Increased expression of ORMDL3 in allergic asthma: a case control and in vitro study

Abstract

Background

Asthma is the most frequent chronic disease in children. One of the most replicated genetic findings in childhood asthma is the ORMDL3 gene confirmed in several GWA studies in several pediatric populations.

Objectives

The purpose of this study was to analyze ORMDL3 variants and expression in childhood asthma in the Polish population.

Methods

In the study we included 416 subject, 223 asthmatic children and 193 healthy control subjects. The analysis of two SNPs (rs3744246 and rs8076131) was performed using genotyping with TaqMan probes. The methylation of the ORMDL3 promoter was examined with Methylation Sensitive HRM (MS-HRM), covering 9 CpG sites. The expression of ORMDL3 was analyzed in PBMCs from pediatric patients diagnosed with allergic asthma and primary human bronchial epithelial cells derived from healthy subjects treated with IL-13, IL-4, or co-treatment with both cytokines to model allergic airway inflammation.

Results

We found that ORMDL3 expression was increased in allergic asthma both in PBMCs from asthmatic patients as well as in human bronchial epithelial cells stimulated with the current cytokines. We did not observe significant differences between cases and controls either in the genotype distribution of analyzed SNPs (rs3744246 and rs8076131) nor in the level of promoter methylation.

Conclusions

Increased ORMDL3 expression is associated with pediatric allergic asthma and upregulated in the airways upon Th2-cytokines stimulation, but further functional studies are required to fully understand its role in this disease.

Keywords:

• ORMDL3
• childhood asthma
• gene expression
• genetic polymorphism
• airway epithelial cells

Declaration of interest

The authors report there are no competing interests to declare.

Additional information

Funding

The study was supported by the National Science Centre, Poland, grant no. 2019/35/B/NZ5/02906 (A.S.) and grant from the Students’ Scientific Association no. 4113.