RT Journal Article
T1 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
A1 Corella, Dolores
A1 Coltell, Oscar
A1 Sorli, Jose V.
A1 Estruch, Ramon
A1 Quiles, Laura
A1 Angel Martinez-Gonzalez, Miguel
A1 Salas-Salvado, Jordi
A1 Castaner, Olga
A1 Aros, Fernando
A1 Ortega-Calvo, Manuel
A1 Serra-Majem, Lluis
A1 Gomez-Gracia, Enrique
A1 Portoles, Olga
A1 Fiol, Miquel
A1 Diez Espino, Javier
A1 Basora, Josep
A1 Fito, Montserrat
A1 Ros, Emilio
A1 Ordovas, Jose M.
K1 TCF7L2
K1 type-2 diabetes
K1 obesity
K1 T2D-genetic risk scores
K1 TCF7L2-predictive value
K1 PREDIMED study
K1 Susceptibility loci
K1 Common variants
K1 Association
K1 Prevention
K1 Population
K1 Disease
K1 Traits
K1 Weight
AB 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.
PB Mdpi
SN 2072-6643
YR 2016
FD 2016-12-01
LK http://hdl.handle.net/10668/19310
UL http://hdl.handle.net/10668/19310
LA en
DS RISalud
RD Apr 9, 2025