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dc.contributor.author | Corella, Dolores | |
dc.contributor.author | Coltell, Oscar | |
dc.contributor.author | Sorli, Jose V. | |
dc.contributor.author | Estruch, Ramon | |
dc.contributor.author | Quiles, Laura | |
dc.contributor.author | Angel Martinez-Gonzalez, Miguel | |
dc.contributor.author | Salas-Salvado, Jordi | |
dc.contributor.author | Castaner, Olga | |
dc.contributor.author | Aros, Fernando | |
dc.contributor.author | Ortega-Calvo, Manuel | |
dc.contributor.author | Serra-Majem, Lluis | |
dc.contributor.author | Gomez-Gracia, Enrique | |
dc.contributor.author | Portoles, Olga | |
dc.contributor.author | Fiol, Miquel | |
dc.contributor.author | Diez Espino, Javier | |
dc.contributor.author | Basora, Josep | |
dc.contributor.author | Fito, Montserrat | |
dc.contributor.author | Ros, Emilio | |
dc.contributor.author | Ordovas, Jose M | |
dc.date.accessioned | 2017-10-20T10:33:51Z | |
dc.date.available | 2017-10-20T10:33:51Z | |
dc.date.issued | 2016 | |
dc.identifier | ISI:000389144100041 | |
dc.identifier.citation | Nutrients. 2016; 8(12):793 | |
dc.identifier.issn | 2072-6643 | |
dc.identifier.other | http://hdl.handle.net/20.500.13003/10080 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/5172 | |
dc.description.abstract | Nutrigenetic studies analyzing gene-diet interactions of the TCF7L2-rs7903146 C > T polymorphism on type-2 diabetes (T2D) have shown controversial results. A reason contributing to this may be the additional modulation by obesity. Moreover, TCF7L2-rs7903146 is one of the most influential variants in T2D-genetic risk scores (GRS). Therefore, to increase the predictive value (PV) of GRS it is necessary to first see whether the included polymorphisms have heterogeneous effects. We comprehensively investigated gene-obesity interactions between the TCF7L2-rs7903146 C > T polymorphism on T2D (prevalence and incidence) and analyzed other T2D-polymorphisms in a sub-sample. We studied 7018 PREDIMED participants at baseline and longitudinally (8.7 years maximum follow-up). Obesity significantly interacted with the TCF7L2-rs7903146 on T2D prevalence, associations being greater in non-obese subjects. Accordingly, we prospectively observed in non-T2D subjects (n = 3607) that its association with T2D incidence was stronger in non-obese (HR: 1.81; 95\% CI: 1.13-2.92, p = 0.013 for TT versus CC) than in obese subjects (HR: 1.01; 95\% CI: 0.61-1.66; p = 0.979; p-interaction = 0.048). Accordingly, TCF7L2-PV was higher in non-obese subjects. Additionally, we created obesity-specific GRS with ten T2D-polymorphisms and demonstrated for the first time their higher strata-specific PV. In conclusion, we provide strong evidence supporting the need for considering obesity when analyzing the TCF7L2 effects and propose the use of obesity-specific GRS for T2D. | |
dc.description.sponsorship | This study was funded by the Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Economia y Competitividad-Fondo Europeo de Desarrollo Regional (projects PI051839, PI070240, PI1001407, G03/140, CIBER 06/03, RD06/0045 PI07-0954, CNIC-06, PI11/02505, SAF2009-12304, AGL2010-22319-C03-03, and PRX14/00527; contract JR14/00008), by the University Jaume I (Project P1-1B2013-54) and by the Generalitat Valenciana (AP111/10, AP-042/11, BEST/2015/087, GVACOMP2011-151, ACOMP/2011/145, ACOMP/2012/190, and ACOMP/2013/159). CIBEROBN is an initiative of Institute of Health Carlos III of Spain which is supported by FEDER funds (CB06/03). This material is based upon work supported by the U.S. Department of Agriculture-Agricultural Research Service (ARS), under Agreement No. 58-1950-4-003. Dolores Corella acknowledges the collaboration of the Real Colegio Complutense at Harvard University, Cambridge. MA, USA. The PREDIMED study was registered at controlled-trials.com (http://www.controlledtrials.com/ISRCTN35739639; ethics approval by the Institutional Review Board of the Hospital Clinic at Barcelona, Spain, 16/07/2002, under the protocol number G03/140). The Institutional Review Board of each participating center approved the study protocol, and all participants provided written informed consent. The Institutional Review Board of the Valencia University (protocol number G03/140, 22/05/2003) approved the PREDIMED-Valencia study protocol, and all participants provided written informed consent. | |
dc.language.iso | eng | |
dc.publisher | Multidisciplinary Digital Publishing Institute (MDPI) | |
dc.type.hasVersion | VoR | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | TCF7L2 | |
dc.subject | Type-2 diabetes | |
dc.subject | Obesity | |
dc.subject | T2D-genetic risk scores | |
dc.subject | TCF7L2-predictive value | |
dc.subject | PREDIMED study | |
dc.subject | SUSCEPTIBILITY LOCI | |
dc.subject | MEDITERRANEAN DIET | |
dc.subject | INSULIN-RESISTANCE | |
dc.subject | COMMON VARIANTS | |
dc.subject | BODY-FAT | |
dc.subject | ASSOCIATION | |
dc.subject | POPULATION | |
dc.subject | PREVENTION | |
dc.subject | TRIAL | |
dc.subject | MASS | |
dc.title | Polymorphism of the Transcription Factor 7-Like 2 Gene (TCF7L2) Interacts with Obesity on Type-2 Diabetes in the PREDIMED Study Emphasizing the Heterogeneity of Genetic Variants in Type-2 Diabetes Risk Prediction: Time for Obesity-Specific Genetic Risk Scores | |
dc.type | research article | |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 27929407 | |
dc.format.volume | 8 | |
dc.identifier.doi | 10.3390/nu8120793 | |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.contributor.funder | Jaume I University (España) | |
dc.contributor.funder | Generalitat Valenciana (España) | |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | |
dc.contributor.funder | United States Department of Agriculture. Agricultural Research Service | |
dc.description.peerreviewed | Sí | |
dc.relation.publisherversion | https://doi.org/10.3390/nu8120793 | |
dc.identifier.journal | Nutrients | |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Imagen Cardiovascular y Estudios Poblacionales | |
dc.repisalud.institucion | CNIC | |
dc.rights.accessRights | open access | es_ES |
dc.identifier.scopus | 2-s2.0-85003946080 | |
dc.identifier.wos | 389144100041 | |
dc.identifier.pui | L613545861 |
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Este ítem aparece en la(s) siguiente(s) colección(ones)
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IdisBa - Instituto de Investigación Sanitaria Illes Balears (Baleares)
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IMIM - Hospital del Mar Research Institute-Barcelona (Cataluña)
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IDIBAPS - Instituto de Investigaciones Biomédicas August Pi i Sunyer (Cataluña)
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Grupos de investigación
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IdiSNA - Instituto de Investigación Sanitaria de Navarra (Navarra)