NOS3 Glu298Asp Polymorphism Interacts with Virgin Olive Oil Phenols to Determine the Postprandial Endothelial Function in Patients with the Metabolic Syndrome

Background: Glu298Asp polymorphism of the endothelial nitric oxide synthase (eNOS) gene (NOS3) has been characterized as a risk factor of hypertension and coronary artery disease. Previous studies suggest that the higher risk observed in T allele carriers is due to endothelial dysfunction associated with a lower eNOS activity and that acute consumption of phenol-rich olive oil ameliorates postprandial endothelial dysfunction by reducing oxidative stress and increasing nitric oxide bioavailability. Nevertheless, how these facts may interact in a population with altered endothelial function such as metabolic syndrome patients remains unknown. Objective: The objective of the study was to evaluate whether the presence of NOS3 Glu298Asp polymorphism interacts with the phenol content of virgin olive oil (VOO) to influence postprandial endothelial function. Design: Fifty-seven subjects with metabolic syndrome received three breakfasts based on VOO with different phenolic content. Baseline, incremental area under the curve, peak, and maximum parameters of postocclusive skin reactive hyperemia (PORH) were evaluated by laser Doppler, and the nitrate/nitrite [NO(x)] and eNOS concentrations were obtained during fasting and postprandially. Results: A gene-diet interaction was found on maximum PORH and NO(x) (P = 0.039 and P = 0.043, respectively). TT subjects showed lower values of eNOS, NO(x), and maximum PORH as compared with GG and GT subjects, especially in the postprandial measurements (all P < 0.05). However, most of these differences were attenuated when high-phenol VOO was consumed. Conclusion: In a population with a compromised endothelial function, concentrations of phenols in dietary VOO interact with NOS3 Glu298Asp to ameliorate the endothelial dysfunction associated to the TT genotype. (J Clin Endocrinol Metab 96: E1694-E1702, 2011)