NPAS2 and PER2 are linked to risk factors of the metabolic syndrome

BACKGROUND: Mammalian circadian clocks control multiple physiological events. The principal circadian clock generates seasonal variations in behavior as well. Seasonality elevates the risk for metabolic syndrome, and evidence suggests that disruption of the clockwork can lead to alterations in metabolism. Our aim was to analyze whether circadian clock polymorphisms contribute to seasonal variations in behavior and to the metabolic syndrome. METHODS: We genotyped 39 single-nucleotide polymorphisms (SNP) from 19 genes which were either canonical circadian clock genes or genes related to the circadian clockwork from 517 individuals drawn from a nationwide population-based sample. Associations between these SNPs and seasonality, metabolic syndrome and its risk factors were analyzed using regression analysis. The p-values were corrected for multiple testing. RESULTS: Our findings link circadian gene variants to the risk factors of the metabolic syndrome, since Npas2 was associated with hypertension (P-value corrected for multiple testing = 0.0024) and Per2 was associated with high fasting blood glucose (P-value corrected for multiple testing = 0.049). CONCLUSION: Our findings support the view that relevant relationships between circadian clocks and the metabolic syndrome in humans exist.