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

Corella, Dolores; Coltell, Oscar; Sorlí, José Vicente; Estruch, Ramón; Quiles, Laura; Martínez-González, Miguel Ángel, 1957-; Salas Salvadó, Jordi; Castañer, Olga; Arós, Fernando; Ortega Calvo, Manuel; Serra Majem, Lluís; Gómez-Gracia, Enrique; Portolés, Olga; Fiol, Miquel; Díez Espino, Javier; Basora, Josep; Fitó Colomer, Montserrat; Ros, Emilio; Ordovás, José M.

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

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dc.contributor.author Corella, Doloresca
dc.contributor.author Coltell, Oscarca
dc.contributor.author Sorlí, José Vicenteca
dc.contributor.author Estruch, Ramónca
dc.contributor.author Quiles, Lauraca
dc.contributor.author Martínez-González, Miguel Ángel, 1957-ca
dc.contributor.author Salas Salvadó, Jordica
dc.contributor.author Castañer, Olgaca
dc.contributor.author Arós, Fernandoca
dc.contributor.author Ortega Calvo, Manuelca
dc.contributor.author Serra Majem, Lluísca
dc.contributor.author Gómez-Gracia, Enriqueca
dc.contributor.author Portolés, Olgaca
dc.contributor.author Fiol, Miquelca
dc.contributor.author Díez Espino, Javierca
dc.contributor.author Basora, Josepca
dc.contributor.author Fitó Colomer, Montserratca
dc.contributor.author Ros, Emilioca
dc.contributor.author Ordovás, José M.ca
dc.date.accessioned 2018-02-06T09:00:12Z
dc.date.available 2018-02-06T09:00:12Z
dc.date.issued 2016
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 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
dc.format.mimetype application/pdf
dc.identifier.citation Corella D, Coltell O, Sorlí JV, Estruch R, Quiles L, Martínez-González MA. Et al. 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. 2016 Dec 6;8(12). pii: E793. DOI:10.3390/nu8120793
dc.identifier.doi http://dx.doi.org/10.3390/nu8120793
dc.identifier.issn 2072-6643
dc.identifier.uri http://hdl.handle.net/10230/33807
dc.language.iso eng
dc.publisher MDPI Publishingca
dc.relation.ispartof Nutrients. 2016 Dec 6;8(12):E793
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2009-12304
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/AGL2010-22319-C03-03
dc.rights Copyright © 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/).
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.subject.keyword PREDIMED study
dc.subject.keyword T2D-genetic risk scores
dc.subject.keyword TCF7L2
dc.subject.keyword TCF7L2-predictive value
dc.subject.keyword Obesity
dc.subject.keyword Type-2 diabetes
dc.subject.other Obesitat
dc.subject.other Diabetis
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 Scoresca
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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