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
Palabras clave : 
PREDIMED study
TCF7L2-predictive value
T2D-genetic risk scores
Obesity
Type-2 diabetes
TCF7L2
Materias Investigacion::Ciencias de la Salud::Salud pública
Fecha de publicación: 
2016
Editorial : 
MDPI
ISSN: 
2072-6643
Nota: 
Creative Commons Attribution License 4.0
Cita: 
Corella D., Coltell O., Sorlí J. V., Estruch R., Quiles L, Martinez-Gonzalez, M. A., 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;8(12):793.
Resumen
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.

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Fichero: 
nutrients-08-00793.pdf
Descripción: 
Tamaño: 
1,13 MB
Formato: 
Adobe PDF


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