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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 | Authors: | Corella, Dolores Coltell, Oscar Sorlí, José V. Estruch, Ramón Quiles, L. Martínez-González, Miguel Ángel Salas-Salvadó, Jordi Castañer, O. Arós, Fernando Ortega-Calvo, M. Serra Majem, Luis Gómez-Gracia, Enrique Portolés, O. Fiol, M. Díez Espino, J. Basora, J. Fitó, M. Ros, Emilio Ordovás, J.M. |
UNESCO Clasification: | 3206 Ciencias de la nutrición | Keywords: | Obesity PREDIMED study T2D-genetic risk scores TCF7L2 TCF7L2-predictive value, et al |
Issue Date: | 2016 | Journal: | Nutrients | 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. | URI: | http://hdl.handle.net/10553/41364 | ISSN: | 2072-6643 | DOI: | 10.3390/nu8120793 | Source: | Nutrients [ISSN 2072-6643], v. 8 (12), article number 793 |
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