1. 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
- Author
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Alimentació, Nutrició, Creixement i Salut Mental, Departament de Medicina i Cirurgia, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Jordi Salas-Salvadó; Dolores Corella; Oscar Coltell; Jose V. Sorlí; Ramón Estruch; Laura Quiles; Miguel Ángel Martínez-González; Olga Castañer; Fernando Arós ; Manuel Ortega-Calvo ; Lluís Serra-Majem ; Enrique Gómez-Gracia; Olga Portolés; Miquel Fiol; Javier Díez Espino ; Josep Basora ; Montserrat Fitó; Emilio Ros; José M. Ordovás, Alimentació, Nutrició, Creixement i Salut Mental, Departament de Medicina i Cirurgia, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, and Jordi Salas-Salvadó; Dolores Corella; Oscar Coltell; Jose V. Sorlí; Ramón Estruch; Laura Quiles; Miguel Ángel Martínez-González; Olga Castañer; Fernando Arós ; Manuel Ortega-Calvo ; Lluís Serra-Majem ; Enrique Gómez-Gracia; Olga Portolés; Miquel Fiol; Javier Díez Espino ; Josep Basora ; Montserrat Fitó; Emilio Ros; José M. Ordovás
- Abstract
DOI: 10.3390/nu8120793 URL: http://www.mdpi.com/2072-6643/8/12/793 Filiació URV: SI Inclòs a la memòria: SI FALTEN ELS ÚLTIMS CARÀCTERS DEL TÍTOL PER EXCEDIR EL LÍMIT PERMÈS!, 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.
- Published
- 2017