Mediterranean Diet Reduces the Adverse Effect of the TCF7L2-rs7903146 Polymorphism on Cardiovascular Risk Factors and Stroke Incidence

Mediterranean Diet Reduces the Adverse Effect of the TCF7L2-rs7903146 Polymorphism on Cardiovascular Risk Factors and Stroke Incidence

A randomized controlled trial in a high-cardiovascular-risk population

1. Dolores Corella, DPHARM, PHD¹,²⇑,
2. Paula Carrasco, BSC, PHD¹,²,
3. Jose V. Sorlí, MD, PHD¹,²,
4. Ramón Estruch, MD, PHD²,³,
5. Jesús Rico-Sanz, PHD¹,
6. Miguel Ángel Martínez-González, MD, PHD²,⁴,
7. Jordi Salas-Salvadó, MD, PHD²,⁵,
8. M. Isabel Covas, DPHARM, PHD²,⁶,
9. Oscar Coltell, MSC, PHD²,⁷,
10. Fernando Arós, MD, PHD²,⁸,
11. José Lapetra, MD, PHD²,⁹,
12. Lluís Serra-Majem, MD, PHD²,¹⁰,
13. Valentina Ruíz-Guiterrez, PHD²,¹¹,
14. Julia Warnberg, PHD¹²,
15. Miquel Fiol, MD, PHD²,¹³,
16. Xavier Pintó, MD, PHD²,¹⁴,
17. Carolina Ortega-Azorín, PHD¹,²,
18. Miguel Ángel Muñoz, MD, PHD¹⁵,
19. J. Alfredo Martínez, DPHARM, MD, PHD²,¹⁶,
20. Enrique Gómez-Gracia, MD, PHD²,¹²,
21. José I. González, PHD¹,²,
22. Emilio Ros, MD, PHD²,¹⁷ and
23. José M. Ordovás, PHD¹⁸,¹⁹,²⁰

+ Author Affiliations

1. ¹Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, Valencia, Spain
2. ²CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
3. ³Department of Internal Medicine, Hospital Clinic, Institut d’Investigacions Biomèdiques August Pi Sunyer, Barcelona, Spain
4. ⁴Department of Preventive Medicine and Public Health, School of Medicine, University of Navarra, Madrid, Spain
5. ⁵Human Nutrition Unit, Faculty of Medicine, Institut d’Investigació Sanitària Pere Virgili, University Rovira i Virgili, Reus, Spain
6. ⁶Cardiovascular Epidemiology Unit, Municipal Institut for Medical Research, Barcelona, Spain
7. ⁷Department of Computer Languages and Systems, School of Technology and Experimental Sciences, Jaume I University, Castellón, Spain
8. ⁸Department of Cardiology, Hospital Txagorritxu, Vitoria, Spain
9. ⁹Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain
10. ¹⁰Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain
11. ¹¹Instituto de la Grasa, Consejo Superior de Investigaciones Científicas, Sevilla, Spain
12. ¹²Department of Epidemiology, School of Medicine, University of Malaga, Malaga, Spain
13. ¹³University Institute for Health Sciences Investigation, Hospital Son Dureta, Palma de Mallorca, Isla Baleares, Spain
14. ¹⁴Lipids and Vascular Risk Unit, Internal Medicine, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain
15. ¹⁵Primary Care Division, Catalan Institute of Health, Barcelona, Spain
16. ¹⁶Department of Nutrition, Food Science, Physiology and Toxicology, University of Navarra, Pamplona, Spain
17. ¹⁷Lipid Clinic, Endocrinology and Nutrition Service, Institut d’Investigacions Biomèdiques August Pi Sunyer, Hospital Clinic, Barcelona, Spain
18. ¹⁸Department of Cardiovascular Epidemiology and Population Genetics, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain
19. ¹⁹Institutos Madrileños of Estudios Avanzados Alimentación, Madrid, Spain
20. ²⁰Nutrition and Genomics Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts

1. Corresponding author: Dolores Corella, dolores.corella@uv.es.

Abstract

OBJECTIVE Transcription factor 7-like 2 (TCF7L2) polymorphisms are strongly associated with type 2 diabetes, but controversially with plasma lipids and cardiovascular disease. Interactions of the Mediterranean diet (MedDiet) on these associations are unknown. We investigated whether the TCF7L2-rs7903146 (C>T) polymorphism associations with type 2 diabetes, glucose, lipids, and cardiovascular disease incidence were modulated by MedDiet.

RESEARCH DESIGN AND METHODS A randomized trial (two MedDiet intervention groups and a control group) on 7,018 participants in the PREvención con DIetaMEDiterránea study was undertaken and major cardiovascular events assessed. Data were analyzed at baseline and after a median follow-up of 4.8 years. Multivariable-adjusted Cox regression was used to estimate hazard ratios (HR) for cardiovascular events.

RESULTS The TCF7L2-rs7903146 polymorphism was associated with type 2 diabetes (odds ratio 1.87 [95% CI 1.62–2.17] for TT compared with CC). MedDiet interacted significantly with rs7903146 on fasting glucose at baseline (P interaction = 0.004). When adherence to the MedDiet was low, TT had higher fasting glucose concentrations (132.3 ± 3.5 mg/dL) than CC+CT (127.3 ± 3.2 mg/dL) individuals (P = 0.001). Nevertheless, when adherence was high, this increase was not observed (P = 0.605). This modulation was also detected for total cholesterol, LDL cholesterol, and triglycerides (P interaction < 0.05 for all). Likewise, in the randomized trial, TT subjects had a higher stroke incidence in the control group (adjusted HR 2.91 [95% CI 1.36–6.19]; P = 0.006 compared with CC), whereas dietary intervention with MedDiet reduced stroke incidence in TT homozygotes (adjusted HR 0.96 [95% CI 0.49–1.87]; P = 0.892 for TT compared with CC).

CONCLUSIONS Our novel results suggest that MedDiet may not only reduce increased fasting glucose and lipids in TT individuals, but also stroke incidence.

• Received April 22, 2013.
• Accepted June 17, 2013.

• © 2013 by the American Diabetes Association.

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