The MetS, a cluster of metabolic abnormalities, is of interest from a public health perspective because early intervention amongst these individuals may prevent the development of serious health complications such as diabetes (DM). The prevalence of MetS is 20–30% among adult populations in most countries, and individuals with the MetS have a 6-fold increased risk of DM. Atherogenic dyslipidemia is also involved in the pathogenesis of DM because insulin regulates several of the steps of lipid metabolism. To understand the progression of the disease, it is necessary to consider both candidate genes for involvement, as well as factors related to the advancing age or the environment, diet and lifestyle.Genomics and epigenomics are revolutionizing biomedical research areas that can hopefully decipher some of the gaps in our current knowledge of cardiovascular risk factors. This proposal aims at studying the possible interactions among several candidate genes for MetS-related traits or DM using a genetic predisposition score (GPS), the adherence to the Mediterranean dietary pattern and the risk to develop MetS as well as the influence of classical and new biomarkers related to MetS-traits, in order to prevent/delay the onset of MetS in a European population. It also aims at studying the replication of these gene-diet interactions in different American populations. Furthermore, this proposal aims to examine the expression of microRNAs related to cholesterol and lipoprotein metabolism in the enterocyte cell line; and to dissect the influence of dietary polyphenols (important components of a Mediterranean dietary pattern) and other bioactive food components on the expression of microRNAs related to cholesterol and lipoprotein metabolism as strategy to manage dyslipidemia.This project will address the translation of this knowledge into clinical practice and public health recommendations for the prevention and therapy of the pre-diabetes phase of the MetS and dyslipidemia.