Autor segons l'article: Corella, Dolores; Asensio, Eva M.; Coltell, Oscar; Sorli, Jose V.; Estruch, Ramon; Martinez-Gonzalez, Miguel Angel; Salas-Salvado, Jordi; Castaner, Olga; Aros, Fernando; Lapetra, Jose; Serra-Majem, Lluis; Gomez-Gracia, Enrique; Ortega-Azorin, Carolina; Fiol, Miquel; Diez Espino, Javier; Diaz-Lopez, Andres; Fito, Montserrat; Ros, Emilio; Ordovas, Jose M.;
Departament: Bioquímica i Biotecnologia
Autor/s de la URV: Díaz López, Andres / Salas Salvadó, Jorge
Paraules clau: Acute myocardial-infarction Blood-pressure surge Cardiovascular diseases Clock gene Diabetes Dna methylation Mammalian circadian clock Mediterranean diet Metabolic syndrome Obesity Risk-factors Sleep duration Stroke Transcription factor
Resum: 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.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.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.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.
Àrees temàtiques: Biotecnología Cardiac & cardiovascular systems Cardiology and cardiovascular medicine Ciências biológicas i Ciências biológicas ii Educação física Endocrinology & metabolism Endocrinology, diabetes and metabolism Farmacia Interdisciplinar Internal medicine Medicina i Medicina ii Saúde coletiva
Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
Adreça de correu electrònic de l'autor: jordi.salas@urv.cat andres.diaz@urv.cat
ISSN: 14752840
Identificador de l'autor: 0000-0003-2700-7459 0000-0002-7500-5629
Data d'alta del registre: 2023-03-05
Versió de l'article dipositat: info:eu-repo/semantics/publishedVersion
Enllaç font original: https://cardiab.biomedcentral.com/articles/10.1186/s12933-015-0327-8
Referència a l'article segons font original: Cardiovascular Diabetology. 15 (1): 4-
Referència de l'ítem segons les normes APA: Corella, Dolores; Asensio, Eva M.; Coltell, Oscar; Sorli, Jose V.; Estruch, Ramon; Martinez-Gonzalez, Miguel Angel; Salas-Salvado, Jordi; Castaner, Ol (2016). 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. Cardiovascular Diabetology, 15(1), 4-. DOI: 10.1186/s12933-015-0327-8
URL Document de llicència: http://repositori.urv.cat/ca/proteccio-de-dades/
DOI de l'article: 10.1186/s12933-015-0327-8
Entitat: Universitat Rovira i Virgili
Any de publicació de la revista: 2016
Tipus de publicació: Journal Publications
Repositori URV