Genetic variants in human CLOCK associate with total energy intake and cytokine sleep factors in overweight subjects (GOLDN population)
Open accessAbstract
Despite the importance of total energy intake in circadian system regulation, no study has related human CLOCK gene polymorphisms and food-intake measures. The aim of this study was to analyze the associations of CLOCK single-nucleotide polymorphisms (SNPs) with food intake and to explore the specific role of the cytokine system. A total of 1100 individual participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study were included. Dietary intake was estimated with a validated questionnaire. Interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP1), tumor necrosis factor-alpha (TNF-alpha), IL-2 soluble receptor-alpha (IL-2sR-alpha) and adiponectin plasma concentrations were measured. Our results showed that four of five CLOCK SNPs selected were significantly associated with total energy intake (P<0.05). For SNP rs3749474, the energy intake and total fat, protein and carbohydrate intakes were significantly higher in minor allele carriers than in non-carriers. Frequency of the minor allele was greater in subjects with high energy intake than in those with low intake. Subjects with the minor allele were 1.33 times more likely to have high energy intake than non-carriers (95% CI 1.09-1.72, P=0.0350). All CLOCK SNPs were associated with plasma cytokine values, in particular with those that were highly correlated with energy intake: MCP1, IL-6 and adiponectin. Interestingly, minor allele carriers with high energy intake showed decreased cytokine values, which could be related with a lower anorectic effect and decreased sleep in these subjects. In conclusion, we show a novel association of genetic variation at CLOCK with total energy intake, which was particularly relevant for SNP rs3749474. Associations could be mediated through the alteration of cytokine levels that may influence energy intake and sleep pattern.
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All CLOCK SNPs were associated with plasma cytokine concentrations, particularly monocyte chemotactic protein 1, IL-6, and adiponectin.
“Moreover, all CLOCK SNPs were associated with plasma cytokine concentrations, in particular with those that were highly correlated with energy intake (i.e., monocyte chemotactic protein 1, IL-6, and adiponectin).”
From Circadian rhythms, metabolism, and chrononutrition in rodents and humans (2016) · cites this paper as [55]
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- Authors
- Garaulet, M., Lee, Y.-C., Shen, J., Parnell, L. D., Arnett, D. K., Tsai, M. Y., Lai, C.-Q., & Ordovas, J. M.
- Affiliations
- Tufts University (US)
- University of Alabama at Birmingham (US)
- University of Minnesota (US)
- Corresponding author
- Garaulet, Marta
- Venue
- European Journal of Human Genetics
- Published
- 2009-11-04
- Volume
- 18
- Issue
- 3
- Pages
- 364-369
- ISSN
- 1018-4813 (ISSN-L)
- 1476-5438
- PMC
- PMC2987209
- OpenAlex
- W2141743988
- Cited by
- 101
- References
- 46
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 6 · 2023: 6 · 2022: 7 · 2021: 8 · 2020: 8 · 2019: 2 · 2018: 5 · 2017: 5 · 2016: 6 · 2015: 8 · 2014: 8 · 2013: 5 · 2012: 7
- FWCI
- 3.59
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- European Journal of Human Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Agriculture (58-1950-9-001, 53‐K06‐5‐10)
- Fundación Séneca (02934/PI/05)
- National Institutes of Health (58-1950-9-001, DK075030)
- National Heart, Lung, and Blood Institute (U 01 HL72524, U01 HL-54776, U01HL072524, R01HL054776)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-075030, R01DK075030)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- clock genes, single nucleotide polymorphisms, total energy intake, dietary intake, cytokines, interleukin-6, MCP-1, TNF-α, adiponectin, overweight, circadian rhythm, sleep
- MeSH terms
- Energy Intake, Female, Genotype, Humans, Interleukins, Male, Sleep, Genetic Variation, Linkage Disequilibrium, Cytokines, Polymorphism, Single Nucleotide, Overweight, CLOCK Proteins
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