Effects of dietary components on cardiovascular disease risk factors and their interaction with candidate genes

Introduction: Plants-rich diets have been consistently associated with protective effects on Cardiovascular Disease (CVD), in particular a significant body of evidence underlines the effects of vegetarian diet and Mediterranean diets on LDL and total cholesterol levels. It has been postulated that modifications are the effect of decreased dietary absorption of cholesterol and/or decreased synthesis. In addition the large individual variability in the response to diet-induced changes in cholesterol levels could be related to interaction between genes involved in cholesterol metabolism and dietary factors. Aim and objectives: In the context of the ATHENA study (7FP), we explored the effects of dietary components, particularly anthocyanins and polyphenols, on CVD risk factors and the possible molecular mechanisms underlying inter-individuals variability in the response to diet. Methods: We recruited 450 apparently healthy volunteers. We collected demographic, clinical, dietary, biochemical and genetic data. Macro and micro nutrients intake was estimated through 24 hour dietary interview repeated at least twice to get seasonal variations. Overall dietary patterns (vegetarian/omnivore) were self-reported while adherence to Mediterranean diet was evaluated through a questionnaire. We analyzed the association between non-cholesterol sterols which are implicated in cholesterol homeostasis and dietary components using multiparametric regression models. We explored Gene*Environment (G*E) interactions, on five candidate genes previously reported in nutrigenomic studies or encoding proteins modulated by diet: for LDL (CYP7A1, INSIG2, LPA, PCSK9) and for HDL (PON1). In addition we developed a tool to manage nutrigenomic studies that includes a web-platform and a mHealth app. Results: Individuals with plants-rich diets (i.e. vegetarians, those with high adherence to Mediterranean diet and those with high polyphenols intake) had lower BMI and lower blood pressure compared to individuals with low-plants diets. Vegetarians showed decreased total cholesterol and LDL levels. Phytosterols were significantly increased in plants-rich diets. Lathosterol was significantly decreased in relation to adherence to Mediterranean diet. 27-hydroxycholesterol (27OHC) levels resulted increased in all plants-rich diets. Four independent SNPs of PON1 were shown to modulate the activity of polyphenols/anthocyanins on CVD risk factors. A SNP of PCSK9, already reported in relation to a “gain of function” mutation showed interaction with overall diet in determining LDL plasma levels. Discussion: Our study showed that plant-rich diets increase the cholesterol turnover in the peripheral tissues. This mechanism, combined with already reported modifications in the absorption of cholesterol and decrease de novo synthesis, can contribute to the widely recognized beneficial effects of plant-rich diets on cholesterol levels. The results reported for G*E interactions of PON1 and PCSK9 genes with dietary factors in modifying the lipid profile warrant replication. The mHealth solution implemented, delivering semi-automatic suggestions, based on the outputs of a Decision Support System than needs to be validated by healthcare professionals before being displayed at patient side, offers the possibility to track the patient lifestyles and to collect valuable information for nutritional and nutrigenetic studies.