Dataset Information

New Insights Relating Gasdermin B to the Onset of Childhood Asthma.

ABSTRACT: Chromosome 17q12-q21 is the most replicated genetic locus for childhood-onset asthma. Polymorphisms in this locus containing ∼10 genes interact with a variety of environmental exposures in the home and outdoors to modify asthma risk. However, the functional basis for these associations and their linkages to the environment have remained enigmatic. Within this extended region, regulation of GSDMB (gasdermin B) expression in airway epithelial cells has emerged as the primary mechanism underlying the 17q12-q21 genome-wide association study signal. Asthma-associated SNPs influence the abundance of GSDMB transcripts as well as the functional properties of GSDMB protein in airway epithelial cells. GSDMB is a member of the gasdermin family of proteins, which regulate pyroptosis and inflammatory responses to microbial infections. The aims of this review are to synthesize recent studies on the relationship of 17q12-q21 SNPs to childhood asthma and the evidence pointing to GSDMB gene expression or protein function as the underlying mechanism and to explore the potential functions of GSDMB that may influence the risk of developing asthma during childhood.

SUBMITTER: Schoettler N

PROVIDER: S-EPMC9564923 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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New Insights Relating Gasdermin B to the Onset of Childhood Asthma.

Schoettler Nathan N Dissanayake Eishika E Craven Mark W MW Yee Jeremiah S JS Eliason Joshua J Schauberger Eric M EM Lemanske Robert F RF Ober Carole C Gern James E JE

American journal of respiratory cell and molecular biology 20221001 4

Chromosome 17q12-q21 is the most replicated genetic locus for childhood-onset asthma. Polymorphisms in this locus containing ∼10 genes interact with a variety of environmental exposures in the home and outdoors to modify asthma risk. However, the functional basis for these associations and their linkages to the environment have remained enigmatic. Within this extended region, regulation of <i>GSDMB</i> (gasdermin B) expression in airway epithelial cells has emerged as the primary mechanism under ...[more]

PMID: 35580164

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Project description:ObjectiveGenome-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.Methods59 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.ResultsWhen 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).ConclusionWe 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.

Dataset Information

New Insights Relating Gasdermin B to the Onset of Childhood Asthma.

Publications

New Insights Relating Gasdermin B to the Onset of Childhood Asthma.

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