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.
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.


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.
Corresponding author: Dolores Corella, dolores.corella@uv.es.
Dolores
D
Corella
Paula
P
Carrasco
Jose V
JV
Sorlí
Ramón
R
Estruch
Jesús
J
Rico-Sanz
Miguel Ángel
MÁ
Martínez-González
Jordi
J
Salas-Salvadó
M Isabel
MI
Covas
Oscar
O
Coltell
Fernando
F
Arós
José
J
Lapetra
Lluís
L
Serra-Majem
Valentina
V
Ruiz-Gutiérrez
Julia
J
Warnberg
Miquel
M
Fiol
Xavier
X
Pintó
Carolina
C
Ortega-Azorín
Miguel Ángel
MÁ
Muñoz
J Alfredo
JA
Martínez
Enrique
E
Gómez-Gracia
José I
JI
González
Emilio
E
Ros
José M
JM
Ordovás
D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D038441:Diet, Mediterranean; D005215:Fasting / Q000097:blood; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012307:Risk Factors; D020521:Stroke / Q000196:embryology* / Q000517:prevention & control; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics*; D014280:Triglycerides / Q000097:blood
D058118:Transcription Factor 7-Like 2 Protein; D014280:Triglycerides