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Nutrients 2016, 8(12), 793; doi:10.3390/nu8120793

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

1
Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, 46010 Valencia, Spain
2
CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 28029 Madrid, Spain
3
Department of Computer Languages and Systems, School of Technology and Experimental Sciences, Universitat Jaume I, 12071 Castellón, Spain
4
Department of Internal Medicine, Hospital Clinic, IDIBAPS, 08036 Barcelona, Spain
5
Department of Preventive Medicine and Public Health, University of Navarra—Navarra Institute for Health Research (IdisNa), 31009 Pamplona, Spain
6
Human Nutrition Unit, Biochemistry and Biotechnology Department, IISPV, University Rovira i Virgili, 43003 Reus, Spain
7
Cardiovascular Risk and Nutrition Research Group, Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Spain
8
Department of Cardiology, Hospital Txagorritxu, 01009 Vitoria, Spain
9
Department of Family Medicine, Distrito Sanitario Atención Primaria Sevilla, Centro de Salud Las Palmeritas, 41003 Sevilla, Spain
10
Research Institute of Biomedical and Health Sciences, University of Las Palmas de Gran Canaria, 35001 Las Palmas de Gran Canaria, Spain
11
Department of Epidemiology, School of Medicine, University of Malaga, 29071 Malaga, Spain
12
Palma Institute of Health Research (IdISPa), Hospital Son Espases, 07014 Palma de Mallorca, Spain
13
Department of Preventive Medicine and Public Health, University of Navarra—Navarra Institute for Health Research (IdisNA)—Servicio Navarro de Salud-Osasunbidea, 31009 Pamplona, Spain
14
Lipid Clinic, Endocrinology and Nutrition Service, Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clinic, 08036 Barcelona, Spain
15
Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA
16
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.
Received: 23 September 2016 / Revised: 17 November 2016 / Accepted: 17 November 2016 / Published: 6 December 2016
(This article belongs to the Special Issue Nutrigenetics)
View Full-Text   |   Download PDF [1864 KB, uploaded 6 December 2016]   |  

Abstract

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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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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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.

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