The CLOCK 3111T/C single nucleotide polymorphism and daytime fluctuations of gastric motility in healthy young women: A preliminary study.

The 3111T/C single nucleotide polymorphism (SNP) of Circadian Locomotor Output Cycles Kaput (CLOCK) gene reportedly affects gastric motility before breakfast. It is of interest to know whether this SNP can affect the motility during the daytime. We investigated the association between the CLOCK 3111T/C SNP and several gastric motility parameters during the time period from 8:00 to 20:00 in 34 young women with scheduled meals. There were similar daytime fluctuations in gastric motility before and after the meals between the major (T/T) and minor (T/C) allele carriers. The CLOCK SNP may affect daytime gastric motility less than food stimulation.

Circadian rhythm genes CLOCK and PER3 polymorphisms and morning gastric motility in humans.

BACKGROUND: Clock 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. METHODS: Lifestyle 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. RESULTS: Subjects 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 (PER34/5 or PER35/5 genotypes: n = 65) also showed a significantly lower DF (2.55 cpm) than those with the shorter PER34/4 genotype (n = 108, 2.83 cpm, P < 0.05). Furthermore, subjects with both the T/C or C/C and PER34/5 or PER35/5 genotypes showed a significantly lower DF (2.43 cpm, P < 0.05) than subjects with other combinations of the alleles (T/T and PER34/4 genotype, T/C or C/C and PER34/4 genotypes, and T/T and PER34/5 or PER35/5 genotypes). CONCLUSIONS: 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 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.

The CLOCK 3111T/C SNP is associated with morning gastric motility in healthy young women.

Circadian locomotor output cycles kaput (CLOCK) molecule plays major roles in circadian rhythmicity and regulates daily physiological processes including digestive activity. Therefore, we hypothesized that the CLOCK 3111T/C single nucleotide polymorphism (SNP) might have adverse effects on the regulation of gastric motility. Based on the hypothesis, we investigated whether this SNP was associated with morning gastric motility. Ninety-five female university students (19.6±0.2 years) completed life-style questionnaires. Gastric motility, evaluated by electrogastrography (EGG), blood pressure (BP), and heart rate variability (HRV) were measured at 8:30 a.m. after an overnight fast. To determine the gastric motility, the spectral powers and dominant frequency (DF, a peak of the spectrum) of the EGG were calculated. No significant differences were found in breakfast frequency, energy intake, or HRV between CLOCK 3111T/C minor C allele (T/C or C/C) and T/T subjects. However, C allele carriers showed significantly lower DF than T/T subjects, suggesting slower gastric motility. Moreover, C allele carriers had a lower heart rate (HR) and tended to have lower diastolic BP compared with T/T subjects. These results support our hypothesis that this SNP is likely correlated with morning gastric motility. Such attenuated gastric and cardiovascular function that characterized CLOCK 3111C allele carriers could be affecting biological behavior in the morning.