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

Introduction: Atrial natriuretic peptide (ANP) possesses cardiorenal protective propertiesincluding natriuresis, aldosterone suppression and vasodilation. Importantly,ANP also exerts lipolytic effects in vitro and in vivo. Previous studies reported thatthe ANP genetic variant rs5068 is associated with increased plasma levels of ANP,lower blood pressure values, and reduced risk of hypertension. We recently reportedthat in a random sample of the general population from Olmsted County, MN the Gallele of rs5068 was associated with increased levels of ANP, lower blood pressureand BMI, waist circumference, reduced prevalence of obesity and metabolic syndrome.To date, these associations have not been replicated. Hypothesis: The minorallele of rs5068 is associated with a favorable cardiometabolic phenotype in a randomly selected Mediterranean population. Methods: We genotyped a well characterizedrandom sample of the residents of Ventimiglia di Sicilia, a small town inSicily. Results: Genotype frequencies of rs5068 were AA: 93.5%, AG: 6.4%, andGG: 0.1%. All subsequent analyses are AA vs AG+GG. After adjusting for ageand gender, the minor G allele was associated with lower systolic (120624 vs126621 mmHg, p50.003) and diastolic (72610 vs 76610 mmHg, p50.03) bloodpressure and lower BMI (26.764.9 vs 28.265.7 kg/m2, p50.04). Male subjects presentingHDL cholesterol plasma levels!40 mg/dL were less frequent in the AG+GGgroup (17% vs 27%,p50.05). Importantly, the G allele was significantly associatedwith a lower prevalence of metabolic syndrome (19% vs 32%, p50.02). Conclusions:The association between the minor allele of rs5068 and a favorable cardiometabolicphenotype, that we previously showed in a US population, is now replicated ina Mediterranean population in which the G allele of rs5068 is associated with lowerblood pressure values, BMI, and prevalence of metabolic syndrome. These findingsmay lead to a diagnostic strategy to assess cardiometabolic risk and also lay the foundationfor future development of an ANP or ANP-like therapy for metabolicsyndrome.