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

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.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).Our findings support the view that relevant relationships between circadian clocks and the metabolic syndrome in humans exist.Circadian clocks regulate the timing of biological events including the sleep-wake cycle, energy metabolism, and secretion of hormones. The principal clock conducting the circadian system is located in the suprachiasmatic nuclei of the anterior hypothalamus. From the brain, information is sent out to regulate and reset the peripheral clocks [1]. Seasonal variations in behavior are generated by the principal clock as well [2]. Light exposures stimulate the principal clock through pathways from the retina, and the most important cues for reset of the principal circadian clock are the light-dark transitions, while the peripheral clocks are set by metabolic signals in response to feeding cycles [3]. With shortage of daylight, the metabolic cycles may take over and serve as the standard for the circadian clockwork [4]. In hibernating mammals, the metabolic futile cycle can provide the animal with those circadian signals needed for reset [5]. When there exists no light-dark transitions to reset the principal clock, reindeer living above the Arctic Circle use the metabolic cycles as the reference instead [6].The molecular circadian clock consists of multiple posi