| First Author | Aneas I | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 6115 |
| PubMed ID | 34675193 | Mgi Jnum | J:314741 |
| Mgi Id | MGI:6826716 | Doi | 10.1038/s41467-021-26347-z |
| Citation | Aneas I, et al. (2021) Asthma-associated genetic variants induce IL33 differential expression through an enhancer-blocking regulatory region. Nat Commun 12(1):6115 |
| abstractText | 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 an enhancer-blocking 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 the asthma-associated single nucleotide polymorphism (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 mechanism through which a regulatory SNP contributes to genetic risk of asthma. |
