Original articleThe CLOCK 3111T/C polymorphism is associated with hour-by-hour physical activity levels only on weekends among Japanese male and female university students
Introduction
Ensuring an appropriate level of physical activity (PA) is essential for maintaining health in young individuals, as physical inactivity is a factor that contributes to at least 35 unhealthy conditions, including cardiorespiratory and immune dysfunction [1]. Unfortunately, few young individuals perform sufficient PA to realize any benefits. Although the World Health Organization recommends that children and adolescents participate in a minimum of 60 min of moderate to vigorous PA each day [2], the PA levels among youth remain low worldwide [3]. For instance, the average daily step counts among Japanese in their 20 s (males, 7913; females, 6772) were much lower than the government targets for individuals in this age group (males, 9000; females, 8500) [4]. Effective approaches to increase PA levels in young individuals are thus still warranted.
Circadian rhythms in mammals are coordinated by an endogenous circadian clock located in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus [5]. Based on the idea that the circadian timing system has a strong influence on diurnal preference (i.e. morningness–eveningness), a series of recent investigations studied the association of morningness–eveningness with circadian clock-related genes. A single-nucleotide polymorphism (SNP) in the 3′-flanking region of the CLOCK gene (311 T/C; rs1801260) was suggested to influence sleep and activity in healthy humans. Studies have reported that the rs1801260*C allele is associated with an evening preference [6,7], although negative findings have also been reported [8], [9], [10]. Based on these inconsistent results, the influence of CLOCK 3111T/C carriers on human behavior merits further investigation.
Regarding PA, evidence concerning the link between PA and CLOCK 3111T/C is very limited. A few studies have investigated the associations between PA and CLOCK 3111T/C carriers [11,12], but these studies assessed ‘total PA levels in a day’ using questionnaires. Besides PA, a previous study further found that CLOCK 3111T/C polymorphism was associated with weekly rhythms of behavior. Garaulet et al. (2011) investigated the associations between CLOCK 3111T/C polymorphism and dietary habits among overweight/obese adults [13]. They found that breakfast hours among CLOCK 3111C carriers were later than those among T carriers, particularly during weekends [13]. Unfortunately, they only reported weekly total PA levels. Given that CLOCK genes may regulate diurnal rest-activity rhythms, the time of day in which PA is performed should be investigated.
To our knowledge, only two studies have found that CLOCK 3111T/C polymorphism influences the hour-by-hour diurnal rhythms of human PA. Bandin et al. (2013) reported that among middle-aged obese women, TC+CC carriers showed a delayed acrophase—which characterizes ‘evening-type’ subjects—in comparison to TT carriers, indicating reduced PA levels at 7:00–9:00 and 21:00–22:00, under free-living conditions [14]. Similarly, Benedetti et al. (2008) investigated diurnal PA levels among depressed patients in laboratory-based experiments [15]. They found that the hour-by-hour PA levels among CLOCK 3111C carriers were higher only in the second half of the day (from the end of lunch until lights out) and did not differ markedly in the morning [15]. These findings suggested that CLOCK 3111T/C may be associated with diurnal PA rhythms under free-living conditions.
However, one of these two studies used seven-day average PA data [14], while in the other, the sampling duration was a single day [15]. In humans, PA reflects not only biological activity-rest rhythms but also social factors and obligations, such as work or school hours. In this sense, the human activity in a given day varies, particularly between weekdays (workdays) and weekends (free days). In fact, previous studies showed that the PA levels on weekdays and weekends differed markedly among adolescents [16] and adults [17]. Because morningness and eveningness (especially eveningness) are related to the PA levels in adolescents [18] as well as adults [19], weekly PA rhythms, including sleep hours (especially on weekends), should be discussed. In the previous studies that investigated PA in a single day, morningness–eveningness, which was partly regulated by CLOCK 3111T/C polymorphisms, may have been masked by social factors. As described above, delayed breakfast hours among CLOCK 3111C carriers were more prominent on weekends than weekdays [13]. Furthermore, Randler et al. (2013) found that among adolescents (11–16 years old), social jetlag (discrepancy in a person's sleep pattern between weekdays and the weekend) was significantly associated with an increased body mass index (BMI) [20]. Based on these previous studies, comparisons between weekday and weekend behavior need to be investigated; however, such research is lacking.
