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.
Highlights
The endogenous circadian clock regulates daily oscillations in various behavioral and physiological processes of the human body, including those associated with digestive activity [1]
CLOCK and PER3 Polymorphisms and Gastric Motility. These 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 study examined the association of the CLOCK 3111T/C single nucleotide polymorphism (SNP) and PER3 variable-number tandem-repeat (VNTR) polymorphism with morning gastric motility in humans
Summary
The endogenous circadian clock regulates daily oscillations in various behavioral and physiological processes of the human body, including those associated with digestive activity [1]. The SCN and peripheral core molecular clocks consist of interconnected positive and negative transcription and translation feedback loops that oscillate every 24 hours [1, 2, 4]. In this system, the forward loop involves a set of transcriptional enhancers that induce the transcription of a set of repressors, and the negative loop feeds back to inhibit the forward loop [3,4,5]. We investigated the association between the CLOCK 3111T/ C single nucleotide polymorphism and the Period (PER3) variable-number tandem-repeat polymorphism (either 4 or 5 repeats 54 nt in length) with morning gastric motility
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