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RECERCAT Home > Universitat de Barcelona > IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer > Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) > View document

To access the full text documents, please follow this link: http://hdl.handle.net/2445/118864

dc.contributor.author Corella Piquer, Dolores
dc.contributor.author Asensio, Eva M.
dc.contributor.author Coltell, Óscar
dc.contributor.author Sorlí, José V.
dc.contributor.author Estruch Riba, Ramon
dc.contributor.author Martínez-González, Miguel Ángel, 1957-
dc.contributor.author Salas Salvadó, Jordi
dc.contributor.author Castañer, Olga
dc.contributor.author Arós, Fernando
dc.contributor.author Lapetra, José
dc.contributor.author Serra Majem, Lluís
dc.contributor.author Gómez Gracia, Enrique
dc.contributor.author Ortega Azorín, Carolina
dc.contributor.author Fiol Sala, Miguel
dc.contributor.author Díez Espino, Javier
dc.contributor.author Díaz López, Andrés
dc.contributor.author Fitó Colomer, Montserrat
dc.contributor.author Ros Rahola, Emilio
dc.contributor.author Ordovás, José M.
dc.date 2018-01-04T16:39:17Z
dc.date 2018-01-04T16:39:17Z
dc.date 2016-01-07
dc.date 2018-01-04T16:39:17Z
dc.identifier 1475-2840
dc.identifier 660181
dc.identifier 26739996
dc.identifier.uri http://hdl.handle.net/2445/118864
dc.description BACKGROUND: Circadian rhythms regulate key biological processes influencing metabolic pathways. Disregulation is associated with type 2 diabetes (T2D) and cardiovascular diseases (CVD). Circadian rhythms are generated by a transcriptional autoregulatory feedback loop involving core clock genes. CLOCK (circadian locomotor output cycles protein kaput), one of those core genes, is known to regulate glucose metabolism in rodent models. Cross-sectional studies in humans have reported associations between this locus and obesity, plasma glucose, hypertension and T2D prevalence, supporting its role in cardiovascular risk. However, no longitudinal study has investigated the association between CLOCK gene variation and T2D or CVD incidence. Moreover, although in a previous work we detected a gene-diet interaction between the CLOCK-rs4580704 (C > G) single nucleotide polymorphism (SNP) and monounsaturated (MUFA) intake on insulin resistance, no interventional study has analyzed gene-diet interactions on T2D or CVD outcomes. METHODS: We analyzed the association between the CLOCK-rs4580704 SNP and incidence of T2D and CVD longitudinally in 7098 PREDIMED trial (ISRCTN35739639) participants after a median 4.8-year follow-up. We also examined modulation by Mediterranean diet (MedDiet) intervention (high in MUFA) on these associations. RESULTS: We observed a significant association between the CLOCK-rs4580704 SNP and T2D incidence in n = 3671 non-T2D PREDIMED participants, with variant allele (G) carriers showing decreased incidence (dominant model) compared with CC homozygotes (HR: 0.69; 95 % CI 0.54-0.87; P = 0.002). This protection was more significant in the MedDiet intervention group (HR: 0.58; 95 % CI 0.43-0.78; P < 0.001) than in the control group (HR: 0.95; 95 % CI 0.63-1.44; P = 0.818). Moreover, we detected a statistically significant interaction (P = 0.018) between CLOCK-rs4580704 SNP and T2D status on stroke. Thus, only in T2D subjects was CLOCK-rs4580704 SNP associated with stroke risk, G-carriers having decreased risk (HR: 0.61; 95 % CI 0.40-0.94; P = 0.024 versus CC) in the multivariable-adjusted model. CONCLUSIONS: In agreement with our previous results showing a protective effect of the G-allele against hyperglycemia, we extended our findings by reporting a novel association with lower T2D incidence and also suggesting a dietary modulation. Moreover, we report for the first time an association between a CLOCK polymorphism and stroke in T2D subjects, suggesting that core clock genes may significantly contribute to increased CVD risk in T2D.
dc.format 12 p.
dc.format application/pdf
dc.language eng
dc.publisher BioMed Central
dc.relation Reproducció del document publicat a: https://doi.org/10.1186/s12933-015-0327-8
dc.relation Cardiovascular Diabetology, 2016, vol. 15, num. 1, p. 4
dc.relation https://doi.org/10.1186/s12933-015-0327-8
dc.rights cc-by (c) Corella Piquer, Dolores et al., 2016
dc.rights http://creativecommons.org/licenses/by/3.0/es
dc.rights info:eu-repo/semantics/openAccess
dc.subject Diabetis
dc.subject Malalties cardiovasculars
dc.subject Cuina mediterrània
dc.subject Diabetes
dc.subject Cardiovascular diseases
dc.subject Mediterranean cooking
dc.title CLOCK gene variation is associated with incidence of type-2 diabetes and cardiovascular diseases in type-2 diabetic subjects: dietary modulation in the PREDIMED randomized trial
dc.type info:eu-repo/semantics/article
dc.type info:eu-repo/semantics/publishedVersion

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CLOCK gene variation is associated with incidence of type-2 diabetes and cardiovascular diseases in type-2 diabetic subjects: dietary modulation in the PREDIMED randomized trial
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