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Lp-PLA(2), scavenge...
Lp-PLA(2), scavenger receptor class B type I gene (SCARB1) rs10846744 variant, and cardiovascular disease
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- Manichaikul, Ani (author)
- Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA;Univ Virginia, Dept Publ Hlth Sci, Biostat Sect, Charlottesville, VA USA
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- Wang, Xin-Qun (author)
- Univ Virginia, Dept Publ Hlth Sci, Biostat Sect, Charlottesville, VA USA
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- Li, Li (author)
- PAREXEL Int, Genom Med, Durham, NC USA
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- Erdmann, Jeanette (author)
- Univ Lubeck, Inst Integrat & Expt Genom, Lubeck, Germany;DZHK German Res Ctr Cardiovasc Res, Partner Site Hamburg, Lubeck, Germany
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- Lettre, Guillaume (author)
- Montreal Heart Inst, Montreal, PQ, Canada;Univ Montreal, Montreal, PQ, Canada
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- Bis, Joshua C. (author)
- Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA;Univ Washington, Dept Med, Seattle, WA USA
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- Waterworth, Dawn (author)
- GlaxoSmithKline, Genet, King Of Prussia, PA USA
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- Cushman, Mary (author)
- Univ Vermont, Dept Med, Burlington, VT USA;Univ Vermont, Dept Pathol & Lab Med, Burlington, VT USA
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- Jenny, Nancy S. (author)
- Univ Vermont, Dept Pathol & Lab Med, Burlington, VT USA
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- Post, Wendy S. (author)
- Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA;Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA
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- Palmas, Walter (author)
- Columbia Univ, Coll Phys & Surg, Dept Med, Div Gen Med, New York, NY USA
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- Tsai, Michael Y. (author)
- Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA
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- Wallentin, Lars, 1943- (author)
- Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Kardiologi
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- White, Harvey (author)
- Auckland City Hosp Green Lane Cardiovasc Sci, Auckland, New Zealand
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- Schunkert, Heribert (author)
- DZHK German Res Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany;Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany
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- O'Donnell, Christopher J. (author)
- Boston Vet Adm Healthcare, Cardiol Sect, Boston, MA USA;NHLBI, Framingham, MA USA;Boston Univ Framingham Heart Study, Framingham, MA USA
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- Herrington, David M. (author)
- Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Winston Salem, NC 27103 USA
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- Rich, Stephen S. (author)
- Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA;Univ Virginia, Dept Publ Hlth Sci, Biostat Sect, Charlottesville, VA USA
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- O'Donoghue, Michelle L. (author)
- Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA
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- Rodriguez, Annabelle (author)
- Univ Connecticut Hlth, Dept Cell Biol, Ctr Vasc Biol, Farmington, CT 06030 USA
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(creator_code:org_t)
- 2018-10-05
- 2018
- English.
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In: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 13:10
- Related links:
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https://doi.org/10.1...
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Abstract
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- Background We previously reported association of SCARB1 SNP rs10846744 with common carotid IMT (cIMT) and cardiovascular disease (CVD) events. Since rs10846744 has been reported in association with Lp-PLA(2) mass and activity, we hypothesized that inflammatory pathways might mediate the association of rs10846744 with atherosclerosis. Methods We first examined association of rs10846744 in CVD in multiple large-scale consortium-based genome-wide association studies. We further examined 27 parameters of interest, including Lp-PLA(2) mass and activity, inflammatory markers, and plasma phospholipid fatty acids, and fatty acid ratios in participants from the Multi-Ethnic Study of Atherosclerosis (MESA), as potential mediators in the pathway linking rs10846744 with cIMT and incident CVD. Finally, we examined the association of rs10846744 with Lp-PLA(2) activity, cardiovascular outcomes, and interaction with the Lp-PLA(2) inhibitor, darapladib, in the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy (STABILITY) and Stabilization of Plaque using Darapladib-Thrombolysis in Myocardial Infarction 52 (SOLID-TIMI 52) studies. Results SCARB1 rs10846744 was associated with coronary artery disease events in CARDIo-GRAMplusC4D (odds ratio 1.05; 95% CI [1.02, 1.07]; P= 1.4x10(-4)). In combined analysis across race/ethnic groups in MESA, rs10846744 was associated with Lp-PLA(2 )mass (P= 0.04) and activity (P = 0.001), homocysteine (P = 0.03), LDL particle number (P = 0.01), docosahexaenoic acid [DHA] (P = 0.01), docosapentaenoic acid [DPA] (P = 0.04), DPA/eicosapentaenoic acid [EPA] ratio (P= 0.002), and DHA/EPA ratio (P= 0.008). Lp-PLA(2) activity was identified as a mediator of rs10846744 with cIMT in a basic model (P = 8x10(-5)), but not after adjustment for CVD risk factors. There was no interaction or modifier effect of the Lp-PLA(2) inhibitor darapladib assignment on the relationship between rs10846744 and major CVD events in either STABILITY or SOLID-TIMI 52. Summary SCARB1 rs10846744 is significantly associated with Lp-PLA(2) activity, atherosclerosis, and CVD events, but Lp-PLA(2) activity is not a mediator in the association of rs10846744 with cIMT in MESA.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
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- art (subject category)
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- By the author/editor
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Manichaikul, Ani
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Wang, Xin-Qun
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Li, Li
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Erdmann, Jeanett ...
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Lettre, Guillaum ...
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Bis, Joshua C.
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Waterworth, Dawn
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Cushman, Mary
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Jenny, Nancy S.
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Post, Wendy S.
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Palmas, Walter
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Tsai, Michael Y.
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Wallentin, Lars, ...
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White, Harvey
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Schunkert, Herib ...
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O'Donnell, Chris ...
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Herrington, Davi ...
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Rich, Stephen S.
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O'Donoghue, Mich ...
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Rodriguez, Annab ...
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- MEDICAL AND HEALTH SCIENCES
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PLOS ONE
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Uppsala University