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APOBR Is Downregulated in EBV+ Tonsils of Children with Obstructive Sleep-Disordered Breathing
Regie Lyn P Santos-Cortez1, Helen Z Gomez1, Christina L Elling1
1Department of Otolaryngology-Head and Neck Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Insights
Researchers identified potential biomarkers for obstructive sleep-disordered breathing (oSDB) in children. Downregulation of the gene APOBR in tonsils, linked to Epstein-Barr virus (EBV) and CPAP treatment, may indicate oSDB severity.
Area of Science:
- Genomics and Molecular Biology
- Sleep Medicine
- Pediatric Research
Background:
- Obstructive sleep-disordered breathing (oSDB) is a growing global health concern with significant comorbidities impacting quality of life.
- Identifying reliable biomarkers for oSDB and its associated conditions is crucial for improving clinical management, especially in pediatric populations.
Purpose of the Study:
- To identify potential biomarkers for obstructive sleep-disordered breathing (oSDB) in pediatric tonsillar tissue.
- To investigate the association of gene expression with Epstein-Barr virus (EBV) infection and the need for continuous positive airway pressure (CPAP) treatment in children with oSDB.
Main Methods:
- Bulk mRNA-sequencing and differential gene expression analysis were performed on tonsil RNA from children with oSDB.
- Gene expression was analyzed based on the presence of Epstein-Barr virus (EBV) and the requirement for CPAP treatment.
- Quantitative PCR (qPCR) was used to validate the expression of selected differentially expressed genes (DEGs) in an independent cohort.
Main Results:
- Nineteen genes were found to be dysregulated in tonsils from EBV-positive or CPAP-requiring children with oSDB.
- The gene *APOBR* was consistently downregulated in both EBV+ and CPAP+ tonsils, with this finding replicated by qPCR.
- In adult oSDB patients, *APOBR* expression showed a positive correlation with age and potentially diastolic blood pressure.
Conclusions:
- *APOBR* and other differentially expressed genes in tonsillar tissue show promise as biomarkers for oSDB severity and related comorbidities.
- The expression levels of *APOBR* may be influenced by latent Epstein-Barr virus (EBV) infection.
- These findings suggest potential diagnostic and prognostic applications of tonsillar gene expression in oSDB across different age groups.
Abstract:
Background: Obstructive sleep-disordered breathing (oSDB) is a heterogeneous phenotype that is increasing in prevalence worldwide and has many potential comorbidities that could severely affect quality of life. There is a need to identify biomarkers for oSDB and its comorbidities to improve clinical management, particularly in children. Methods: We performed bulk mRNA-sequencing, differential expression analysis, and qPCR replication of selected differentially expressed genes (DEGs) using RNA samples extracted from tonsils of children with oSDB. Two variables were used as classifier, namely, detection of Epstein-Barr virus (EBV) in tonsils and need for continuous positive airway pressure (CPAP) treatment. Standard statistical tests were used to determine associations across clinical, EBV, and DEG variables. Results: Nineteen genes were dysregulated in tonsils that are EBV+ or from children needing CPAP. Of these genes, APOBR was downregulated in both EBV+ and CPAP+ tonsils, and this downregulation was replicated by qPCR in an independent set of pediatric samples. In the tonsils of adult patients with oSDB, APOBR was positively correlated with age, and potentially with diastolic blood pressure. Conclusions: Taken together, APOBR and DEGs in tonsillar tissues may be useful as potential biomarkers of oSDB severity and comorbidity across the lifespan, with APOBR levels being dependent on latent EBV infection.
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