Evidence map›Paper›PMID 25815003›Full record

ArticleFrontiers in genetics2015

Genetic variation in the functional ENG allele inherited from the non-affected parent associates with presence of pulmonary arteriovenous malformation in hereditary hemorrhagic telangiectasia 1 (HHT1) and may influence expression of PTPN14.

Tom G W Letteboer, Michael Benzinou, Christopher B Merrick, David A Quigley, Kechen Zhau, Il-Jin Kim, Minh D To, David M Jablons, Johannes K P van Amstel, Cornelius J J Westermann and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

11 citing papers in PubMed, 21 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Bone Morphogenetic Proteins in Vascular Homeostasis and Disease.Cold Spring Harbor perspectives in biology · 2018
    Review
  10. The roles of endoglin gene in cerebrovascular diseases.Neuroimmunology and neuroinflammation · 2017
    Article
  11. Observational
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

16 authors at 6 institutions in 4 countries.

Tom G W LetteboerHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco San Francisco, CA, USA ; Department of Medical Genetics, University Medical Centre Utrecht Utrecht, Netherlands.
Michael BenzinouHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco San Francisco, CA, USA.
Christopher B MerrickHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco San Francisco, CA, USA ; Department of Clinical Genetics, University of Dundee Dundee, UK.
David A QuigleyHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco San Francisco, CA, USA.
Kechen ZhauHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco San Francisco, CA, USA.
Il-Jin KimDepartment of Surgery, University of California, San Francisco San Francisco, CA, USA.
Minh D ToHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco San Francisco, CA, USA ; Department of Surgery, University of California, San Francisco San Francisco, CA, USA.
David M JablonsDepartment of Surgery, University of California, San Francisco San Francisco, CA, USA.
Johannes K P van AmstelDepartment of Medical Genetics, University Medical Centre Utrecht Utrecht, Netherlands.
Cornelius J J WestermannDepartment of Pulmonology, St. Antonius Hospital Nieuwegein, Netherlands.
Sophie GiraudDepartment of Medical Genetics, Lyon University Hospital Lyon, France.
Sophie Dupuis-GirodDepartment of Medical Genetics, Lyon University Hospital Lyon, France.
Gaetan LescaDepartment of Medical Genetics, Lyon University Hospital Lyon, France.
Jonathan H BergDepartment of Clinical Genetics, University of Dundee Dundee, UK.
Allan BalmainHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco San Francisco, CA, USA ; Department of Biochemistry and Biophysics, University of California, San Francisco San Francisco, CA, USA ; Institute of Human Genetics, University of California, San Francisco San Francisco, CA, USA.
Rosemary J AkhurstHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco San Francisco, CA, USA ; Institute of Human Genetics, University of California, San Francisco San Francisco, CA, USA ; Department of Anatomy, University of California, San Francisco San Francisco, CA, USA.
University of California, San Francisco · USUCSF Helen Diller Family Comprehensive Cancer Center · USHospices Civils de Lyon · FRSt. Antonius Ziekenhuis · NLUniversity Medical Center Utrecht · NLUniversity of Dundee · GB

Funding

Functional analysis of Tgfbm3 locus in vascular development and diseaseR01HL078564 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AKHURST, ROSEMARY J · 2006 to 2010
$2.8M
Circulating cells as tools to study vascular pathobiology of HHTR01HL122869 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AKHURST, ROSEMARY J · 2015 to 2018
$2.0M
Circulating cells as tools to study vascular pathobiology of HHTR56HL122869 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AKHURST, ROSEMARY J · 2014 to 2014
$511k
NHLBI NIH HHS R01 HL078564NHLBI NIH HHS R01 HL122869NHLBI NIH HHS R56 HL122869
6 · The paper itself

Abstract

HHT shows clinical variability within and between families. Organ site and prevalence of arteriovenous malformations (AVMs) depend on the HHT causative gene and on environmental and genetic modifiers. We tested whether variation in the functional ENG allele, inherited from the unaffected parent, alters risk for pulmonary AVM in HHT1 mutation carriers who are ENG haploinsufficient. Genetic association was found between rs10987746 of the wild type ENG allele and presence of pulmonary AVM [relative risk = 1.3 (1.0018-1.7424)]. The rs10987746-C at-risk allele associated with lower expression of ENG RNA in a panel of human lymphoblastoid cell lines (P = 0.004). Moreover, in angiogenically active human lung adenocarcinoma tissue, but not in uninvolved quiescent lung, rs10987746-C was correlated with expression of PTPN14 (P = 0.004), another modifier of HHT. Quantitative TAQMAN expression analysis in a panel of normal lung tissues from 69 genetically heterogeneous inter-specific backcross mice, demonstrated strong correlation between expression levels of Eng, Acvrl1, and Ptpn14 (r2 = 0.75-0.9, P < 1 × 10(-12)), further suggesting a direct or indirect interaction between these three genes in lung in vivo. Our data indicate that genetic variation within the single functional ENG gene influences quantitative and/or qualitative differences in ENG expression that contribute to risk of pulmonary AVM in HHT1, and provide correlative support for PTPN14 involvement in endoglin/ALK1 lung biology in vivo. PTPN14 has been shown to be a negative regulator of Yap/Taz signaling, which is implicated in mechanotransduction, providing a possible molecular link between endoglin/ALK1 signaling and mechanical stress. EMILIN2, which showed suggestive genetic association with pulmonary AVM, is also reported to interact with Taz in angiogenesis. Elucidation of the molecular mechanisms regulating these interactions in endothelial cells may ultimately provide more rational choices for HHT therapy.

Indexed as

ACVRL1arteriovenous malformationsEMILIN2endoglinlungPTPN14

Identifiers

PMID25815003
PMCPMC4357294
OpenAlexW2002155807

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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.