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Asthma-associated genetic variants induce IL33 differential expression through a novel regulatory region
- Publication Year :
- 2020
- Publisher :
- Research Square Platform LLC, 2020.
-
Abstract
- 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.
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi...........3b2a5bc926bc1f899e6a725fdf0dea46