Evidence map›Paper›PMID 30571184›Full record

Trial reportCirculation. Genomic and precision medicine2018

Tissue-Specific Differential Expression of Novel Genes and Long Intergenic Noncoding RNAs in Humans With Extreme Response to Evoked Endotoxemia.

Jane F Ferguson, Chenyi Xue, Yuanfeng Gao, Tian Tian, Jianting Shi, Xuan Zhang, Ying Wang, Yuhuang D Li, Zhi Wei, Mingyao Li and 2 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Circulation. Genomic and precision medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00953667 (The Genetics of Evoked Responses to Niacin and Endotoxemia), which is not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.3field-weighted citation impact, top 45% 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.

NCT00953667 nacompletednot on this map

The Genetics of Evoked Responses to Niacin and Endotoxemia: The GENE Study

TypeinterventionalSponsorUniversity of PennsylvaniaRan2007 to 2011Enrolled400ConditionsHealthy VolunteersArmsImmediate Release Niacin, Extended Release Niacin, Endotoxin
3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
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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

12 authors at 6 institutions in 2 countries.

Jane F FergusonDivision of Cardiovascular Medicine, and Vanderbilt Translational and Clinical Cardiovascular Research Center (VTRACC), Vanderbilt University Medical Center, Nashville, TN (J.F.F.).
Chenyi XueCardiology Division, Department of Medicine, Columbia University Medical Center, New York, NY (C.X., Y.G., J.S., X.Z., Y.W., Y.D.L., H.Z., M.P.R.).
Yuanfeng GaoCardiology Division, Department of Medicine, Columbia University Medical Center, New York, NY (C.X., Y.G., J.S., X.Z., Y.W., Y.D.L., H.Z., M.P.R.).
Tian TianDepartment of Computer Science, New Jersey Institute of Technology, Newark (T.T., Z.W.).
Jianting ShiCardiology Division, Department of Medicine, Columbia University Medical Center, New York, NY (C.X., Y.G., J.S., X.Z., Y.W., Y.D.L., H.Z., M.P.R.).
Xuan ZhangCardiology Division, Department of Medicine, Columbia University Medical Center, New York, NY (C.X., Y.G., J.S., X.Z., Y.W., Y.D.L., H.Z., M.P.R.).
Ying WangCardiology Division, Department of Medicine, Columbia University Medical Center, New York, NY (C.X., Y.G., J.S., X.Z., Y.W., Y.D.L., H.Z., M.P.R.).
Yuhuang D LiCardiology Division, Department of Medicine, Columbia University Medical Center, New York, NY (C.X., Y.G., J.S., X.Z., Y.W., Y.D.L., H.Z., M.P.R.).
Zhi WeiDepartment of Computer Science, New Jersey Institute of Technology, Newark (T.T., Z.W.).
Mingyao LiDepartment of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia (M.L.).
Hanrui ZhangCardiology Division, Department of Medicine, Columbia University Medical Center, New York, NY (C.X., Y.G., J.S., X.Z., Y.W., Y.D.L., H.Z., M.P.R.).
Muredach P ReillyCardiology Division, Department of Medicine, Columbia University Medical Center, New York, NY (C.X., Y.G., J.S., X.Z., Y.W., Y.D.L., H.Z., M.P.R.).
Columbia University Irving Medical Center · USNew Jersey Institute of Technology · USCapital Medical University · CNUniversity of Pennsylvania · USVanderbilt University Medical Center · USZunyi Medical University · CN

