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. José M. Ordovás, PHD18,19,20
  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{at}


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.

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