Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Nov 28;10(6):769-777.
doi: 10.14744/nci.2023.22120. eCollection 2023.

Association of childhood asthma with Gasdermin B (GSDMB) and Oromucoid-like 3 (ORMDL3) genes

Mehmet Almacioglu  1 , Ozlem Keskin  2 , Mehmet Yasar Ozkars  2 , Sibel Oguzkan Balci  3 , Ercan Kucukosmanoglu  2 , Sacide Pehlivan  4 , Mehmet Keskin  5
Affiliations

Association of childhood asthma with Gasdermin B (GSDMB) and Oromucoid-like 3 (ORMDL3) genes

Mehmet Almacioglu et al. North Clin Istanb. .

Abstract

Objective: Genome-length association studies have shown that Gasdermin B (GSDMB) and Orosomucoid-like 3 (ORMDL3) genes located on the long arm of chromosome 17 are associated with asthma. In this study, it was aimed to determine the possible relationship between asthma control test (ACT), exercise provocation test (ECT), and fractional nitric oxide (FENO) levels and GSDMB and ORMDL3 gene expressions.

Methods: 59 asthmatic and 38 non-asthmatic children were included in the study. We divided the patient group into two subgroups as mild persistent asthma (29 patients) and moderate persistent asthma (30 patients). ORMDL3, GSDMB gene expression levels, ECT, total IgE levels, and eosinophil counts were measured in all cases. In addition, ACT and FeNO levels were measured in children with asthma. Afterward, the relationship of ORMDL3 and GSDMB gene expression coefficient changes with ECT, ACT, and FeNO was examined.

Results: When patients with ACT ≤15 were compared with patients with ACT ≥20, ORMDL3 and GSDMB gene expressions were increased 6.74 and 11.74 times, respectively. Comparing patients with ACT ≥20 and ACT ≤15 in terms of coefficient changes (ΔCq), higher change values were observed for ΔCq ORMDL3 in patients with ACT ≤15 (p=0.015). Similarly, when patients with FENO ≤25 ppb were compared with patients with FENO >25 ppb, ORMDL3 and GSDMB gene expressions were increased by 2.93 and 3.56 times, respectively. When the coefficient changes were compared, no significant difference was found between FENO≤25 and FENO >25 patients. There was a slight negative correlation between ΔCq values and ACT score (p=0.003, r=-0.418 for ORMDL3, and p=0.016, r=-0.345 for GSDMB). In addition, we observed a statistically significant positive correlation between ORMDL3 and GSDMB gene expressions (r=0.80, p<0.001).

Conclusion: We showed that increased ORMDL3 and GSDMB gene expression levels may be associated with ACT scores, FeNO and ECT in asthma. These findings may encourage future studies with larger numbers of subjects that can use gene expression levels in various asthma phenotypes for prognostic prediction.

Keywords: Airway hyperresponsiveness; GSDMB gene expression; ORMDL3 gene expression; childhood asthma; exercise challenge test.

PubMed Disclaimer

Conflict of interest statement

No conflict of interest was declared by the authors.

Figures

FIGURE 1
FIGURE 1
Comparison of FeNOwith ACT (*Spearmancorrelation test).
FIGURE 2
FIGURE 2
Comparison of ORMDL3/GSDMB genes FC and ΔCq values according to the FeNO level (*Mann–Whitney U-test).
FIGURE 3
FIGURE 3
Comparison of ORMDL3/GSDMB genes FC and ΔCq values according to the ACT score (*Mann–Whitney U-test).
FIGURE 4
FIGURE 4
(A) Comparison of ORMDL3 genes ΔCq values according to the ACT score (*Spearman’scorrelation test). (B) Comparison of ORMDL3/GSDMB genes FC values according to ECT.
See this image and copyright information in PMC

References

    1. Moffatt MF, Kabesch M, Liang L, Dixon AL, Strachan D, Heath S, et al. Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature. 2007;448:470–3. doi: 10.1038/nature06014. - DOI - PubMed
    1. Galanter JM, Gignoux CR, Torgerson DG, Roth LA, Eng C, Oh SS, et al. Genome-wide association study and admixture mapping identify different asthma-associated loci in Latinos: the Genes-environments &Admixture in Latino Americans study. J Allergy Clin Immunol. 2014;134:295–305. doi: 10.1016/j.jaci.2013.08.055. - DOI - PMC - PubMed
    1. Stein MM, Thompson EE, Schoettler N, Helling BA, Magnaye KM, Stanhope C, et al. A decade of research on the 17q12-21 asthma locus: piecing together the puzzle. J Allergy Clin Immunol. 2018;142:749–64. - PMC - PubMed
    1. Demenais F, Margaritte-Jeannin P, Barnes KC, Cookson WOC, Altmüller J, Ang W, et al. Australian Asthma Genetics Consortium (AAGC) collaborators Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks. Nat Genet. 2018;50:42–53. doi: 10.1038/s41588-017-0014-7. - DOI - PMC - PubMed
    1. Löser S, Gregory LG, Zhang Y, Schaefer K, Walker SA, Buckley J, et al. Pulmonary ORMDL3 is critical for the induction of Alternaria-induced allergic airways disease. J Allergy Clin Immunol. 2017;139:1496–507. - PMC - PubMed