Abstract
Increased adenosine levels throughout the day promote sleepiness. A single nucleotide polymorphism (SNP) in the adenosine deaminase ADA gene (rs73598374) has been shown to affect sleep regulation. The extent to which lower ADA enzymatic activity is associated with the homeostatic sleep factor, melatonin, is uncertain. To test this possibility, we assessed the relationship between the ADA polymorphism and evening melatonin levels, as well as self-reported sleep behavior. Given the close relationship between mood and sleep behavior, we further tested the impact of ADA genotype on self-reported mood. We show that relative to the GG homozygotes, the A allele carriers (higher adenosine levels) had significantly higher evening melatonin levels as well as significantly better sleep quality. We further show the correlations between sleep and mood measures were altered by ADA genotype, with a stronger relationship observed in the GG (lower adenosine) group. Combined, these findings advance our understanding of the biochemistry of melatonin production by showing that there is a relationship between ADA genotype and melatonin levels. The differential relationships between sleep and psychological health between the genotype groups may reveal novel insights about the development of genotype-specific progression of various psychological disorders such as chronic anxiety and stress.
Highlights
The purine nucleoside adenosine has been clearly established as a somnogenic product of adenosine triphosphate (ATP) degradation: extracellular adenosine levels in the basal forebrain increase during the day or with prolonged wakefulness and decline with subsequent sleep [1,2,3]
Given the critical role that adenosine and melatonin play in sleep and wakefulness, and the demonstrated role of Adenosine deaminase (ADA) genotype in sleep depth, we examined selfreported measures of sleep health
To further test the hypothesis that ADA genotype may alter psychological health, we examined the correlations between melatonin and the psychological health variables in each genotype separately
Summary
The purine nucleoside adenosine has been clearly established as a somnogenic product of adenosine triphosphate (ATP) degradation: extracellular adenosine levels in the basal forebrain increase during the day or with prolonged wakefulness and decline with subsequent sleep [1,2,3]. Adenosine deaminase (ADA) is responsible for metabolizing adenosine to inosine and functional changes in the ADA gene can affect ADA enzyme activity. A functional G to A single nucleotide polymorphism (SNP) at nucleotide 22 of exon 1 in the ADA gene changes Asp to Asn, which modulates the activity of the ADA enzyme (rs73598374). Carriers of the ADA A allele have lower enzymatic activity, and higher levels of circulating and intracellular adenosine levels relative to individuals who are homozygous for the G allele [4,5,6]. Converging lines of evidence demonstrate a role for this ADA polymorphism in sleep behavior wherein carriers of the AG polymorphism (decreased ADA enzymatic activity) show increased amounts of slow wave sleep and a reduced number of nocturnal awakenings [7,8,9]. The mechanisms through which ADA activity can influence sleep are currently uncertain
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