Evidence map›Paper›PMID 21297076›Full record

ArticleAmerican journal of respiratory and critical care medicine2011

Haplotype association mapping of acute lung injury in mice implicates activin a receptor, type 1.

George D Leikauf, Vincent J Concel, Pengyuan Liu, Kiflai Bein, Annerose Berndt, Koustav Ganguly, An Soo Jang, Kelly A Brant, Maggie Dietsch, Hannah Pope-Varsalona and 8 more

Abstract read
In one paragraph

Article in American journal of respiratory and critical care medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

25 citing papers in PubMed, 42 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Genetic determinants of ammonia-induced acute lung injury in mice.American journal of physiology. Lung cellular and molecular physiology · 2021
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. TRPA1: Acrolein meets its target.Toxicology and applied pharmacology · 2017
    Article
  14. E3 ubiquitin ligase RFWD2 controls lung branching through protein-level regulation of ETV transcription factors.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
  15. Acute cardiopulmonary toxicity of inhaled aldehydes: role of TRPA1.Annals of the New York Academy of Sciences · 2016
    Review
  16. Article
  17. Review
  18. Functional genomic assessment of phosgene-induced acute lung injury in mice.American journal of respiratory cell and molecular biology · 2013
    Article
  19. Differential susceptibility of inbred mouse strains to chlorine-induced airway fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2013
    Article
  20. WNT1-inducible signaling pathway protein 1 contributes to ventilator-induced lung injury.American journal of respiratory cell and molecular biology · 2012
    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

18 authors at 5 institutions in 3 countries.

George D LeikaufDepartment of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15219-3130, USA. gleikauf@pitt.edu
Vincent J Concel
Pengyuan Liu
Kiflai Bein
Annerose Berndt
Koustav Ganguly
An Soo Jang
Kelly A Brant
Maggie Dietsch
Hannah Pope-Varsalona
Richard A Dopico
Y P Peter Di
Qian Li
Louis J Vuga
Mario Medvedovic
Naftali Kaminski
Ming You
Daniel R Prows
University of Occupational and Environmental Health Japan · JPEnvironmental Health · GBUniversity of Pittsburgh · USMedical College of Wisconsin · USCincinnati Children's Hospital Medical Center · US

Funding

Surrogate Biomarkers for Disease Progression in IPFP50HL084932 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI PILEWSKI, JOSEPH MARK · 2006 to 2010
$12.2M
Improving our mechanistic understanding of Electronic-cigarette, or vaping, product use-associated lung injuryU01ES015675 · NIEHS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEIKAUF, GEORGE DOUGLAS · 2006 to 2020
$8.9M
Genetic Analysis of Hyperoxia Induced Acute Lung InjuryR01HL075562 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI PROWS, DANIEL R · 2004 to 2012
$3.0M
Molecular Phenotypes within and across disease boundaries in IPF and COPDR01HL095397 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KAMINSKI, NAFTALI, SHAPIRO, STEVEN D · 2008 to 2011
$3.0M
Epithelial PLUNC as a determinant of Airway Mucosal Antimicrobial ActivityR01HL091938 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DI, YUANPU PETER · 2008 to 2012
$2.3M
Chemoprevention of lung cancer with red ginseng extractsR01AT005522 · NCCIH · WASHINGTON UNIVERSITY · PI YOU, MING · 2009 to 2012
$1.9M
MOLECULAR GENETICS OF LUNG TUMOR PROMOTION IN MICER01CA134433 · NCI · WASHINGTON UNIVERSITY · PI LIU, PENGYUAN, VIKIS, HARIS G. · 2009 to 2013
$1.5M
Chemoprevention of Lung Cancer with Anti-tumor BR01AT003203 · NCCIH · WASHINGTON UNIVERSITY · PI YOU, MING · 2007 to 2010
$1.5M
Growth Factor Protection in Acute Lung InjuryR01HL077763 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEIKAUF, GEORGE DOUGLAS · 2006 to 2009
$1.4M
Bayesian Mixture Modeling of Functional Genomics DataR01HG003749 · NHGRI · UNIVERSITY OF CINCINNATI · PI MEDVEDOVIC, MARIO · 2006 to 2009
$1.4M
Role of Metalloproteinases in Mucin Overproduction in COPDR01HL085655 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEIKAUF, GEORGE DOUGLAS · 2008 to 2011
$1.4M
Chemoprevention with mTOR & Farnesyltransferase InhibitorsR01CA113793 · NCI · WASHINGTON UNIVERSITY · PI YOU, MING · 2006 to 2010
$1.3M
NCCIH NIH HHS AT003203NCCIH NIH HHS AT005522NCI NIH HHS CA113793NCI NIH HHS CA134433NHGRI NIH HHS HG003749NHLBI NIH HHS HL075562NHLBI NIH HHS HL077763NHLBI NIH HHS HL084932NHLBI NIH HHS HL085655NHLBI NIH HHS HL091938NHLBI NIH HHS HL095397NHLBI NIH HHS R01 HL075562NIEHS NIH HHS ES015675NIEHS NIH HHS U01 ES015675NLM NIH HHS LM009662
6 · The paper itself

Abstract

rationaleBecause acute lung injury is a sporadic disease produced by heterogeneous precipitating factors, previous genetic analyses are mainly limited to candidate gene case-control studies.

objectivesTo develop a genome-wide strategy in which single nucleotide polymorphism associations are assessed for functional consequences to survival during acute lung injury in mice.

methodsTo identify genes associated with acute lung injury, 40 inbred strains were exposed to acrolein and haplotype association mapping, microarray, and DNA-protein binding were assessed. MEASUREMENTS AND MAIN

resultsThe mean survival time varied among mouse strains with polar strains differing approximately 2.5-fold. Associations were identified on chromosomes 1, 2, 4, 11, and 12. Seven genes (Acvr1, Cacnb4, Ccdc148, Galnt13, Rfwd2, Rpap2, and Tgfbr3) had single nucleotide polymorphism (SNP) associations within the gene. Because SNP associations may encompass "blocks" of associated variants, functional assessment was performed in 91 genes within ± 1 Mbp of each SNP association. Using 10% or greater allelic frequency and 10% or greater phenotype explained as threshold criteria, 16 genes were assessed by microarray and reverse real-time polymerase chain reaction. Microarray revealed several enriched pathways including transforming growth factor-β signaling. Transcripts for Acvr1, Arhgap15, Cacybp, Rfwd2, and Tgfbr3 differed between the strains with exposure and contained SNPs that could eliminate putative transcriptional factor recognition sites. Ccdc148, Fancl, and Tnn had sequence differences that could produce an amino acid substitution. Mycn and Mgat4a had a promoter SNP or 3'untranslated region SNPs, respectively. Several genes were related and encoded receptors (ACVR1, TGFBR3), transcription factors (MYCN, possibly CCDC148), and ubiquitin-proteasome (RFWD2, FANCL, CACYBP) proteins that can modulate cell signaling. An Acvr1 SNP eliminated a putative ELK1 binding site and diminished DNA-protein binding.

conclusionsAssessment of genetic associations can be strengthened using a genetic/genomic approach. This approach identified several candidate genes, including Acvr1, associated with increased susceptibility to acute lung injury in mice.

Indexed as

AcroleinActivin Receptors, Type IAcute Lung InjuryAnimalsDisease Models, AnimalFemaleHaplotypesMiceMice, Inbred APolymorphism, Single NucleotideProtein Array AnalysisAcroleinActivin Receptors, Type IAcvr1 protein, mouse

Identifiers

PMID21297076
PMCPMC3137140
OpenAlexW2023304099

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 Socratic graph.