Evidence map›Paper›PMID 30289950›Full record

Trial reportPloS one2018

Lp-PLA2, scavenger receptor class B type I gene (SCARB1) rs10846744 variant, and cardiovascular disease.

Ani Manichaikul, Xin-Qun Wang, Li Li, Jeanette Erdmann, Guillaume Lettre, Joshua C Bis, Dawn Waterworth, Mary Cushman, Nancy S Jenny, Wendy S Post and 10 more

Open access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 26% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 16 institutions in 5 countries.

Ani ManichaikulCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, United States of America.
Xin-Qun WangDepartment of Public Health Sciences, Biostatistics Section, University of Virginia, Charlottesville, VA, United States of America.
Li LiGenomic Medicine, PAREXEL International, Durham, NC, United States of America.
Jeanette ErdmannInstitut für Integrative und Experimentelle Genomik, University of Lübeck, Lübeck, Germany.
Guillaume LettreMontreal Heart Institute, Montreal, Quebec, Canada.
Joshua C BisCardiovascular Health Research Unit, University of Washington, Seattle, WA, United States of America.
Dawn WaterworthGenetics, GlaxoSmithKline, King of Prussia, PA, United States of America.
Mary CushmanDepartment of Medicine, University of Vermont, Burlington, VT, United States of America.
Nancy S JennyDepartment of Pathology and Laboratory Medicine, University of Vermont, Burlington, VT, United States of America.
Wendy S PostDivision of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine and Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America.
Walter PalmasDivision of General Medicine, Department of Medicine, Columbia University College of Physicians & Surgeons, New York, NY, United States of America.
Michael Y TsaiDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, United States of America.ORCID 0000-0001-7553-3408
Lars WallentinUppsala Clinical Research Center and Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Harvey WhiteAuckland City Hospital Green Lane Cardiovascular Sciences, Auckland, New Zealand.
Heribert SchunkertDZHK (German Research Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.ORCID 0000-0001-6428-3001
Christopher J O'DonnellCardiology Section, Boston Veteran's Administration Healthcare, Boston, MA, United States of America.
David M HerringtonDepartment of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, United States of America.
Stephen S RichCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, United States of America.
Michelle L O'DonoghueTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston MA, United States of America.
Annabelle RodriguezDepartment of Cell Biology, Center for Vascular Biology, University of Connecticut Health, Farmington, CT, United States of America.ORCID 0000-0002-3917-8565
University of Virginia · USUniversity of Vermont · USAuckland City Hospital · NZBrigham and Women's Hospital · USColumbia University · USGerman Centre for Cardiovascular Research · DEGlaxoSmithKline (United States) · USInstitute for Integrative and Experimental Genomics · DEJohns Hopkins University · USMontreal Heart Institute · CAPAREXEL International (United States) · USUConn Health · USUniversity of Minnesota · USUniversity of Washington · USUppsala University · SEWake Forest University · US

Funding

Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrea L Hevener · 2003 to 2026
$40.4M
Clinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2M
Genomic and Proteomic Architecture of AtherosclerosisR01HL111362 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI HERRINGTON, DAVID MCLEOD · 2012 to 2021
$17.2M
UCLA CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTEUL1RR033176 · NCRR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2011 to 2011
$15.5M
Multi-Ethnic Study of Atherosclerosis (MESA) StudyR01HL071205 · NHLBI · CEDARS-SINAI MEDICAL CENTER · PI ROTTER, JEROME I · 2003 to 2007
$10.4M
The Role of Scavenger Receptor Class B Type 1 in HumansR01HL075646 · NHLBI · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI RODRIGUEZ, ANNABELLE · 2004 to 2013
$4.5M
Lympocyte Activation Gene-3 Deficiency Linked to Proinflammation and AtherosclerosisR01HL131862 · NHLBI · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI RODRIGUEZ, ANNABELLE · 2016 to 2019
$3.0M
MESA Family StudyR01HL071250 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LIU, KIANG JOHN · 2003 to 2007
$991k
MESA Family StudyR01HL071258 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI BURKE, GREGORY L · 2003 to 2007
$918k
MESA Family StudyR01HL071259 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI POST, WENDY S · 2003 to 2007
$878k
NCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1 TR001079NCRR NIH HHS UL1 RR033176NHLBI NIH HHS HHSN268201500003CNHLBI NIH HHS HHSN268201500003INHLBI NIH HHS N01 HC095159NHLBI NIH HHS N01 HC095160NHLBI NIH HHS N01 HC095161NHLBI NIH HHS N01 HC095162NHLBI NIH HHS N01 HC095163NHLBI NIH HHS N01 HC095164NHLBI NIH HHS N01 HC095165NHLBI NIH HHS N01 HC095166NHLBI NIH HHS N01 HC095167NHLBI NIH HHS N01 HC095168NHLBI NIH HHS R01 HL071051NHLBI NIH HHS R01 HL071205NHLBI NIH HHS R01 HL071250NHLBI NIH HHS R01 HL071251NHLBI NIH HHS R01 HL071258NHLBI NIH HHS R01 HL071259NHLBI NIH HHS R01 HL075646NHLBI NIH HHS R01 HL111362NHLBI NIH HHS R01 HL131862NIDDK NIH HHS P30 DK063491
6 · The paper itself

Abstract

backgroundWe 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-PLA2 mass and activity, we hypothesized that inflammatory pathways might mediate the association of rs10846744 with atherosclerosis.

methodsWe 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-PLA2 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-PLA2 activity, cardiovascular outcomes, and interaction with the Lp-PLA2 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.

resultsSCARB1 rs10846744 was associated with coronary artery disease events in CARDIoGRAMplusC4D (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-PLA2 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-PLA2 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-PLA2 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-PLA2 activity, atherosclerosis, and CVD events, but Lp-PLA2 activity is not a mediator in the association of rs10846744 with cIMT in MESA.

Indexed as

Genetic Predisposition to DiseasePolymorphism, Single Nucleotide1-Alkyl-2-acetylglycerophosphocholine EsteraseAgedBiomarkersCardiovascular DiseasesFemaleGenome-Wide Association StudyHumansMaleMiddle AgedRisk FactorsScavenger Receptors, Class B1-Alkyl-2-acetylglycerophosphocholine EsteraseBiomarkersPLA2G7 protein, humanSCARB1 protein, humanScavenger Receptors, Class B

Identifiers

PMID30289950
PMCPMC6173398
OpenAlexW2894587712

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.