The relationship between sleep and salivary and serum inflammatory biomarkers in adolescents.

Objectives: Poor sleep behavior can trigger an inflammatory response and contribute to the development of inflammatory diseases. Cytokines can act as indicators of inflammation and may precede the onset of inflammatory diseases. This study aimed to determine the association between sleep timing parameters (bedtime, sleep duration, sleep debt, and social jetlag) and the levels of nine serum and salivary inflammatory and metabolic biomarkers. Methods: Data were collected from 352 adolescents aged 16-19 years enrolled in Kuwait's public high schools. The levels of C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), adiponectin, leptin, and insulin were measured from saliva and serum samples. We conducted mixed-effect multiple linear regression modeling to account for the school variable as a random effect to assess the relationship between the sleep variables and salivary and serum biomarkers. Mediation analysis was conducted to check if BMI was a mediator between bedtime and the biomarkers. Results: There was a statistically significant elevation in serum IL-6 level associated with later bedtime (0.05 pg./mL, p = 0.01). Adolescents with severe sleep debt of ≥2 h had an increase in salivary IL-6 biomarker levels (0.38 pg./mL, p = 0.01) compared to those who had sleep debt of <1 h. Adolescents with sleep debt of ≥2 h had significantly higher levels of serum CRP (0.61 µg/mL, p = 0.02) than those without sleep debt. Additionally, we found that the inflammatory biomarkers (CRP, IL-6, IL-8, IL-10, VEGF, and MCP-1) and metabolic biomarkers (adiponectin, leptin, and insulin) had more statistically significant associations with the bedtime variables than with sleep duration variables. CRP, IL-6, and IL-8 were associated with sleep debt, and IL-6, VEGF, adiponectin, and leptin levels were associated with social jetlag. BMIz was a full mediator in the relationship between late bedtime and increased serum levels of CRP, IL-6, and insulin. Conclusion: Adolescents who go to bed at or later than midnight had dysregulated levels of salivary and serum inflammatory biomarkers, suggesting that disrupted circadian rhythm can trigger higher levels of systemic inflammation and potentially exacerbate chronic inflammation and the risk of metabolic diseases.

The TCN2 variant of rs9606756 [Ile23Val] acts as risk loci for obesity-related traits and mediates by interacting with Apo-A1.

OBJECTIVE: Despite alarming obesity levels in the Arabian Peninsula, its population lacks convincingly identified genetic determinants of obesity. A genome-wide association study was performed for obesity-related anthropometric traits in Arabs and to decipher mechanisms by which the variants mediate traits. METHODS: The Illumina HumanOmniExpress BeadChip was used to genotype 1,353 Arab individuals (largely with Class I obesity) from Kuwait. Genome-wide association tests for obesity-related anthropometric traits were performed. Top associations were tested for replication in an independent cohort (1,176 unrelated Arabs). Resultant variants were investigated for interactions with obesity-related plasma biomarkers. Pathway analysis was performed on genes harboring markers in linkage disequilibrium (LD) with identified variants. RESULTS: The rs9606756[c.67A>G,p.Ile23Val] variant from TCN2 was associated with waist circumference (WC) at nearly genome-wide significance (P = 8.92E-08). WC was inversely related with Apo-A1 or high-density lipoprotein levels; individuals with the AG genotype exhibited stronger relationship than those with the reference AA genotype. Interaction involving the AG genotype (effect allele = G) significantly contributed to an increase in anthropometric traits (particularly WC). Genes harboring single-nucleotide polymorphisms in LD with rs9606756 mapped onto an interaction network (with TP53 as central element) of established obesity/diabetes-related protein components. CONCLUSIONS: The TCN2 variant acts as a risk factor for WC in the Arab population. The variant mediates obesity-related anthropometric traits via interactions with Apo-A1/high-density lipoprotein or TP53.