a randomly selected Mediterranean population. Methods: We genotyped a well characterized random sample of the residents of Ventimiglia di Sicilia, a small town in Sicily. Results: Genotype frequencies of rs5068 were AA: 93.5%, AG: 6.4%, and GG: 0.1%. All subsequent analyses are AA vs AG+GG. After adjusting for age and gender, the minor G allele was associated with lower systolic (120624 vs 126621 mmHg, p50.003) and diastolic (72610 vs 76610 mmHg, p50.03) blood pressure and lower BMI (26.764.9 vs 28.265.7 kg/m, p50.04). Male subjects presenting HDL cholesterol plasma levels!40 mg/dL were less frequent in the AG+GG group (17% vs 27%,p50.05). Importantly, the G allele was significantly associated with a lower prevalence of metabolic syndrome (19% vs 32%, p50.02). Conclusions: The association between the minor allele of rs5068 and a favorable cardiometabolic phenotype, that we previously showed in a US population, is now replicated in a Mediterranean population in which the G allele of rs5068 is associated with lower blood pressure values, BMI, and prevalence of metabolic syndrome. These findings may lead to a diagnostic strategy to assess cardiometabolic risk and also lay the foundation for future development of an ANP or ANP-like therapy for metabolic syndrome.