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dc.contributor.authorCorella, Dolores
dc.contributor.authorOscar, Coltell
dc.contributor.authorSorlí, José V.
dc.contributor.authorEstruch, Ramon
dc.contributor.authorQuiles Guiñau, Laura
dc.contributor.authorMartínez González, Miguel Ángel
dc.contributor.authorSalas-Salvadó, Jordi
dc.contributor.authorCastañer, Olga
dc.contributor.authorArós, Fernando
dc.contributor.authorOrtega-Calvo, Manuel
dc.contributor.authorSerra Majem, Lluís
dc.contributor.authorGómez Gracia, Enrique
dc.contributor.authorPortolés, Olga
dc.contributor.authorFiol Ramis, Miquel
dc.contributor.authorDíez Espino, Javier
dc.contributor.authorBasora, Josep
dc.contributor.authorFitó, Montserrat
dc.contributor.authorRos, Emilio
dc.contributor.authorOrdovás Muñoz, José M.
dc.date.accessioned2017-06-28T15:02:21Z
dc.date.available2017-06-28T15:02:21Z
dc.date.issued2016
dc.identifier.citationCorella, D., Coltell, O., Sorlí, J. V., Estruch, R., Quiles, L., Martínez-González, M. Á., ... & Serra-Majem, L. (2016). 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. Nutrients, 8(12), 793ca_CA
dc.identifier.issn2072-6643
dc.identifier.urihttp://hdl.handle.net/10234/168129
dc.description.abstractNutrigenetic 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. View Full-Textca_CA
dc.description.sponsorShipThis study was funded by the Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Economía 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.ca_CA
dc.format.extent18 p.ca_CA
dc.format.mimetypeapplication/pdfca_CA
dc.language.isoengca_CA
dc.publisherMDPIca_CA
dc.relation.isPartOfNutrients, 2016, vol. 8, núm. 12ca_CA
dc.rights© 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).ca_CA
dc.rightsAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectTCF7L2ca_CA
dc.subjecttype-2 diabetesca_CA
dc.subjectObesityca_CA
dc.subjectT2D-genetic risk scoresca_CA
dc.subjectTCF7L2-predictive valueca_CA
dc.subjectPREDIMED studyca_CA
dc.titlePolymorphism 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 Scoresca_CA
dc.typeinfo:eu-repo/semantics/articleca_CA
dc.identifier.doihttp://dx.doi.org/10.3390/nu8120793
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_CA
dc.relation.publisherVersionhttp://www.mdpi.com/2072-6643/8/12/793ca_CA


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© 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
Except where otherwise noted, this item's license is described as © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).