APOBR is downregulated in EBV+ tonsils of children with obstructive sleep-disordered breathing

Obstructive sleep-disordered breathing (oSDB) is a heterogeneous phenotype that is increasing in prevalence worldwide and has many potential co-morbidities that could severely affect quality of life. There is a need to identify biomarkers for oSDB and its co-morbidities to improve clinical management, particularly in children. 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. 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. Taken together, APOBR and DEGs in tonsillar tissues may be useful as potential biomarkers of oSDB severity and co-morbidity across the lifespan, with APOBR levels being dependent on latent EBV infection. Overall design: Differential expression analyses of (a) EBV+ vs EBV- and (b) CPAP+ vs CPAP- pediatric tonsils