The ANP Genetic Variant RS5068 is Associated With a Favorable Cardiometabolic Phenotype in a Mediterranean Population

Introduction: Atrial natriuretic peptide (ANP) possesses cardiorenal protective properties including natriuresis, aldosterone suppression and vasodilation. Importantly, ANP also exerts lipolytic effects in vitro and in vivo. Previous studies reported that the ANP genetic variant rs5068 is associated with increased plasma levels of ANP, lower blood pressure values, and reduced risk of hypertension. We recently reported that in a random sample of the general population from Olmsted County, MN the G allele of rs5068 was associated with increased levels of ANP, lower blood pressure and BMI, waist circumference, reduced prevalence of obesity and metabolic syndrome. To date, these associations have not been replicated. Hypothesis: The minor allele of rs5068 is associated with a favorable cardiometabolic phenotype in 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/m2, 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.