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

Abstract

OBJECTIVETranscription 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 METHODSA 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.RESULTSThe 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).CONCLUSIONSOur novel results suggest that MedDiet may not only reduce increased fasting glucose and lipids in TT individuals, but also stroke incidence.

Living long and ageing well: is epigenomics the missing link between nature and nurture?

“…Carriers of the less common allele, T-allele of TCF7L2 gene polymorphism (rs7903146, intron 4, C [ T) are at higher risk of developing type 2 diabetes, with this allele being associated with hyperglycaemia, hypercholesteraemia, hypertriglyceridaemia and increased cardiovascular disease compared with C and CT carriers (Sousa et al 2009). In the PREDIMED study, an apparent gene-environment interaction was identified for T allele carriers since their metabolic risk was much ameliorated by high compliance with the Mediterranean diet so that glucose, cholesterol and triglycerides were normalised and their diabetes risk reduced to match C-allele carriers in the follow-up period (Corella et al 2013;Estruch et al 2006). Furthermore TT-genotype carriers in the control group demonstrated higher incidence of stroke at 5 years follow-up, whereas TT-carriers, who maintained high compliance with Mediterranean diet, removed their increased stroke risk almost completely (Corella et al 2013).…”

Nutrigenomics, the Microbiome, and Gene-Environment Interactions: New Directions in Cardiovascular Disease Research, Prevention, and Treatment

“…For example, variation in the TCF7L2 gene, previously implicated in type 2 diabetes mellitus, 69 was shown to interact with diet through intervention with the Mediterranean diet and played a role in determining stroke risk. 34 The effects of other loci such as 9p21 and FTO, which are robustly associated with CVD and obesity, respectively, have also been reported to modulate CVD risk through interaction with diet. 44,70 Gene-diet relationships are complex, with multiple dietary components potentially interacting with genotype to determine CVD risk.…”

How calorie-focused thinking about obesity and related diseases may mislead and harm public health. An alternative

“…Indeed, higher-calorie fattier foods and higher-fat diets may produce and sustain as much or more weight loss than calorie-restricted or higher-carbohydrate diets (9,10,89-98) -particularly among those already having metabolic abnormalities (93,94,99) . Moreover, certain fattier/lower-carbohydrate diets may also be associated with favourable metabolic indicators (10,89,(91)(92)(93)(94)(98)(99)(100)(101)(102)(103)(104)(105)(106)(107)(108)(109) , reduced adverse health events (69,102,110,111) and delayed mortality (110)(111)(112)(113) .…”