Grant: Project Grant

Diet is a major aspect of the environment that can be targeted in preventing cardiometabolic diseases. However, the effect of dietary changes on the cardiometabolic risk profile differs significantly between individuals. In a nutritional intervention, we have observed the hypotriglyceridemic effect of omega-3 fatty acids of marine origine in the entire cohort. However, the plasma triglyceride response was highly heterogeneous with 28.8% of individuals being considered as non-responders since no decrease in plasma triglyceride levels was observed after the supplementation despite compliance to the protocol. These results suggest that intrinsic characteristics of study participants such as genetic factors are likely to influence the plasma lipid response to diet. Accordingly, we have shown that genetic variations within genes modulated by omega-3 fatty acids explain, at least partly, the heterogeneity of the plasma triglyceride response to omega-3 fatty acids. We performed a genome wide association study and identified loci with significant differences in allele frequency between responders and non-responders to the omega-3 fatty acid supplementation. In the present research program, we wish to pursue the identification of genetic factors explaining the heterogeneity of the plasma TG response by increasing the density of genetic markers in the loci previously identified and to demonstrate the potential functional significance of these polymorphisms.