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This Article Full Text (Publish Ahead of Print[PDF]) All Versions of this Article: 90/6/1466    most recent ajcn.2009.27536v1 Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Garaulet, M. Articles by Ordovas, J. M PubMed PubMed Citation Articles by Garaulet, M. Articles by Ordovas, J. M Agricola Articles by Garaulet, M. Articles by Ordovas, J. M

CLOCK genetic variation and metabolic syndrome risk: modulation by monounsaturated fatty acids^1,2,3

¹ From the Department of Physiology, University of Murcia, Murcia, Spain (MG); the Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University School of Medicine, Boston, MA (MG, Y-CL, JS, LDP, C-QL, and JMO); the Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL (DKA); and the Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN (MYT).

² Supported by the Seneca Foundation from the Government of Murcia (project 02934/PI/05 to MG); the Government of Education, Science and Research of Murcia (project BIO/FFA 07/01-0004 to MG); The Spanish Government of Science and Innovation (projects AGL2008-01655/ALI to MG); and NIH (1R21AR055228-01A1, U01 HL72524, HL54776, and DK075030) and the US Department of Agriculture Research Service (53-K06-5-10 and 58–1950-9-001) to JMO and DKA.

³ Address correspondence to M Garaulet, Department of Physiology, Faculty of Biology, University of Murcia, Campus de Espinardo, s/n 30100, Murcia, Spain. E-mail: garaulet{at}um.es.

ABSTRACT

Background: Disruption of the circadian system may be causal for manifestations of the metabolic syndrome (MetS).

Objective: The objective was to study the associations of 5 CLOCK polymorphisms with MetS features by analyzing fatty acid (FA) composition from dietary and red blood cell (RBC) membrane sources.

Design: Participants (n = 1100) in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study were included. Dietary intake was estimated with a validated questionnaire. Anthropometric and biochemical measurements and genotypes were determined. Postprandial lipids and the FA composition of RBC membranes were analyzed.

Results: CLOCK single nucleotide polymorphisms were significantly associated with obesity and individual components of MetS. For single nucleotide polymorphism rs4580704, minor allele carriers had a 46% lower risk of hypertension than did noncarriers. The monounsaturated fatty acid (MUFA) content of RBC membranes, particularly oleic acid, changed according to CLOCK genetic variants (P < 0.05). We identified significant gene-diet interactions associated with MetS at the CLOCK locus. By dichotomizing MUFA intake, we found different effects across rs4580704 genotypes for glucose (P = 0.020) and insulin resistance (P = 0.026). The protective effect of the minor allele on insulin sensitivity was only present when MUFA intake was >13.2% of energy. We also found different effects across CLOCK 3111TC genotypes for saturated fatty acid intake (% of energy) (P = 0.017). The deleterious effect of gene variants on waist circumference was only found with high saturated fatty acid intakes (>11.8%).

Conclusions: CLOCK polymorphisms interact with FAs to modulate MetS traits. The dietary source and membrane content of MUFAs are implicated in the relations between alterations in the circadian system and MetS.

Received for publication January 23, 2009. Accepted for publication September 20, 2009.