CLOCK 3111T/C 基因变异影响自主神经功能的日常节律：与体重控制的相关性。
CLOCK 3111T/C genetic variant influences the daily rhythm of autonomic nervous function: relevance to body weight control.
机构信息
Institute of Translational and Interdisciplinary Medicine and Department of Biomedical Sciences and Engineering, National Central University, Taoyuan, Taiwan.
Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA.
出版信息
Int J Obes (Lond). 2018 Feb;42(2):190-197. doi: 10.1038/ijo.2017.168. Epub 2017 Jul 24.
BACKGROUND/OBJECTIVES: Humans carrying the genetic risk variant C at the circadian CLOCK (Circadian Locomotor Output Cycles Kaput) 3111T/C have been shown to have more difficulties to achieve desired weight loss than TT carriers. We tested the hypothesis that the daily rhythm of autonomic nervous function differs in CLOCK 3111C carriers, leading to reduced effectiveness in weight control.
SUBJECTS/METHODS: We recruited 40 overweight/obese Caucasian women (body mass index>25), 20 carrying CLOCK 3111C (CC and TC) and 20 non-carriers with matched age and body mass index who participated in a dietary obesity treatment program of up to 30 weeks. Following the treatment, ambulatory electrocardiography was continuously monitored for up to 3.5 days when subjects underwent their normal daily activities. To assess autonomic function, heart rate variability analysis (HRV) was performed hourly to obtain mean inter-beat interval between two consecutive R waves (mean RR) and s.d. of normal-to-normal heartbeat intervals (SDNN), and two parasympathetic measures, namely, proportion of differences between adjacent NN intervals that are >50 ms (pNN50), and high-frequency (HF: 0.15-0.4 Hz) power.
RESULTS
In the TT carriers, all tested HRV indices showed significant daily rhythms (all P-values <0.0001) with lower mean RR, SDNN, pNN50, and HF during the daytime as compared with the nighttime. The amplitudes of these rhythms except for SDNN were reduced significantly in the C carriers (mean RR: ~19.7%, P=0.001; pNN50: 58.1%, P=0.001; and HF: 41.1%, P=0.001). In addition, subjects with less weight loss during the treatment program had smaller amplitudes in the rhythms of mean RR (P<0.0001), pNN50 (P=0.007) and HF (P=0.003). Furthermore, the rhythmicity-weight loss associations were much stronger in the C carriers as compared to the TT carriers (mean RR: P=0.028, pNN50: P=0.0002; HF: P=0.015).
CONCLUSIONS
The daily rhythm of parasympathetic modulation may play a role in the influence of the CLOCK variation on body weight control.
背景/目的：携带生物钟（Circadian Locomotor Output Cycles Kaput）3111T/C 基因风险变异 C 的人类较 TT 携带者更难实现理想的体重减轻。我们检验了这样一个假设，即 CLOCK 3111C 携带者的自主神经功能的日常节律不同，导致体重控制的效果降低。
研究对象/方法：我们招募了 40 名超重/肥胖的白种人（体重指数>25），其中 20 名携带 CLOCK 3111C（CC 和 TC），20 名非携带者，年龄和体重指数匹配，他们参加了长达 30 周的饮食肥胖治疗计划。治疗结束后，当受试者进行正常的日常活动时，连续监测长达 3.5 天的动态心电图。为了评估自主神经功能，每小时进行心率变异性分析（HRV），以获得两个连续 R 波之间的平均间期（平均 RR）和正常-正常心跳间期的标准差（SDNN），以及两个副交感神经指标，即相邻 NN 间期差异大于 50ms 的比例（pNN50）和高频（HF：0.15-0.4Hz）功率。
结果
在 TT 携带者中，所有测试的 HRV 指标均显示出显著的日节律（所有 P 值均<0.0001），白天的平均 RR、SDNN、pNN50 和 HF 均低于夜间。这些节律的幅度除了 SDNN 之外，在 C 携带者中明显降低（平均 RR：~19.7%，P=0.001；pNN50：58.1%，P=0.001；HF：41.1%，P=0.001）。此外，在治疗期间体重减轻较少的受试者，其平均 RR 节律（P<0.0001）、pNN50 节律（P=0.007）和 HF 节律（P=0.003）的幅度较小。此外，与 TT 携带者相比，C 携带者的节律与减重之间的关联要强得多（平均 RR：P=0.028，pNN50：P=0.0002；HF：P=0.015）。
结论
副交感神经调节的日常节律可能在生物钟变异对体重控制的影响中发挥作用。
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