2026-08-29T08:18:55Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/51722024-11-28T18:07:02Zcom_20.500.12105_19604com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19605col_20.500.12105_16961col_20.500.12105_16967col_20.500.12105_16968col_20.500.12105_16983
Repisalud
author
Corella, Dolores
author
Coltell, Oscar
author
Sorli, Jose V.
author
Estruch, Ramon
author
Quiles, Laura
author
Angel Martinez-Gonzalez, Miguel
author
Salas-Salvado, Jordi
author
Castaner, Olga
author
Aros, Fernando
author
Ortega-Calvo, Manuel
author
Serra-Majem, Lluis
author
Gomez-Gracia, Enrique
author
Portoles, Olga
author
Fiol, Miquel
author
Diez Espino, Javier
author
Basora, Josep
author
Fito, Montserrat
author
Ros, Emilio
author
Ordovas, Jose M
funder
Instituto de Salud Carlos III
funder
Ministerio de Economía y Competitividad (España)
funder
Jaume I University (España)
funder
Generalitat Valenciana (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
United States Department of Agriculture. Agricultural Research Service
2017-10-20T10:33:51Z
2017-10-20T10:33:51Z
2016
Nutrients. 2016; 8(12):793
10.3390/nu8120793
2072-6643
Nutrients
http://hdl.handle.net/20.500.13003/10080
27929407
L613545861
2-s2.0-85003946080
http://hdl.handle.net/20.500.12105/5172
389144100041
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.
eng
TCF7L2
Type-2 diabetes
Obesity
T2D-genetic risk scores
TCF7L2-predictive value
PREDIMED study
SUSCEPTIBILITY LOCI
MEDITERRANEAN DIET
INSULIN-RESISTANCE
COMMON VARIANTS
BODY-FAT
ASSOCIATION
POPULATION
PREVENTION
TRIAL
MASS
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
research article
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PolymorphismOfTheTranscriptionFactor_2016.pdf
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e2c3efcb4735c78aeccc2b8470626103
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PolymorphismOfTheTranscriptionFactor_2016.pdf.txt
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e2c3efcb4735c78aeccc2b8470626103
88744
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PolymorphismOfTheTranscriptionFactor_2016.pdf.txt