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

Dolores Corella, Paula Carrasco, Jose V Sorlí, Ramón Estruch, Jesús Rico-Sanz, Miguel Ángel Martínez-González, Jordi Salas-Salvadó, M Isabel Covas, Oscar Coltell, Fernando Arós, José Lapetra, Lluís Serra-Majem, Valentina Ruiz-Gutiérrez, Julia Warnberg, Miquel Fiol, Xavier Pintó, Carolina Ortega-Azorín, Miguel Ángel Muñoz, J Alfredo Martínez, Enrique Gómez-Gracia, José I González, Emilio Ros, José M Ordovás, Dolores Corella, Paula Carrasco, Jose V Sorlí, Ramón Estruch, Jesús Rico-Sanz, Miguel Ángel Martínez-González, Jordi Salas-Salvadó, M Isabel Covas, Oscar Coltell, Fernando Arós, José Lapetra, Lluís Serra-Majem, Valentina Ruiz-Gutiérrez, Julia Warnberg, Miquel Fiol, Xavier Pintó, Carolina Ortega-Azorín, Miguel Ángel Muñoz, J Alfredo Martínez, Enrique Gómez-Gracia, José I González, Emilio Ros, José M Ordovás

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) with 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 (HRs) 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.

Figures

Figure 1
Figure 1
Cumulative stroke free-survival by TCF7L2-rs7903146 genotypes in the control group (A) (n = 2,291) and in the MedDiet intervention groups (B) (n = 4,827). Cox regression models with outcome of stroke and the TCF7L2-rs7903146 polymorphism (CC, CT, and TT) adjusted by sex, age, center, type 2 diabetes, BMI, intervention group, alcohol, smoking, total energy intake, and adherence to the MedDiet at baseline. The P values for the TCF7L2 polymorphism and for the corresponding genotypes (CT vs. CC or TT vs. CC) were obtained in the multivariable adjusted models.

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