Peripheral Blood Leukocyte Gene Expression Patterns and Metabolic Parameters in Habitually Snoring and Non-Snoring Children with Normal Polysomnographic Findings

Abstract

Children who snore but do not have gas exchange abnormalities or alterations of sleep architecture have primary snoring (PS). Since increasing evidence suggest that PS may be associated with morbidity, we hypothesized that assessing genome-wide gene expression in peripheral blood leukocytes (PBL) will identify a distinct signature in PS children. Children (aged 4-9 years) with and without habitual snoring and a normal PSG were designated as either PS or controls. Whole genome expression profiles of PBL and metabolic parameters in 30 children with PS and 30 age-, gender-, ethnicity-, and BMI-matched controls were compared. Pathway-focused gene network analysis of the PBL transcriptome was performed. Metabolic parameters were measured in an independent follow-up cohort of 98 children (64 PS and 34 controls) to evaluate the computationally derived findings. PS was not associated with a distinct transcriptional signature in PBL. Exploratory functional network analysis of enriched gene sets identified a number of putative pathways-including those mapping to insulin signaling, adipocyte differentiation, and obesity-with significant alterations in glucose metabolism and insulin sensitivity emerging in the follow-up cohort of children with PS, but no differences in lipid profiles. PS children do not exhibit global perturbations in their PBL transcriptional response, suggesting that current normative PSG criteria are overall valid. However, subtle differences in functionally coherent pathways involved in glycemic homeostasis were detected and confirmed in a larger independent pediatric cohort indicating that PS may carry increased risk for end-organ morbidity in susceptible children.