vasoactive-intestinal-peptide and Sleep-Apnea-Syndromes

Circadian rhythms are a nearly universal feature of living organisms and affect almost every biological process. Our innate preference for mornings or evenings is determined by the phase of our circadian rhythms. We conduct a genome-wide association analysis of self-reported morningness, followed by analyses of biological pathways and related phenotypes. We identify 15 significantly associated loci, including seven near established circadian genes (rs12736689 near RGS16, P=7.0 × 10(-18); rs9479402 near VIP, P=3.9 × 10(-11); rs55694368 near PER2, P=2.6 × 10(-9); rs35833281 near HCRTR2, P=3.7 × 10(-9); rs11545787 near RASD1, P=1.4 × 10(-8); rs11121022 near PER3, P=2.0 × 10(-8); rs9565309 near FBXL3, P=3.5 × 10(-8). Circadian and phototransduction pathways are enriched in our results. Morningness is associated with insomnia and other sleep phenotypes; and is associated with body mass index and depression but we did not find evidence for a causal relationship in our Mendelian randomization analysis. Our findings reinforce current understanding of circadian biology and will guide future studies.

Topics: Adult; Body Mass Index; Circadian Rhythm; Depression; F-Box Proteins; Female; Genetic Variation; Genome-Wide Association Study; Humans; Male; Mendelian Randomization Analysis; Middle Aged; Orexin Receptors; Period Circadian Proteins; Polymorphism, Single Nucleotide; ras Proteins; RGS Proteins; Sleep Apnea Syndromes; Sleep Initiation and Maintenance Disorders; Vasoactive Intestinal Peptide

The purpose of this study was to determine whether nasal inflammation is present in patients with obstructive sleep apnea (OSA). The number of polymorphonuclear leukocytes (PMNs) and the concentrations of bradykinin and vasoactive intestinal peptide (VIP) were quantified in nasal lavage fluid of eight nonsmoking patients with OSA and in six matched controls before sleep and the next morning. The total number of cells and the percentage of PMNs was significantly higher in patients with OSA in comparison to controls before and after sleep (P < .05). Likewise, bradykinin and VIP concentrations were significantly higher in patients with OSA in comparison to controls before and after sleep (P < .05). These findings indicate that nasal inflammation is present in patients with OSA. We suggest that nasal inflammation plays a role in upper airway obstruction in OSA.

Topics: Adult; Airway Obstruction; Bradykinin; Female; Humans; Leukocyte Count; Male; Middle Aged; Nasal Lavage Fluid; Neutrophils; Polysomnography; Rhinitis; Sleep Apnea Syndromes; Vasoactive Intestinal Peptide

Vasoactive intestinal polypeptide (VIP) is a neurotransmitter of the non-adrenergic and non-cholinergic system (NANC). It has been detected in many organs, including the airways, central and peripheral nervous system, the blood, and CSF. As a result of neuronal overflow, vagal stimulation leads to an elevation of VIP levels in the plasma. VIP leads to the activation of adenyl-cyclase, and thus to elevated cAMP in cells bearing VIP receptors. In 25 patients (24 males, 1 female) with a mean age of 50.3 +/- 9.9 years, and a Broca Index of 134.5 +/- 27.0%, plasma VIP was measured in the morning under conditions of fasting with the aid of an RIA assay (Incstar). Eleven patients (mean age: 49.4 +/- 10.1 years, Broca: 130 +/- 27.0%) had fewer than 100 episodes of apnea during nocturnal sleep (apnea/hypoapnea index 4.4 +/- 4.8). At 6.3 +/- 1.6 pcmoll-1, plasma VIP was markedly lower than that measured in 14 patients (mean age: 51.0 +/- 10.0 years, Broca: 138 +/- 28%) with the sleep apnea syndrome (apnea/hypopnea index 58.5 +/- 24.7 (means = 11.0 +/- 3.0 pcmoll-1, p less than 0.001). A significant correlation was found between the apnea episode occurring every night, and the VIP values (r = 0.64; y = -133 + 40 x VIP) measured in the plasma. The VIP measured in the plasma would appear to be a highly sensitive and highly specific indicator of the appearance of episodes of apnea during nocturnal sleep.

Topics: Adult; Female; Humans; Male; Middle Aged; Sleep Apnea Syndromes; Sleep Stages; Vasoactive Intestinal Peptide