昼夜节律基因CLOCK和PER3多态性与人类早晨胃动力
Circadian rhythm genes CLOCK and PER3 polymorphisms and morning gastric motility in humans.
作者信息
Yamaguchi Mitsue, Kotani Kazuhiko, Tsuzaki Kokoro, Takagi Ayaka, Motokubota Naoko, Komai Naho, Sakane Naoki, Moritani Toshio, Nagai Narumi
机构信息
Graduate School of Human Science and Environment, University of Hyogo, Hyogo, Japan.
Department of Clinical Laboratory Medicine, Jichi Medical University, Shimotsuke-Tochigi, Japan; Division of Preventive Medicine, Clinical Research Institute for Endocrine and Metabolic Disease, National Hospital Organization, Kyoto Medical Center, Kyoto, Japan.
出版信息
PLoS One. 2015 Mar 16;10(3):e0120009. doi: 10.1371/journal.pone.0120009. eCollection 2015.
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.
背景
生物钟基因调节昼夜节律，并参与包括消化在内的各种生理过程。因此，我们研究了生物钟基因CLOCK 3111T/C单核苷酸多态性和Period3（PER3）可变数目串联重复多态性（长度为54 nt的4或5个重复序列）与早晨胃动力之间的关联。
方法
对173名女性志愿者（平均年龄19.4岁）进行生活方式问卷调查和人体测量。在禁食过夜后，于上午8:30通过胃电图（EGG）评估胃动力、测量血压和心率水平。对于胃动力，评估EGG的频谱功率（正常功率百分比）和主频（DF，功率谱峰值）。通过聚合酶链反应（PCR）-限制性片段长度多态性分析确定CLOCK和PER3基因多态性。
结果
携带CLOCK基因C等位基因（T/C或C/C基因型：n = 59）的受试者的DF（平均值为2.56次/分钟）显著低于携带T/T基因型的受试者（n = 114，2.81次/分钟，P < 0.05）。携带较长PER3等位基因（PER34/5或PER35/5基因型：n = 65）的受试者的DF（2.55次/分钟）也显著低于携带较短PER34/4基因型的受试者（n = 108，2.83次/分钟，P < 0.05）。此外，携带T/C或C/C以及PER34/5或PER35/5基因型的受试者的DF（2.43次/分钟，P < 0.05）显著低于携带其他等位基因组合的受试者（T/T和PER34/4基因型、T/C或C/C和PER34/4基因型以及T/T和PER34/5或PER35/5基因型）。
结论
这些结果表明，昼夜节律基因CLOCK和PER3的微小多态性可能与早晨胃动力不佳有关，并且可能具有联合效应。本研究结果可能为昼夜节律基因在包括肠道计时功能在内的外周昼夜节律系统中的作用提供新的观点。
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