title: Beneficial effect of CLOCK gene polymorphism rs1801260 in combination with low-fat diet on insulin metabolism in the patients with metabolic syndrome.
abstract: Genetic variation at the Circadian Locomotor Output Cycles Kaput (CLOCK) locus has been associated with lifestyle-related conditions such as obesity, metabolic syndrome (MetS) and cardiovascular diseases. In fact, it has been suggested that the disruption of the circadian system may play a causal role in manifestations of MetS. The aim of this research was to find out whether habitual consumption of a low-fat diet, compared with a Mediterranean diet enriched with olive oil, modulates the associations between common CLOCK single nucleotide polymorphisms (SNPs) (rs1801260, rs3749474 and rs4580704) and lipid and glucose-related traits among MetS patients. Plasma lipid and insulin concentrations, indexes related with insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI)) and CLOCK SNPs were determined in 475 MetS subjects participating in the CORDIOPREV clinical trial (NCT00924937). Gene-diet interactions were analyzed after a year of dietary intervention (Mediterranean diet (35% fat, 22% monounsaturated fatty acids (MUFA)) versus low-fat diet (28% fat, 12% MUFA)). We found significant gene-diet interactions between rs1801260 SNP and the dietary pattern for insulin concentrations (p = 0.009), HOMA-IR (p = 0.014) and QUICKI (p = 0.028). Specifically, after 12 months of low-fat intervention, subjects who were homozygous for the major allele (TT) displayed lower plasma insulin concentrations (p = 0.032), lower insulin resistance (HOMA-IR; p = 0.027) and higher insulin sensitivity (QUICKI; p = 0.024) compared with carriers of the minor allele C (TC + CC). In contrast, in the Mediterranean intervention group a different trend was observed although no significant differences were found between CLOCK genotypes after 12 months of treatment. Our data support the notion that a chronic consumption of a healthy diet may play a contributing role in triggering glucose metabolism by interacting with the rs1801260 SNP at CLOCK gene locus in MetS patients. Due to the complex nature of gene-environment interactions, dietary adjustment in subjects with the MetS may require a personalized approach.
authors: Lipids and Atherosclerosis Unit, IMIBIC/Hospital Universitario Reina Sofía/Universidad de Córdoba , Cordoba , Spain .
authors: Antonio
authors: A
authors: Garcia-Rios
authors: Francisco Jesus
authors: FJ
authors: Gomez-Delgado
authors: Marta
authors: M
authors: Garaulet
authors: Juan Francisco
authors: JF
authors: Alcala-Diaz
authors: Francisco Javier
authors: FJ
authors: Delgado-Lista
authors: Carmen
authors: C
authors: Marin
authors: Oriol Alberto
authors: OA
authors: Rangel-Zuñiga
authors: Fernando
authors: F
authors: Rodriguez-Cantalejo
authors: Purificacion
authors: P
authors: Gomez-Luna
authors: Jose Maria
authors: JM
authors: Ordovas
authors: Francisco
authors: F
authors: Perez-Jimenez
authors: Jose
authors: J
authors: Lopez-Miranda
authors: Pablo
authors: P
authors: Perez-Martinez
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D056926:CLOCK Proteins / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics* / Q000502:physiology; D018752:Diet, Fat-Restricted / Q000009:adverse effects; D005260:Female; D059647:Gene-Environment Interaction; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009765:Obesity; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin; D056926:CLOCK Proteins; C538943:CLOCK protein, human