Evidence map›Paper›PMID 23825960›Full record

ArticlePLoS genetics2013

The identification of trans-acting factors that regulate the expression of GDF5 via the osteoarthritis susceptibility SNP rs143383.

Catherine M Syddall, Louise N Reynard, David A Young, John Loughlin

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

Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 2 pooled it
3.6field-weighted citation impact, top 7% 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

37 citing papers in PubMed, 2 syntheses or guidelines pooled it, 64 citations in OpenAlex.

  1. Pooled it
  2. A comprehensive meta-analysis of association between genetic variants of GDF5 and osteoarthritis of the knee, hip and hand.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2015
    Pooled it
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  20. Association betweenExperimental and therapeutic medicine · 2018
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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

4 authors at 1 institution in 1 country.

Catherine M SyddallMusculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
Louise N Reynard
David A Young
John Loughlin
Newcastle University · GB

Funding

Medical Research Council MR/K006312/1Versus Arthritis 18746
6 · The paper itself

Abstract

rs143383 is a C to T transition SNP located in the 5'untranslated region (5'UTR) of the growth differentiation factor 5 gene GDF5. The T allele of the SNP is associated with increased risk of osteoarthritis (OA) in Europeans and in Asians. This susceptibility is mediated by the T allele producing less GDF5 transcript relative to the C allele, a phenomenon known as differential allelic expression (DAE). The aim of this study was to identify trans-acting factors that bind to rs143383 and which regulate this GDF5 DAE. Protein binding to the gene was investigated by two experimental approaches: 1) competition and supershift electrophoretic mobility shift assays (EMSAs) and 2) an oligonucleotide pull down assay followed by quantitative mass spectrometry. Binding was then confirmed in vivo by chromatin immunoprecipitation (ChIP), and the functional effects of candidate proteins investigated by RNA interference (RNAi) and over expression. Using these approaches the trans-acting factors Sp1, Sp3, P15, and DEAF-1 were identified as interacting with the GDF5 5'UTR. Knockdown and over expression of the factors demonstrated that Sp1, Sp3, and DEAF-1 are repressors of GDF5 expression. Depletion of DEAF-1 modulated the DAE of GDF5 and this differential allelic effect was confirmed following over expression, with the rs143383 T allele being repressed to a significantly greater extent than the rs143383 C allele. In combination, Sp1 and DEAF-1 had the greatest repressive activity. In conclusion, we have identified four trans-acting factors that are binding to GDF5, three of which are modulating GDF5 expression via the OA susceptibility locus rs143383.

Indexed as

5' Untranslated RegionsAllelesAllelic ImbalanceDNA-Binding ProteinsGene Expression RegulationGenetic Predisposition to DiseaseGrowth Differentiation Factor 5HumansNuclear ProteinsOsteoarthritisPolymorphism, Single NucleotideRNA InterferenceSp1 Transcription FactorSp3 Transcription FactorTranscription Factors5' Untranslated RegionsDEAF1 protein, humanDNA-Binding ProteinsGDF5 protein, humanGrowth Differentiation Factor 5Nuclear ProteinsSp1 Transcription FactorSP3 protein, humanSp3 Transcription FactorTranscription Factors

Identifiers

PMID23825960
PMCPMC3694828
OpenAlexW1990558601

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.