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Clinical Studies and Practice

CLOCK 3111T/C genetic variant influences the daily rhythm of autonomic nervous function: relevance to body weight control

International Journal of Obesity volume 42, pages 190–197 (2018)Cite this article

Subjects

Abstract

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.

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Acknowledgements

We thank the research volunteers for their participation. We thank Yu-Hsin Tzeng for the help of ECG preprocessing, and Tommy To for the help with the figures. This study was supported by Spanish Ministry of Economy and Competitiveness (SAF2014-52480) (to MG), by National Science Council (NCU) of Taiwan grants 104-3115-E-008-001-, 103-2321-B-008-003-, 103-2221-E-008-006-MY3 (to MTL), and by joint foundation of CGH and NCU grants CNJRF-101CGH-NCU-A4 and VGHUST103-G1-3-3 (to MTL). KH was supported by NIH grants R00-HL102241, P01AG009975 and R01AG048108. FAJLS was supported in part by NIH grants R01 DK099512, R01 HL118601 and R01 DK102696.

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Authors and Affiliations

  1. Institute of Translational and Interdisciplinary Medicine and Department of Biomedical Sciences and Engineering, National Central University, Taoyuan, Taiwan

    M-T Lo & H-W Yang

  2. Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA

    M-T Lo, F A J L Scheer, K Hu & M Garaulet

  3. Department of Physiology, University of Murcia, Murcia, Spain

    C Bandin & M Garaulet

  4. Graduate Institute of Communication Engineering, National Taiwan University, Taipei, Taiwan

    H-W Yang

  5. Division of Sleep and Circadian Disorders, Medical Biodynamics Program, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    F A J L Scheer & K Hu

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Correspondence to K Hu or M Garaulet.

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Lo, MT., Bandin, C., Yang, HW. et al. CLOCK 3111T/C genetic variant influences the daily rhythm of autonomic nervous function: relevance to body weight control. Int J Obes 42, 190–197 (2018). https://doi.org/10.1038/ijo.2017.168

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