Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel

Probing the role of PPARγ in the regulation of late-onset Alzheimer's disease-associated genes.

Publication ,  Journal Article
Barrera, J; Subramanian, S; Chiba-Falek, O
Published in: PLoS One
2018

Peroxisome proliferator-activated receptor-γ (PPARγ), is a transcription factor that governs pathways, such as lipid metabolism and immune response, that have been implicated in the etiology of LOAD. Previously, we established HepG2-derived cell-lines with stable knockdown of PPARγ gene, and showed an increase in mRNA levels of genes mapped in the APOE linkage disequilibrium (LD) region on chromosome 19q13.32, with the greatest effect observed for APOE-mRNA. Here, we extended the analysis using our PPARγ knockdown model system and investigated the broader effect on expression changes of genes implicated in LOAD via genome wide association studies (GWAS). We applied the nCounter gene expression assay (NanoString) using a panel of twenty-four LOAD-associated genes inferred by proximity to the top significantly associated SNPs. Two independent PPARγ knockdown cell-lines showed changes in mRNA levels of a total of seven genes compared to a control HepG2 cell-line; six of which, ABCA7, APOE, CASS4, CELF1, PTK2B, and ZCWPW1, were upregulated and one, DSG2, was downregulated upon PPARγ knockdown. Our results propose that PPARγ may act as a master regulator of the transcription of several genes involved in LOAD pathogenesis. Our study provided the premise for further analyses including a larger set of genes positioned within a wider range of linkage disequilibrium (LD) regions tagged by all LOAD significantly associated SNPs.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2018

Volume

13

Issue

5

Start / End Page

e0196943

Location

United States

Related Subject Headings

  • Signal Transduction
  • RNA, Small Interfering
  • Polymorphism, Single Nucleotide
  • PPAR gamma
  • Models, Biological
  • Linkage Disequilibrium
  • Humans
  • Hep G2 Cells
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Barrera, J., Subramanian, S., & Chiba-Falek, O. (2018). Probing the role of PPARγ in the regulation of late-onset Alzheimer's disease-associated genes. PLoS One, 13(5), e0196943. https://doi.org/10.1371/journal.pone.0196943
Barrera, Julio, Shobana Subramanian, and Ornit Chiba-Falek. “Probing the role of PPARγ in the regulation of late-onset Alzheimer's disease-associated genes.PLoS One 13, no. 5 (2018): e0196943. https://doi.org/10.1371/journal.pone.0196943.
Barrera J, Subramanian S, Chiba-Falek O. Probing the role of PPARγ in the regulation of late-onset Alzheimer's disease-associated genes. PLoS One. 2018;13(5):e0196943.
Barrera, Julio, et al. “Probing the role of PPARγ in the regulation of late-onset Alzheimer's disease-associated genes.PLoS One, vol. 13, no. 5, 2018, p. e0196943. Pubmed, doi:10.1371/journal.pone.0196943.
Barrera J, Subramanian S, Chiba-Falek O. Probing the role of PPARγ in the regulation of late-onset Alzheimer's disease-associated genes. PLoS One. 2018;13(5):e0196943.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2018

Volume

13

Issue

5

Start / End Page

e0196943

Location

United States

Related Subject Headings

  • Signal Transduction
  • RNA, Small Interfering
  • Polymorphism, Single Nucleotide
  • PPAR gamma
  • Models, Biological
  • Linkage Disequilibrium
  • Humans
  • Hep G2 Cells
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease