In the Swedish Search study, we found significant differences in DNA methylation between asthmatics and controls in five CpG sites; after adjusting for lymphocyte and neutrophil cell counts, three remained significant: one in IKZF3 [IKAROS family zinc finger 3 (Aiolos); cg16293631] and two in the CpG island (CGI) of ORMDL3 (cg02305874 and cg16638648).
We examined whether polymorphisms in ORMDL3 and the adjacent gasdermin-like (GSDML) gene associated with asthma in the genome-wide association study are related to childhood asthma and atopy in a Mexico City population.
Ormdl3-LacZ reporter mice, gene-deficient Ormdl3<sup>-/-</sup> mice, and overexpressing Ormdl3<sup>Tg/wt</sup> mice were exposed to physiologically relevant aeroallergens, such as house dust mite (HDM) or Alternaria alternata, to induce experimental asthma.
The first GWAS was published in 2007, and described a new locus associated to asthma in chromosome 17q12-q21, involving the ORMDL3, GSDMB and ZPBP2 genes (a description of the genes named in the manuscript are listed in Table 1).
Collectively, our findings suggest that orosomucoid 1-like 3 (ORMDL3) locus on chromosome 17q21 is a risk factor for childhood-onset asthma in northeastern Han Chinese population.
In conclusion, our data indicate that ATRA facilitates ORMDL3 production probable through PKA/CREB, and this may be a starting point for more detailed mechanism researches on ATRA and asthma.
We sought to search for new variants associated with asthma and attempt to replicate the association with four loci reported previously (ORMDL3, PDE4D, DENND1B and IL1RL1).
We also suggest a potential unifying paradigm and discuss molecular mechanisms for the pathologic functions of ORMDL3 in asthma related to its evolutionarily conserved role in regulation of sphingolipid homeostasis.
We have studied the association of polymorphism rs4795405 in ORMDL3, rs324011 in STAT6 as well as rs8113232 and rs3786989 in TBXA2R with asthma risk, various asthma phenotypes and asthma-related symptoms.
Treatment with ICSs was significantly associated with the increase of median relative expression of ORMDL3 gene, from 0.88 to 1.21 (P=0.0032) in atopic asthmatics.
Asthma and autoimmune disease susceptibility has been strongly linked to genetic variants in the 17q21 haploblock that alter the expression of ORMDL3; however, the molecular mechanisms by which these variants perturb gene expression and the cell types in which this effect is most prominent are unclear.
This study aimed to investigate whether the p300-mediated histone acetylation (HAT) of ORMDL3 gene affects airway inflammation and remodeling in asthma.
The purpose of this study was to assess the association between the polymorphism rs4795405 in the known asthma candidate gene ORMDL3 and asthma with and without rhinitis.
We investigated whether increased ASM expression of orosomucoid-like 3 (ORMDL3), a gene on chromosome 17q21 highly linked to asthma, induced increased ASM proliferation and contractility in vitro and influenced airway contractility and calcium flux in ASM in precision-cut lung slices (PCLSs) from wild-type and hORMDL3<sup>Zp3-Cre</sup> mice (which express increased levels of human ORMDL3 [hORMDL3]).
A common genetic variation at a locus controlling the expression of the ORMDL3 locus increases the susceptibility to asthma and is associated with poor control of the condition in children and young adults.