witte, Daniel R
- Hansen, Torben
- Pedersen, Oluf
- Pola, Roberto
- Gaetani, Eleonora
- Magnadottir, Hulda B
- Wijmenga, Cisca
- Tromp, Gerard
- Ronkainen, Antti
- Ruigrok, Ynte M
- Blankensteijn, Jan D
- Mueller, Thomas
- Wells, Philip S
- Corral, Javier
- Soria, Jose Manuel
- Souto, Juan Carlos
- Peden, John F
- Jalilzadeh, Shapour
- Mayosi, Bongani M
- Keavney, Bernard
- Strawbridge, Rona J
- Sabater-Lleal, Maria
- Gertow, Karl
- Baldassarre, Damiano
- Nyyssönen, Kristiina
- Rauramaa, Rainer
- Smit, Andries J
- Mannarino, Elmo
- Giral, Philippe
- Tremoli, Elena
- de Faire, Ulf
- Humphries, Steve E
- Hamsten, Anders
- Haraldsdottir, Vilhelmina
- Olafsson, Isleifur
- Magnusson, Magnus K
- Samani, Nilesh J
- Levey, Allan I
- Markus, Hugh S
- Kostulas, Konstantinos
- Dichgans, Martin
- Berger, Klaus
- Kuhlenbäumer, Gregor
- Ringelstein, E Bernd
- Stoll, Monika
- Seedorf, Udo
- Rothwell, Peter M
- Powell, Janet T
- Kuivaniemi, Helena
- Onundarson, Pall T
- Valdimarsson, Einar
- Matthiasson, Stefan E
- Gudbjartsson, Daniel F
- Thorgeirsson, GuĂ°mundur
- Quyyumi, Arshed A
- Watkins, Hugh
- Farrall, Martin
- Thorsteinsdottir, Unnur
- Stefansson, Kari