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Integrative Biology

Differences in circadian rhythmicity in CLOCK 3111T/C genetic variants in moderate obese women as assessed by thermometry, actimetry and body position

International Journal of Obesity volume 37, pages 1044–1050 (2013)Cite this article

Subjects

Abstract

Introduction:

Genetics is behind our circadian machinery. CLOCK (Circadian Locomotor Output Cycles Kaput) 3111T/C single-nucleotide polymorphism (SNP) has been previously related to obesity and weight loss. However, phenotypic association and functionality of CLOCK 3111 locus is still unknown. The aim of this study was to determine, in free-living conditions, if the presence of CLOCK 3111C in overweight women could be related to (a) circadian disorders, and (b) changes in sleep quality, to improve understanding of the previously demonstrated associations with obesity and reduced weight loss of the C carriers.

Methods:

Wrist temperature, actimetry and position (TAP) and TAP variables were measured as markers of circadian functionality during 8 consecutive days. A rest–activity and food diary was also completed, whereas sleep quality was determined by domiciliary polysomnography. We recruited 85 women who were overweight with body mass index (BMI) of 28.59±4.30 kg m−2 and age 43±12 years. From this sample, we found that 43 women were carrying the minor allele (C) for CLOCK 3111T/C SNP and 42 women were TT carriers (major allele carriers). Both groups of patients were matched for number, age, obesity parameters and energy intake.

Results:

Compared with TT subjects, who showed more robust circadian rhythm profiles, patients with the C allele displayed significant circadian abnormalities: lower amplitude and greater fragmentation of the rhythm, a less stable circadian pattern and a significantly weakened circadian function, as assessed by the circadian function index (CFI). C subjects were also less active, started their activities later in the morning and were sleepier during the day, showing a delayed acrophase that characterizes ‘evening-type’ subjects.

Conclusion:

C genetic variants in CLOCK 3111T/C display a less robust circadian rhythm than TT and a delayed acrophase that characterizes ‘evening-type’ subjects. We support the notion that identifying CLOCK genotypes in patients may assist the therapist in characterization of the roots of the metabolic problem.

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Acknowledgements

This study was supported by grants from Tomás Pascual and Pilar Gómez-Cuétara Foundations, Spanish Government of Science and Innovation (BFU2011-24720), Séneca Foundation from the Government of Murcia (15123/PI/10), National Heart, Lung and Blood Institute Grant HL-54776, National Institute of Diabetes and Digestive and Kidney Diseases Grant DK075030 and by contracts 53-K06-5-10 and 58-1950-9-001 from the US Department of Agriculture Research.

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Authors and Affiliations

  1. Department of Physiology, Faculty of Biology, University of Murcia, Murcia, Spain

    C Bandín, A Martinez-Nicolas, J A Madrid & M Garaulet

  2. Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Nutrition and Genomics Laboratory, Tufts University, Boston, MA, USA

    J M Ordovás

  3. Department of Epidemiology, Centro Nacional Investigaciones Cardiovasculares (CNIC), Madrid, Spain

    J M Ordovás

  4. ’Madrid Institute for Advanced Studies in Food’ (IMDEA-FOOD), Madrid, Spain

    J M Ordovás

  5. Neumology Service of Universitary Hospital ‘Virgen de Arrixaca’, Murcia, Spain

    J A Ros Lucas

  6. Instrumentation Service Psychological, University of Murcia, Murcia, Spain

    P Castell

  7. Division of Respiratory Medicine, Sleep Unit, Universitary Hospital ‘Reina Sofia’, Murcia, Spain

    T Silvente

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Correspondence to M Garaulet.

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Bandín, C., Martinez-Nicolas, A., Ordovás, J. et al. Differences in circadian rhythmicity in CLOCK 3111T/C genetic variants in moderate obese women as assessed by thermometry, actimetry and body position. Int J Obes 37, 1044–1050 (2013). https://doi.org/10.1038/ijo.2012.180

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