Asthma-associated variants induce IL33 differential expression through a novel regulatory region


Identification: Aneas-Ivy


Description

Asthma-associated variants induce IL33 differential expression through a novel regulatory region

Ivy Aneas1, Donna C. Decker2, D├ębora R. Sobreira1, Noboru J. Sakabe1, Kelly M. Blaine2, Kevin M. Magnaye1, Selene M. Clay1, Carole Ober1, Anne I. Sperling2,3, Marcelo A. Nobrega1.
1- Department of Human Genetics, University of Chicago, Chicago, IL; 2- Department of Medicine, Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, IL, 3- Committee on Immunology, University of Chicago, Chicago IL
Genome-wide association studies (GWAS) have implicated the IL33 locus in asthma, but the underlying mechanisms remain unclear. Here, we identify a 5 kb region within the GWAS-defined segment that acts as a strong regulatory element in vivo and in vitro. Chromatin conformation capture showed that this 5 kb region loops to the IL33 promoter, potentially regulating its expression. We show that genotype at the asthma-associated SNP rs1888909, located within the 5 kb region, is associated with IL33 gene expression in human airway epithelial cells and IL-33 protein expression in human plasma, potentially through differential binding of OCT-1 (POU2F1) to the asthma-risk allele. Our data demonstrate that asthma-associated variants at the IL33 locus mediate allele-specific regulatory activity and IL33 expression, providing a novel mechanism through which a regulatory SNP contributes to genetic risk of asthma.

Author(s)

Credits

Credits: None available.

You must be logged in and own this product in order to post comments.

Print Certificate
Completed on: token-completed_on
Print Transcript
Please select the appropriate credit type:
/
test_id: 
credits: 
completed on: 
rendered in: 
* - Indicates answer is required.
token-content

token-speaker-name
token-index
token-content
token-index
token-content
token-index
token-content
token-index
token-content
token-index
token-content
token-index
token-content
/
/
token-index
token-content
token-index
token-content