Nutrigenetics and nutrigenomics of atherosclerosis

The latest genome-wide association studies (GWAS) have re-energized our effort to understand the genetic basis of atherosclerotic cardiovascular disease. Although the knowledge generated by GWAS has confirmed that mediators of inflammation and perturbed lipid metabolism are major players in cardiovascular disease (CVD) development, much of individual disease heritability remains unexplained by the variants identified through GWAS. Moreover, results from interventions that aim at the pharmaceutical modification of lipid parameters fall short of expectation. These elusive treatment goals based on heritability studies highlight a key supportive, and perhaps even primary, role of nutritional therapy to achieve better health outcomes. Nonetheless, effective and specific interventions for CVD prevention using principles of "personalized" nutrition require a better knowledge of gene-diet interactions, an area that remains poorly explored. Dietary fatty acids such as omega-3 polyunsaturated fatty acids (PUFAs) are an excellent example of a widely studied "environment" that interacts with the genetic makeup in relation to CVD. A thorough exploration of the nutrigenomics and nutrigenetics of omega-3 PUFAs is key to understanding the etiology, and developing effective preventive measures. In this review, we will summarize the current state of knowledge of genetic interactions with omega-3 PUFAs in modulating lipid metabolism and inflammation, and defining health outcomes. Nutrigenetics and nutrigenomics are still in their infancy with respect to CVD prediction and therapy. Integration of the progress in the omics, including metabolomics, lipidomics, transcriptomics, and proteomics, coupled with advances in nutrigenomic and nutrigenetic research will move us towards personalized medicine as the ultimate paradigm of responsible clinical practice.