Evidence map›Paper›PMID 28065845›Full record

ArticleBiochimica et biophysica acta. Molecular basis of disease2017

The effects of PPARγ on the regulation of the TOMM40-APOE-C1 genes cluster.

Shobana Subramanian, William K Gottschalk, So Young Kim, Allen D Roses, Ornit Chiba-Falek

Abstract read
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In one paragraph

Article in Biochimica et biophysica acta. Molecular basis of disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 2 pooled it
1.7field-weighted citation impact, top 16% 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

22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 30 citations in OpenAlex.

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  12. Genetic and regulatory architecture of Alzheimer's disease in theAlzheimer's & dementia (Amsterdam, Netherlands) · 2020
    Article
  13. Frontiers in aging neuroscience · 2020
    Review
  14. Apolipoprotein C1: Its Pleiotropic Effects in Lipid Metabolism and Beyond.International journal of molecular sciences · 2019
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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

5 authors at 2 institutions in 1 country.

Shobana SubramanianDepartment of Neurology, Duke University Medical Center, Durham, NC 27710, USA.
William K GottschalkDepartment of Neurology, Duke University Medical Center, Durham, NC 27710, USA.
So Young KimCenter for Genomic and Computational Biology, Duke University Medical Center, Durham, NC 27710, USA.
Allen D RosesDepartment of Neurology, Duke University Medical Center, Durham, NC 27710, USA; Zinfandel Pharmaceuticals, Chapel Hill, NC, USA.
Ornit Chiba-FalekDepartment of Neurology, Duke University Medical Center, Durham, NC 27710, USA; Center for Genomic and Computational Biology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: o.chibafalek@duke.edu.
Duke Medical Center · USDuke University · US

Funding

Role of the TOMM40 poly-T variant in the pathogenesis of Alzheimer's diseaseR01AG040370 · NIA · DUKE UNIVERSITY · PI CHIBA-FALEK, ORNIT · 2013 to 2017
$2.2M
NIA NIH HHS R01 AG040370
6 · The paper itself

Abstract

Chromosome 19q13.32 is a gene rich region, and has been implicated in multiple human phenotypes in adulthood including lipids traits, Alzheimer's disease, and longevity. Peroxisome Proliferator Activated Receptor Gamma (PPARγ) is a ligand-activated nuclear transcription factor that plays a role in human complex traits that are also genetically associated with the chromosome 19q13.32 region. Here, we study the effects of PPARγ on the regional expression regulation of the genes clustered within chromosome 19q13.32, specifically TOMM40, APOE, and APOC1, applying two complementary approaches. Using the short hairpin RNA (shRNA) method in the HepG2 cell-line we knocked down PPARγ expression and measured the effect on mRNA expression. We discovered PPARγ knock down increased the levels of TOMM40-, APOE-, and APOC1-mRNAs, with the highest increase in expression observed for APOE-mRNA. To complement the PPARγ knockdown findings we also examined the effects of low doses of PPARγ agonists (nM range) on mRNA expression of these genes. Low (nM) concentrations of pioglitazone (Pio) decreased transcription of TOMM40, APOE, and APOC1 genes, with the lowest mRNA levels for each gene observed at 1.5nM. Similar to the effect of PPARγ knockdown, the strongest response to pioglitazone was also observed for APOE-mRNA, and rosiglitazone (Rosi), another PPARγ agonist, produced results that were consistent with these. In conclusion, our results further established a role for PPARγ in regional transcriptional regulation of chr19q13.32, underpinning the association between PPARγ, the chr19q13.32 genes cluster, and human complex traits and disease.

Indexed as

Gene Expression RegulationMultigene FamilyApolipoprotein C-IApolipoproteins EGene Knockdown TechniquesHep G2 CellsHumansMembrane Transport ProteinsMitochondrial Precursor Protein Import Complex ProteinsPPAR gammaRNA, MessengerAPOC1 protein, humanApolipoprotein C-IApolipoproteins EMembrane Transport ProteinsMitochondrial Precursor Protein Import Complex ProteinsPPAR gammaRNA, MessengerTOMM40 protein, humanAPOC1APOEChromosome 19q13.32PPARγTOMM40Transcription

Identifiers

PMID28065845
PMCPMC5285471
OpenAlexW2569254120

What OpenQuestion holds

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LicenceTDM
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.