Evidence map›Paper›PMID 21244711›Full record

ArticleBMC genomics2011

MMP1 bimodal expression and differential response to inflammatory mediators is linked to promoter polymorphisms.

Muna Affara, Benjamin J Dunmore, Deborah A Sanders, Nicola Johnson, Cristin G Print, D Stephen Charnock-Jones

Open access · goldAbstract read
In one paragraph

Article in BMC genomics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 2 pooled it
1.2field-weighted citation impact, top 20% 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

14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 25 citations in OpenAlex.

  1. The polymorphism MMP1 -1607 (1G>2G) is associated with a significantly increased risk of cancers from a meta-analysis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015
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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

6 authors at 3 institutions in 2 countries.

Muna AffaraDepartment of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK.
Benjamin J Dunmore
Deborah A Sanders
Nicola Johnson
Cristin G Print
D Stephen Charnock-Jones
University of Cambridge · GBRosie Hospital · GBUniversity of Auckland · NZ

Funding

Biotechnology and Biological Sciences Research Council
6 · The paper itself

Abstract

backgroundIdentifying the functional importance of the millions of single nucleotide polymorphisms (SNPs) in the human genome is a difficult challenge. Therefore, a reverse strategy, which identifies functionally important SNPs by virtue of the bimodal abundance across the human population of the SNP-related mRNAs will be useful. Those mRNA transcripts that are expressed at two distinct abundances in proportion to SNP allele frequency may warrant further study. Matrix metalloproteinase 1 (MMP1) is important in both normal development and in numerous pathologies. Although much research has been conducted to investigate the expression of MMP1 in many different cell types and conditions, the regulation of its expression is still not fully understood.

resultsIn this study, we used a novel but straightforward method based on agglomerative hierarchical clustering to identify bimodally expressed transcripts in human umbilical vein endothelial cell (HUVEC) microarray data from 15 individuals. We found that MMP1 mRNA abundance was bimodally distributed in un-treated HUVECs and showed a bimodal response to inflammatory mediator treatment. RT-PCR and MMP1 activity assays confirmed the bimodal regulation and DNA sequencing of 69 individuals identified an MMP1 gene promoter polymorphism that segregated precisely with the MMP1 bimodal expression. Chromatin immunoprecipitation (ChIP) experiments indicated that the transcription factors (TFs) ETS1, ETS2 and GATA3, bind to the MMP1 promoter in the region of this polymorphism and may contribute to the bimodal expression.

conclusionsWe describe a simple method to identify putative bimodally expressed RNAs from transcriptome data that is effective yet easy for non-statisticians to understand and use. This method identified bimodal endothelial cell expression of MMP1, which appears to be biologically significant with implications for inflammatory disease. (271 Words).

Indexed as

Cells, CulturedChromatin ImmunoprecipitationFemaleGATA3 Transcription FactorHumansImmunoblottingInflammation MediatorsInterleukin-1betaInterleukin-8Matrix Metalloproteinase 1Oligonucleotide Array Sequence AnalysisPolymorphism, Single NucleotideProtein BindingProto-Oncogene Protein c-ets-1Proto-Oncogene Protein c-ets-2Reverse Transcriptase Polymerase Chain ReactionETS1 protein, humanETS2 protein, humanGATA3 protein, humanGATA3 Transcription FactorInflammation MediatorsInterleukin-1betaInterleukin-8Matrix Metalloproteinase 1Proto-Oncogene Protein c-ets-1Proto-Oncogene Protein c-ets-2Tumor Necrosis Factor-alpha

Identifiers

PMID21244711
PMCPMC3040839
OpenAlexW2112150439

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.