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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.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.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 (; 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.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 (
dc.rightsAtribución 4.0 Internacional*
dc.subjecttype-2 diabetesca_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

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    Articles de publicacions periòdiques escrits per professors del Departament de Llenguatges i Sistemes Informàtics

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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 (
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 (