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polymorphism has also been shown to be one of the alleles associated with
self-reported adaptation levels to shift-work schedules and sleep phase in
In vitro
studies
demonstrate that these promoter polymorphisms may modify the transcrip-
tion of
PER3
.
PER3 may exert effects on sleep homeostasis. Individuals homozygous
for the 5-repeat allele exhibit increase in markers of sleep homeostasis,
including slow-wave sleep, EEG slow-wave activity (0.75-4.5 Hz) in
non-REM sleep, as well as theta and alpha activity (8-12 Hz) during
as a result of sleep deprivation is significantly larger in subjects homozygous
for the long allele. Individuals of this genotype also performworse on tests of
executive function at early morning during sleep deprivation relative to
netic resonance imaging indicates that both genotypes recruit brain regions
typically involved in working memory, but individuals homozygous for the
short allele recruit supplemental anterior frontal, temporal, and subcortical
frontal, temporal, parietal, and occipital areas were observed in homozygotes
for the long allele. Accompanying increased slow-wave sleep in subjects
homozygous for the long allele is an elevated sympathetic predominance
and a reduction of parasympathetic predominance in the autonomic nervous
Arg, are associated with reduced daytime sleepiness, and also sleepiness in
the 4-repeat allele correlates with insomnia in alcohol-dependent patients.
99
Consistent with the idea of a role for PER3 in modulating sleep homeostasis
in human, mice deficient for
Per3
exhibit altered patterns of sleep both under
baseline condition and after sleep deprivation.
100
A role for PER3 has been implicated in metabolic processes.
PER3
639
Val is associated with T2D, while the much studied
PER3
length polymor-
phism modifies the effects of the timing and duration of sleep on BMI.
98,101
This is supported by
in vitro
study that demonstrates PER3 functions to
inhibit adipogenesis, and
Per3
knockout mice display increased adipose tis-
sue and decreased muscle tissue relative to wild type.
102
An intronic SNP in
PER3
is significantly associated with susceptibility to
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