Genetic variants in human CLOCK associate with total energy intake and cytokine sleep factors in overweight subjects (GOLDN population)

• Published in: European journal of human genetics : EJHG Vol. 18; no. 3; pp. 364 - 369
• Main Authors: Garaulet, Marta, Lee, Yu-Chi, Shen, Jian, Parnell, Laurence D, Arnett, Donna K, Tsai, Michael Y, Lai, Chao-Qiang, Ordovas, Jose M
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.03.2010; Nature Publishing Group
• Subjects: Adiponectin; Alleles; Bioinformatics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Body weight; Carbohydrates; Circadian rhythm; Circadian rhythms; CLOCK protein; CLOCK Proteins - genetics; Cytogenetics; Cytokines; Cytokines - genetics; Dietary intake; Drugs; Energy; Energy intake; Energy Intake - genetics; Fat protein; Female; Food; Food intake; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene polymorphism; General aspects. Genetic counseling; Genes; Genetic diversity; Genetic variance; Genetic Variation; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Genotype; Human Genetics; Humans; Insulin; Interleukin 2; Interleukin 6; Interleukins - genetics; Inventories; Kinases; Linkage Disequilibrium - genetics; Lipids; Male; Medical genetics; Medical sciences; Metabolic diseases; Metabolic syndrome; Molecular and cellular biology; Monocyte chemoattractant protein 1; Monocytes; Necrosis; Nutrition research; Obesity; Overweight - genetics; Overweight - physiopathology; Physiology; Polymorphism, Single Nucleotide - genetics; Proteins; Rodents; Single-nucleotide polymorphism; Sleep; Sleep - genetics; Sleep - physiology; Studies; Tumor necrosis factor; Tumor necrosis factor-a; Tumor necrosis factor-TNF; Tumor necrosis factor-α; United States > US; Spain; energy intake; metabolic syndrome; circadian; CLOCK; obesity; interleukin-6; Endocrinopathy; Human; Obesity; Genetic variant; Nutrition disorder; Cytokine; Metabolic diseases; Cardiovascular disease; Metabolic syndrome; Overweight; Interleukin 6; Sleep; Genetics; Population; Nutritional status
• ISSN: 1018-4813; 1476-5438; 1476-5438
• DOI: 10.1038/ejhg.2009.176

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- α (TNF- α ), IL-2 soluble receptor- α (IL-2sR- α ) 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.