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Lp-PLA(2), scavenge...
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Manichaikul, AniUniv Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA;Univ Virginia, Dept Publ Hlth Sci, Biostat Sect, Charlottesville, VA USA
(författare)
Lp-PLA(2), scavenger receptor class B type I gene (SCARB1) rs10846744 variant, and cardiovascular disease
- Artikel/kapitelEngelska2018
Förlag, utgivningsår, omfång ...
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2018-10-05
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PUBLIC LIBRARY SCIENCE,2018
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electronicrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:uu-368449
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-368449URI
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https://doi.org/10.1371/journal.pone.0204352DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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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.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Wang, Xin-QunUniv Virginia, Dept Publ Hlth Sci, Biostat Sect, Charlottesville, VA USA
(författare)
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Li, LiPAREXEL Int, Genom Med, Durham, NC USA
(författare)
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Erdmann, JeanetteUniv Lubeck, Inst Integrat & Expt Genom, Lubeck, Germany;DZHK German Res Ctr Cardiovasc Res, Partner Site Hamburg, Lubeck, Germany
(författare)
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Lettre, GuillaumeMontreal Heart Inst, Montreal, PQ, Canada;Univ Montreal, Montreal, PQ, Canada
(författare)
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Bis, Joshua C.Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA;Univ Washington, Dept Med, Seattle, WA USA
(författare)
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Waterworth, DawnGlaxoSmithKline, Genet, King Of Prussia, PA USA
(författare)
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Cushman, MaryUniv Vermont, Dept Med, Burlington, VT USA;Univ Vermont, Dept Pathol & Lab Med, Burlington, VT USA
(författare)
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Jenny, Nancy S.Univ Vermont, Dept Pathol & Lab Med, Burlington, VT USA
(författare)
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Post, Wendy S.Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA;Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA
(författare)
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Palmas, WalterColumbia Univ, Coll Phys & Surg, Dept Med, Div Gen Med, New York, NY USA
(författare)
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Tsai, Michael Y.Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA
(författare)
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Wallentin, Lars,1943-Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Kardiologi(Swepub:uu)larswall
(författare)
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White, HarveyAuckland City Hosp Green Lane Cardiovasc Sci, Auckland, New Zealand
(författare)
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Schunkert, HeribertDZHK German Res Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany;Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany
(författare)
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O'Donnell, Christopher J.Boston Vet Adm Healthcare, Cardiol Sect, Boston, MA USA;NHLBI, Framingham, MA USA;Boston Univ Framingham Heart Study, Framingham, MA USA
(författare)
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Herrington, David M.Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Winston Salem, NC 27103 USA
(författare)
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Rich, Stephen S.Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA;Univ Virginia, Dept Publ Hlth Sci, Biostat Sect, Charlottesville, VA USA
(författare)
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O'Donoghue, Michelle L.Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA
(författare)
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Rodriguez, AnnabelleUniv Connecticut Hlth, Dept Cell Biol, Ctr Vasc Biol, Farmington, CT 06030 USA
(författare)
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Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA;Univ Virginia, Dept Publ Hlth Sci, Biostat Sect, Charlottesville, VA USAUniv Virginia, Dept Publ Hlth Sci, Biostat Sect, Charlottesville, VA USA
(creator_code:org_t)
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Ingår i:PLOS ONE: PUBLIC LIBRARY SCIENCE13:101932-6203
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- Av författaren/redakt...
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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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visa fler...
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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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