Genetic polymorphisms of DAT1 and COMT differentially associate with actigraphy-derived sleep–wake cycles in young adults. (June 2014)

• Record Type: Journal Article
• Authors: Valomon, Amandine; Holst, Sebastian C.; Bachmann, Valérie; Viola, Antoine U.; Schmidt, Christina; Zürcher, Jurian; Berger, Wolfgang; Cajochen, Christian; Landolt, Hans-Peter
• Is Part Of: Chronobiology international. Volume 31:Number 5(2014)
• Page Start: 705
• Page End: 714
• Publication Date: 2014-06
• Subjects: Chronobiology -- Periodicals; Biological rhythms -- Periodicals; Circadian rhythms -- Periodicals; 571.77
• DOI: 10.3109/07420528.2014.896376
• Languages: English
• ISSNs: 0742-0528

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p>Accumulating evidence suggests that dopamine plays a key role in sleep–wake regulation. Cerebral dopamine levels are regulated primarily by the dopamine transporter (DAT) in the striatum and by catechol-O-methyl-transferase (COMT) in the prefrontal cortex. We hypothesized that the variable-number-tandem-repeat (VNTR) polymorphism in the 3′-untranslated region of the gene encoding DAT (<italic>DAT1, SLC6A3</italic>; rs28363170) and the Val158Met polymorphism of <italic>COMT</italic> (rs4680) differently affect actigraphy-derived rest-activity cycles and sleep estimates in healthy adults (65 men; 45 women; age range: 19–35 years). Daytime sleepiness, continuous rest-actigraphy and sleep diary data during roughly 4-weeks were analyzed. Nine-repeat (9R) allele carriers of <italic>DAT1</italic> (<italic>n</italic> = 48) more often reported elevated sleepiness (Epworth sleepiness score ≥10) than 10-repeat (10R) allele homozygotes (<italic>n</italic> = 62, <italic>p</italic> < 0.02). Moreover, male 9R allele carriers showed higher wrist activity, whereas this difference was not present in women ("<italic>DAT1 genotype</italic>" × "<italic>gender</italic>" interaction: <italic>p</italic> < 0.005). Rest-activity patterns did not differ among <italic>COMT</italic> genotypes. Nevertheless, a significant "<italic>COMT genotype</italic>" × "<italic>type of day</italic>" (workdays <italic>vs.</italic> rest days) interaction for sleep duration was observed (<italic>p</italic> = 0.04). The Val/Val (<italic>n</italic> = 36) and Met/Met (<italic>n</italic> = 24) homozygotes habitually prolonged sleep on rest days compared to workdays by more than 30 min, while Val/Met heterozygotes (<italic>n</italic> = 50) did not significantly extend their sleep (mean difference: 7 min). Moreover, whereas the proportion of women among the genotype groups did not differ, <italic>COMT</italic> genotype affected body-mass-index (BMI), such that Val/Met individuals had lower BMI than the homozygous genotypes (<italic>p</italic> < 0.04). While awaiting independent replication and confirmation, our data support an association of genetically-determined differences in cerebral dopaminergic neurotransmission with daytime sleepiness and individual rest-activity profiles, as well as other sleep-associated health characteristics such as the regulation of BMI. The differential associations of <italic>DAT1</italic> and <italic>COMT</italic> polymorphisms may reflect the distinct local expression of the encoded proteins in the brain.</p> </abstract>