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
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
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| Enthalten in: |
Nutrients - 8(2016), 12 vom: 06. Dez. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Corella, Dolores [VerfasserIn] |
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| Anmerkungen: |
Date Completed 03.04.2017 Date Revised 13.11.2018 published: Electronic Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a 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 |b Time for Obesity-Specific Genetic Risk Scores |
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| 500 | |a Date Completed 03.04.2017 | ||
| 500 | |a Date Revised 13.11.2018 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a PREDIMED study | |
| 650 | 4 | |a T2D-genetic risk scores | |
| 650 | 4 | |a TCF7L2 | |
| 650 | 4 | |a TCF7L2-predictive value | |
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| 650 | 4 | |a type-2 diabetes | |
| 650 | 7 | |a Genetic Markers |2 NLM | |
| 650 | 7 | |a TCF7L2 protein, human |2 NLM | |
| 650 | 7 | |a Transcription Factor 7-Like 2 Protein |2 NLM | |
| 700 | 1 | |a Coltell, Oscar |e verfasserin |4 aut | |
| 700 | 1 | |a Sorlí, Jose V |e verfasserin |4 aut | |
| 700 | 1 | |a Estruch, Ramón |e verfasserin |4 aut | |
| 700 | 1 | |a Quiles, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Martínez-González, Miguel Ángel |e verfasserin |4 aut | |
| 700 | 1 | |a Salas-Salvadó, Jordi |e verfasserin |4 aut | |
| 700 | 1 | |a Castañer, Olga |e verfasserin |4 aut | |
| 700 | 1 | |a Arós, Fernando |e verfasserin |4 aut | |
| 700 | 1 | |a Ortega-Calvo, Manuel |e verfasserin |4 aut | |
| 700 | 1 | |a Serra-Majem, Lluís |e verfasserin |4 aut | |
| 700 | 1 | |a Gómez-Gracia, Enrique |e verfasserin |4 aut | |
| 700 | 1 | |a Portolés, Olga |e verfasserin |4 aut | |
| 700 | 1 | |a Fiol, Miquel |e verfasserin |4 aut | |
| 700 | 1 | |a Díez Espino, Javier |e verfasserin |4 aut | |
| 700 | 1 | |a Basora, Josep |e verfasserin |4 aut | |
| 700 | 1 | |a Fitó, Montserrat |e verfasserin |4 aut | |
| 700 | 1 | |a Ros, Emilio |e verfasserin |4 aut | |
| 700 | 1 | |a Ordovás, José M |e verfasserin |4 aut | |
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