Although Saturday and Sunday are both regular holidays in standard schools and offices, the diurnal rhythms on Saturdays may differ from those on Sundays. In such environments, Saturday is the first day of the weekend. Indeed, among adolescents whose bedtime changed throughout the week, the latest bedtime occurred on Friday and Saturday nights, not Sunday [21]. Traditionally, Saturday is known to be a day where one is likely to lose one's rhythms. Epidemiological studies have shown that unfavorable health events tend to occur on Saturdays (e.g. the incidence of acute myocardial infarction is increased on Saturdays) [22]. The mechanisms that underly these phenomena are unclear; however, the term ‘Saturday night palsy’ refers to focal peripheral nerve palsy as a result of nerve compression in alcohol misusers [23]. Previous studies have reported that the risks of various unhealthy behaviors, such as binge drinking [24] and hospitalization for associated traumatic brain injury [25], among young adults was more prominently increased on Saturdays than Sundays. For these reasons, behavior—including activity among young populations—on Saturdays seems to differ from that on Sundays.
Interestingly, previous studies found that not only were the objectively-measured PA levels lower on the weekend than on weekdays, the PA levels on Sunday were also significantly lower than those on Saturday in both adolescents [26] and adults [27]. Furthermore, individual differences may influence PA on Saturdays and Sundays in adults [28]. Scheers et al. (2012) found that while almost all adults become sedentary on Sunday, the difference in PA was most pronounced on Saturday, and some people (normal weight men) remained active on Saturday [28]. Therefore, morningness–eveningness and associated genetic factors (e.g. CLOCK 3111T/C polymorphisms) may be partially related to weekly PA variation, especially on weekends (Saturdays and Sundays). However, to date, no studies have focused on the associations between CLOCK 3111T/C polymorphism and the hour-by-hour PA levels for an entire week.
With this background, we hypothesized that CLOCK 3111T/C polymorphism would be associated with the weekly hour-by-hour PA rhythms on weekends, especially on Saturday. The present study therefore explored, under free-living conditions, whether or not the presence of this particular genetic CLOCK 3111T/C allele in young individuals was related to the diurnal weekly PA level. To test our hypothesis, we performed an experiment to assess the relationships between CLOCK 3111 polymorphism and diurnal PA levels using objectively-measured PA devices among young students under free-living conditions.
Section snippets
Participants and survey procedures
This cross-sectional study was based on the objectively-measured PA, which was determined using electronic accelerometers, a gene analysis, and a self-administered questionnaire survey. The study population included male and female university students (n = 215; males, n = 118; females, n = 97; age, 20.4 ± 2.9 years old) from 3 universities in Yamaguchi and Fukuoka Prefectures in Japan. Male participants were recruited from two sports-related universities, while most of the female participants
Participants (Fig. 1)
At baseline, 215 participants were enrolled in the present study; however, 70 were excluded because of missing gene samples (sampling refusal and/or insufficient sample of the oral mucosa). Thereafter, 59 were excluded due to insufficient accelerometer data (the exclusion criteria are described in Methods) or invalid questionnaire data (MEQ, wake time, bedtime or meal time values were insufficient). An additional 5 were excluded because of lack of sleep log data. The remaining 81 participants
Discussion
In the present study, we investigated the associations between CLOCK 3111T/C polymorphism and weekly hour-by-hour objectively-measured PA levels under free-living conditions. To our knowledge, this is the first publication to report the associations between CLOCK 3111T/C polymorphism and objectively measured weekly PA variations obtained from Monday to Sunday. We found that the hour-by-hour PA levels among TC+CC carriers were lower than those among TT carriers only on Saturday, after adjusting
Conclusions
In summary, our data showed that CLOCK 3111T/C polymorphism may be associated with objectively measured hour-by-hour PA only on Saturdays. However, genetic effects on wake times and bedtimes were observed throughout the week. These data suggest that to resynchronize their circadian clock system, genetically determined evening-oriented young individuals may rest on Saturdays. The CLOCK 3111T/C polymorphism may influence hour-by-hour PA levels in situations without any time restriction, such as
Funding
This study was supported by a grant-in-aid for Science Research from the Ministry of Education and Science of Japan (26750351, 16K01845) and Kao Health Foundation (2015).
Author contributions
Conceived and designed the experiments: RM HA NS. Performed the experiments: RM TH YH KO. Analyzed the data: RM HA MA NS. Wrote the paper: RM HA NS.
Declaration of Competing Interest
None.
Acknowledgments
We are grateful to all of the subjects for their cooperation.
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2023, American Journal of Lifestyle Medicine