Funding

INSTITUTIONAL CLINICAL AND TRANSLATIONAL SCIENCE AWARDUL1RR024134 · NCRR · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 2006 to 2011
$70.4M
VIRAL VECTOR COREP30DK019525 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI MITCHELL A. LAZAR · 1986 to 2026
$48.3M
The Nicotinic Acid Receptor HM74A in Vascular InjuryP50HL083799 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 2006 to 2010
$15.8M
Elucidation of Tissue-Specific Transcriptomic Profiles in Cardiometabolic DiseaseR01HL113147 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI LI, MINGYAO, REILLY, MUREDACH P · 2012 to 2022
$6.8M
Translational Studies of ADAMTS7 a Novel GWAS Locus for Coronary AtherosclerosisR01HL111694 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI REILLY, MUREDACH P · 2012 to 2015
$2.4M
Mentored Patient Oriented Research in Cardiometabolic DiseaseK24HL107643 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI REILLY, MUREDACH P · 2011 to 2020
$1.4M
Statistical Methods for Transcriptome Profiling Using RNA SequencingR01GM108600 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI LI, MINGYAO · 2014 to 2017
$1.2M
Macrophage-specific function of GWAS CAD-associated LIPA alleles in atherosclerosisK99HL130574 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ZHANG, HANRUI · 2016 to 2017
$272k
American Heart Association-American Stroke Association 12POST11840017NCRR NIH HHS UL1 RR024134NHLBI NIH HHS K24 HL107643NHLBI NIH HHS K99 HL130574NHLBI NIH HHS P50 HL083799NHLBI NIH HHS R01 HL111694NHLBI NIH HHS R01 HL113147NIDDK NIH HHS P30 DK019525NIGMS NIH HHS R01 GM108600
6 · The paper itself

Abstract

backgroundCytokine responses to activation of innate immunity differ between individuals, yet the genomic and tissue-specific transcriptomic determinants of inflammatory responsiveness are not well understood. We hypothesized that tissue-specific mRNA and long intergenic noncoding RNA (lincRNA) induction differs between individuals with divergent evoked inflammatory responses.

methodsIn the GENE Study (Genetics of Evoked Response to Niacin and Endotoxemia), we performed an inpatient endotoxin challenge (1 ng/kg lipopolysaccharide [LPS]) in healthy humans. We selected individuals in the top (high responders) and bottom (low responders) extremes of inflammatory responses and applied RNA sequencing to CD14 monocytes (N=15) and adipose tissue (N=25) before and after LPS administration.

resultsAlthough only a small number of genes were differentially expressed at baseline, there were clear differences in the magnitude of the transcriptional response post-LPS between high and low responders, with a far greater number of genes differentially expressed by endotoxemia in high responders. Furthermore, tissue responses differed during inflammation, and we found a number of tissue-specific differentially expressed lincRNAs post-LPS, which we validated. Relative to nondifferentially expressed lincRNAs, differentially expressed lincRNAs were equally likely to be nonconserved as conserved between human and mouse, indicating that conservation is not a predictor of lincRNAs associated with human inflammatory pathophysiology. Differentially expressed genes also were enriched for signals with inflammatory and cardiometabolic disease in published genome-wide association studies. CTB-41I6.2 ( AC002091.1), a nonconserved human-specific lincRNA, is one of the top lincRNAs regulated by endotoxemia in monocytes, but not in adipose tissue. Knockdown experiments in THP-1 monocytes suggest that this lincRNA enhances LPS-induced interleukin 6 ( IL6) expression in monocytes, and we now refer to this as monocyte LPS-induced lincRNA regulator of IL6 ( MOLRIL6).

conclusionsWe highlight mRNAs and lincRNAs that represent novel candidates for modulation of innate immune and metabolic responses in humans. CLINICAL

trial registrationURL: https://www.clinicaltrials.gov . Unique identifier: NCT00953667.

Indexed as

EndotoxemiaRNA, Long NoncodingRNA, MessengerAdipose TissueAnimalsFemaleGene Expression RegulationGenome-Wide Association StudyHumansImmunity, InnateInflammationMaleMiceMonocytesSequence Analysis, RNARNA, Long NoncodingRNA, Messengeradipose tissueendotoxemiainflammationmonocyteresponse syndromesystemic inflammatory

Identifiers

PMID30571184
PMCPMC6309423
OpenAlexW2901790840

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Registered trials

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.