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 varian...
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| Language: | spa |
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2017
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| Online Access: | https://hdl.handle.net/10171/43266 |
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| author | Ordovas, J.M. (Jose Maria) Ros, E. (Emilio) Fito, M. (Montserrat) Basora, J. (Josep) Diez-Espino, J. (Javier) Fiol, M. (Miquel) Portoles, O. (Olga) Gomez-Gracia, E. (Enrique) Serra-Majem, L. (Luis) Ortega-Calvo, M. (Manuel) Martinez-Gonzalez, M.A. (Miguel Ángel) Quiles, L. (Laura) Estruch, R. (Ramón) Sorli, J.V. (Jose V.) Coltell, O. (Oscar) Corella, D. (Dolores) |
| author_facet | Ordovas, J.M. (Jose Maria) Ros, E. (Emilio) Fito, M. (Montserrat) Basora, J. (Josep) Diez-Espino, J. (Javier) Fiol, M. (Miquel) Portoles, O. (Olga) Gomez-Gracia, E. (Enrique) Serra-Majem, L. (Luis) Ortega-Calvo, M. (Manuel) Martinez-Gonzalez, M.A. (Miguel Ángel) Quiles, L. (Laura) Estruch, R. (Ramón) Sorli, J.V. (Jose V.) Coltell, O. (Oscar) Corella, D. (Dolores) |
| author_sort | Ordovas, J.M. (Jose Maria) |
| collection | DSpace |
| description | 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. |
| format | info:eu-repo/semantics/article |
| id | oai:dadun.unav.edu:10171-43266 |
| institution | Universidad de Navarra |
| language | spa |
| publishDate | 2017 |
| publisher | MDPI |
| record_format | dspace |
| spelling | oai:dadun.unav.edu:10171-432662023-03-13T11:03:59Z 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 Ordovas, J.M. (Jose Maria) Ros, E. (Emilio) Fito, M. (Montserrat) Basora, J. (Josep) Diez-Espino, J. (Javier) Fiol, M. (Miquel) Portoles, O. (Olga) Gomez-Gracia, E. (Enrique) Serra-Majem, L. (Luis) Ortega-Calvo, M. (Manuel) Martinez-Gonzalez, M.A. (Miguel Ángel) Quiles, L. (Laura) Estruch, R. (Ramón) Sorli, J.V. (Jose V.) Coltell, O. (Oscar) Corella, D. (Dolores) PREDIMED study TCF7L2-predictive value T2D-genetic risk scores Obesity Type-2 diabetes TCF7L2 Materias Investigacion::Ciencias de la Salud::Salud pública 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. 2017-05-02T09:49:18Z 2017-05-02T09:49:18Z 2016 info:eu-repo/semantics/article https://hdl.handle.net/10171/43266 spa info:eu-repo/semantics/openAccess application/pdf MDPI |
| spellingShingle | PREDIMED study TCF7L2-predictive value T2D-genetic risk scores Obesity Type-2 diabetes TCF7L2 Materias Investigacion::Ciencias de la Salud::Salud pública Ordovas, J.M. (Jose Maria) Ros, E. (Emilio) Fito, M. (Montserrat) Basora, J. (Josep) Diez-Espino, J. (Javier) Fiol, M. (Miquel) Portoles, O. (Olga) Gomez-Gracia, E. (Enrique) Serra-Majem, L. (Luis) Ortega-Calvo, M. (Manuel) Martinez-Gonzalez, M.A. (Miguel Ángel) Quiles, L. (Laura) Estruch, R. (Ramón) Sorli, J.V. (Jose V.) Coltell, O. (Oscar) Corella, D. (Dolores) 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 |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | PREDIMED study TCF7L2-predictive value T2D-genetic risk scores Obesity Type-2 diabetes TCF7L2 Materias Investigacion::Ciencias de la Salud::Salud pública |
| url | https://hdl.handle.net/10171/43266 |
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