Circadian Rhythm Genes CLOCK and PER3 Polymorphisms and Morning Gastric Motility in Humans

Abstract

BackgroundClock genes regulate circadian rhythm and are involved in various physiological processes, including digestion. We therefore investigated the association between the CLOCK 3111T/C single nucleotide polymorphism and the Period3 (PER3) variable-number tandem-repeat polymorphism (either 4 or 5 repeats 54 nt in length) with morning gastric motility.MethodsLifestyle questionnaires and anthropometric measurements were performed with 173 female volunteers (mean age, 19.4 years). Gastric motility, evaluated by electrogastrography (EGG), blood pressure, and heart rate levels were measured at 8:30 a.m. after an overnight fast. For gastric motility, the spectral powers (% normal power) and dominant frequency (DF, peak of the power spectrum) of the EGG were evaluated. The CLOCK and PER3 polymorphisms were determined by polymerase chain reaction (PCR) restriction fragment length polymorphism analysis.ResultsSubjects with the CLOCK C allele (T/C or C/C genotypes: n = 59) showed a significantly lower DF (mean, 2.56 cpm) than those with the T/T genotype (n = 114, 2.81 cpm, P < 0.05). Subjects with the longer PER3 allele (PER3 4/5 or PER3 5/5 genotypes: n = 65) also showed a significantly lower DF (2.55 cpm) than those with the shorter PER3 4/4 genotype (n = 108, 2.83 cpm, P < 0.05). Furthermore, subjects with both the T/C or C/C and PER3 4/5 or PER3 5/5 genotypes showed a significantly lower DF (2.43 cpm, P < 0.05) than subjects with other combinations of the alleles (T/T and PER3 4/4 genotype, T/C or C/C and PER3 4/4 genotypes, and T/T and PER3 4/5 or PER3 5/5 genotypes).ConclusionsThese results suggest that minor polymorphisms of the circadian rhythm genes CLOCK and PER3 may be associated with poor morning gastric motility, and may have a combinatorial effect. The present findings may offer a new viewpoint on the role of circadian rhythm genes on the peripheral circadian systems, including the time-keeping function of the gut.

A PER3 Polymorphism Interacts with Sleep Duration to Influence Transient Mood States in Women

“…We combined the PER3(4/5) and PER3(5/5) genotypes into one group due to the ubiquitous shortage of the homozygous 5-repeat allele and to isolate the effects of the 4 repeat allele. This is consistent with previous studies that have investigated this PER3 polymorphism [ 33 34 35 36 37 38 39 ]. Our cutoff score of 6 hours or less for short sleep duration was chosen since the neurobehavioral consequences of sleep restriction begin to be observed at 6 hours of sleep (or time in bed) [ 40 41 42 43 ].…”

Evolving roles of circadian rhythms in liver homeostasis and pathology

“…As a result, it has provided some novel descriptions of previously unidentified mechanisms by which the circadian clock controls the disparate liver diseases [ 162 ]. For example, unlike PER1 and 2, PER3 is not indicated to be necessary for the circadian operation, however, it has been largely accepted that PER3 might correlate with circadian regulation [ 163 , 164 ]. The robust output of liver circadian clock is derived by the orchestration between central oscillator in SCN and liver-specific local clocks, involving autoregulatory feedback loops and other uncharacterized processes [ 165 , 166 ].…”

A PERIOD3 variable number tandem repeat polymorphism modulates melatonin treatment response in delayed sleep‐wake phase disorder

“…To avoid a small sample size, we grouped those with the PER3 5/5 and PER3 4/5 alleles, as in other studies. [45][46][47] Ideally, comparing PER3 4/4 homozygotes, PER3 4/5 heterozygotes and PER3 5/5 homozygotes independently may show larger effect sizes. Furthermore, DSWPD patients recruited for this study were required to not only meet current diagnostic criteria for DSWPD 38 but also, present with a delayed circadian phase relative to desired bedtime.…”

“…First, individuals homozygous to the PER3 5/5 allele exist with relatively low frequency in humans, 20 and in our DSWPD cohort only 8.7% were genotyped with the longer allele. To avoid a small sample size, we grouped those with the PER3 5/5 and PER3 4/5 alleles, as in other studies 45‐47 . Ideally, comparing PER3 4/4 homozygotes, PER3 4/5 heterozygotes and PER3 5/5 homozygotes independently may show larger effect sizes.…”