PMID- 19888304 OWN - NLM STAT- MEDLINE DCOM- 20100518 LR - 20211020 IS - 1476-5438 (Electronic) IS - 1018-4813 (Print) IS - 1018-4813 (Linking) VI - 18 IP - 3 DP - 2010 Mar TI - Genetic variants in human CLOCK associate with total energy intake and cytokine sleep factors in overweight subjects (GOLDN population). PG - 364-9 LID - 10.1038/ejhg.2009.176 [doi] AB - 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. FAU - Garaulet, Marta AU - Garaulet M AD - Department of Physiology, University of Murcia, Murcia, Spain. garaulet@um.es FAU - Lee, Yu-Chi AU - Lee YC FAU - Shen, Jian AU - Shen J FAU - Parnell, Laurence D AU - Parnell LD FAU - Arnett, Donna K AU - Arnett DK FAU - Tsai, Michael Y AU - Tsai MY FAU - Lai, Chao-Qiang AU - Lai CQ FAU - Ordovas, Jose M AU - Ordovas JM LA - eng GR - U01 HL072524/HL/NHLBI NIH HHS/United States GR - R01 HL054776/HL/NHLBI NIH HHS/United States GR - U01 HL72524/HL/NHLBI NIH HHS/United States GR - U01 HL-54776/HL/NHLBI NIH HHS/United States GR - R01 DK075030/DK/NIDDK NIH HHS/United States GR - DK075030/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20091104 PL - England TA - Eur J Hum Genet JT - European journal of human genetics : EJHG JID - 9302235 RN - 0 (Cytokines) RN - 0 (Interleukins) RN - EC 2.3.1.48 (CLOCK Proteins) SB - IM MH - CLOCK Proteins/*genetics MH - Cytokines/*genetics MH - Energy Intake/*genetics MH - Female MH - *Genetic Variation MH - Genotype MH - Humans MH - Interleukins/genetics MH - Linkage Disequilibrium/genetics MH - Male MH - Overweight/*genetics/*physiopathology MH - Polymorphism, Single Nucleotide/genetics MH - Sleep/*genetics/*physiology PMC - PMC2987209 EDAT- 2009/11/06 06:00 MHDA- 2010/05/19 06:00 PMCR- 2011/03/01 CRDT- 2009/11/06 06:00 PHST- 2009/11/06 06:00 [entrez] PHST- 2009/11/06 06:00 [pubmed] PHST- 2010/05/19 06:00 [medline] PHST- 2011/03/01 00:00 [pmc-release] AID - ejhg2009176 [pii] AID - 10.1038/ejhg.2009.176 [doi] PST - ppublish SO - Eur J Hum Genet. 2010 Mar;18(3):364-9. doi: 10.1038/ejhg.2009.176. Epub 2009 Nov 4.