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

Nowakowska, Joanna ; Olechnowicz, Anna ; Langwiński, Wojciech ; Koteluk, Oliwia ; Lemańska, Żaneta ; Jóźwiak, Kacper ; Kamiński, Kacper ; Łosiewski, Wojciech ; Stegmayr, John LU and Wagner, Darcy LU orcid , et al. (2023) In Journal of Asthma 60(3). p.458-467
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 paediatric populations.

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

MATERIALS AND 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 analysed in PBMCs... (More)

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 paediatric populations.

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

MATERIALS AND 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 analysed in PBMCs from paediatric 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 analysed SNPs (rs3744246 and rs8076131) nor in the level of promoter methylation.

CONCLUSIONS: Increased ORMDL3 expression is associated with paediatric 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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Asthma
volume
60
issue
3
pages
458 - 467
publisher
Taylor & Francis
external identifiers
  • pmid:35321632
  • scopus:85129170382
ISSN
0277-0903
DOI
10.1080/02770903.2022.2056896
language
English
LU publication?
yes
id
bc1a0222-47eb-4e73-afde-d05e86e89e2f
date added to LUP
2022-03-29 22:44:48
date last changed
2024-04-15 11:45:14
@article{bc1a0222-47eb-4e73-afde-d05e86e89e2f,
  abstract     = {{<p>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 paediatric populations.</p><p>OBJECTIVES: The purpose of this study was to analyse ORMDL3 variants and expression in childhood asthma in the Polish population.</p><p>MATERIALS AND 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 analysed in PBMCs from paediatric 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.</p><p>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 analysed SNPs (rs3744246 and rs8076131) nor in the level of promoter methylation.</p><p>CONCLUSIONS: Increased ORMDL3 expression is associated with paediatric 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.</p>}},
  author       = {{Nowakowska, Joanna and Olechnowicz, Anna and Langwiński, Wojciech and Koteluk, Oliwia and Lemańska, Żaneta and Jóźwiak, Kacper and Kamiński, Kacper and Łosiewski, Wojciech and Stegmayr, John and Wagner, Darcy and Alsafadi, Hani N and Lindstedt, Sandra and Dziuba, Maria and Bielicka, Antonina and Graczyk, Zuzanna and Szczepankiewicz, Aleksandra}},
  issn         = {{0277-0903}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{458--467}},
  publisher    = {{Taylor & Francis}},
  series       = {{Journal of Asthma}},
  title        = {{Increased expression of ORMDL3 in allergic asthma : a case control and in vitro study}},
  url          = {{http://dx.doi.org/10.1080/02770903.2022.2056896}},
  doi          = {{10.1080/02770903.2022.2056896}},
  volume       = {{60}},
  year         = {{2023}},
}