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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

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Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, 46010 Valencia, Spain
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CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 28029 Madrid, Spain
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Department of Computer Languages and Systems, School of Technology and Experimental Sciences, Universitat Jaume I, 12071 Castellón, Spain
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Department of Internal Medicine, Hospital Clinic, IDIBAPS, 08036 Barcelona, Spain
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Department of Preventive Medicine and Public Health, University of Navarra—Navarra Institute for Health Research (IdisNa), 31009 Pamplona, Spain
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Human Nutrition Unit, Biochemistry and Biotechnology Department, IISPV, University Rovira i Virgili, 43003 Reus, Spain
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Cardiovascular Risk and Nutrition Research Group, Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Spain
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Department of Cardiology, Hospital Txagorritxu, 01009 Vitoria, Spain
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Department of Family Medicine, Distrito Sanitario Atención Primaria Sevilla, Centro de Salud Las Palmeritas, 41003 Sevilla, Spain
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Research Institute of Biomedical and Health Sciences, University of Las Palmas de Gran Canaria, 35001 Las Palmas de Gran Canaria, Spain
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Department of Epidemiology, School of Medicine, University of Malaga, 29071 Malaga, Spain
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Palma Institute of Health Research (IdISPa), Hospital Son Espases, 07014 Palma de Mallorca, Spain
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Department of Preventive Medicine and Public Health, University of Navarra—Navarra Institute for Health Research (IdisNA)—Servicio Navarro de Salud-Osasunbidea, 31009 Pamplona, Spain
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Lipid Clinic, Endocrinology and Nutrition Service, Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clinic, 08036 Barcelona, Spain
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Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA
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Department of Cardiovascular Epidemiology and Population Genetics, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid 28029—IMDEA Alimentación, 28049 Madrid, Spain
*
Author to whom correspondence should be addressed.
Nutrients 2016, 8(12), 793; https://doi.org/10.3390/nu8120793
Received: 23 September 2016 / Revised: 17 November 2016 / Accepted: 17 November 2016 / Published: 6 December 2016
(This article belongs to the Special Issue Nutrigenetics)
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. View Full-Text
Keywords: TCF7L2; type-2 diabetes; obesity; T2D-genetic risk scores; TCF7L2-predictive value; PREDIMED study TCF7L2; type-2 diabetes; obesity; T2D-genetic risk scores; TCF7L2-predictive value; PREDIMED study
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MDPI and ACS Style

Corella, D.; Coltell, O.; Sorlí, J.V.; Estruch, R.; Quiles, L.; Martínez-González, M.Á.; Salas-Salvadó, J.; Castañer, O.; Arós, F.; Ortega-Calvo, M.; Serra-Majem, L.; Gómez-Gracia, E.; Portolés, O.; Fiol, M.; Díez Espino, J.; Basora, J.; Fitó, M.; Ros, E.; Ordovás, J.M. 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, 8, 793. https://doi.org/10.3390/nu8120793

AMA Style

Corella D, Coltell O, Sorlí JV, Estruch R, Quiles L, Martínez-González MÁ, Salas-Salvadó J, Castañer O, Arós F, Ortega-Calvo M, Serra-Majem L, Gómez-Gracia E, Portolés O, Fiol M, Díez Espino J, Basora J, Fitó M, Ros E, Ordovás JM. 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; 8(12):793. https://doi.org/10.3390/nu8120793

Chicago/Turabian Style

Corella, Dolores, Oscar Coltell, Jose V. Sorlí, Ramón Estruch, Laura Quiles, Miguel Á. Martínez-González, Jordi Salas-Salvadó, Olga Castañer, Fernando Arós, Manuel Ortega-Calvo, Lluís Serra-Majem, Enrique Gómez-Gracia, Olga Portolés, Miquel Fiol, Javier Díez Espino, Josep Basora, Montserrat Fitó, Emilio Ros, and José M. Ordovás. 2016. "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 8, no. 12: 793. https://doi.org/10.3390/nu8120793

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