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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.contributor.author | Corella, Dolores | |
dc.contributor.author | Coltell, Oscar | |
dc.contributor.author | Sorlí, José V | |
dc.contributor.author | Estruch, Ramon | |
dc.contributor.author | Quiles Guiñau, Laura | |
dc.contributor.author | Martínez González, Miguel Ángel | |
dc.contributor.author | Salas-Salvadó, Jordi | |
dc.contributor.author | Castañer, Olga | |
dc.contributor.author | Arós, Fernando | |
dc.contributor.author | Ortega-Calvo, Manuel | |
dc.contributor.author | Serra-Majem, Lluis | |
dc.contributor.author | Gómez Gracia, Enrique | |
dc.contributor.author | Portolés, Olga | |
dc.contributor.author | Fiol Ramis, Miquel | |
dc.contributor.author | Díez Espino, Javier | |
dc.contributor.author | Basora, Josep | |
dc.contributor.author | Fitó, Montserrat | |
dc.contributor.author | Ros, Emilio | |
dc.contributor.author | Ordovás Muñoz, José M. | |
dc.date.accessioned | 2017-06-28T15:02:21Z | |
dc.date.available | 2017-06-28T15:02:21Z | |
dc.date.issued | 2016 | |
dc.identifier.citation | Corella, 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), 793 | ca_CA |
dc.identifier.issn | 2072-6643 | |
dc.identifier.uri | http://hdl.handle.net/10234/168129 | |
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. View Full-Text | ca_CA |
dc.description.sponsorShip | This 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.extent | 18 p. | ca_CA |
dc.format.mimetype | application/pdf | ca_CA |
dc.language.iso | eng | ca_CA |
dc.publisher | MDPI | ca_CA |
dc.relation.isPartOf | Nutrients, 2016, vol. 8, núm. 12 | ca_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.rights | Atribución 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-sa/4.0/ | * |
dc.subject | TCF7L2 | ca_CA |
dc.subject | type-2 diabetes | ca_CA |
dc.subject | Obesity | ca_CA |
dc.subject | T2D-genetic risk scores | ca_CA |
dc.subject | TCF7L2-predictive value | ca_CA |
dc.subject | PREDIMED study | ca_CA |
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 | ca_CA |
dc.type | info:eu-repo/semantics/article | ca_CA |
dc.identifier.doi | http://dx.doi.org/10.3390/nu8120793 | |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | ca_CA |
dc.relation.publisherVersion | http://www.mdpi.com/2072-6643/8/12/793 | ca_CA |
dc.type.version | info:eu-repo/semantics/publishedVersion |
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