A Genetic Variant of the Atrial Natriuretic Peptide Gene Is Associated With Cardiometabolic Protection in the General Community

Abstract

Objectives We sought to define the cardiometabolic phenotype associated with rs5068, a genetic variant of the atrial natriuretic peptide (ANP) gene. Background ANP and BNP play an important role in cardiorenal homeostasis but also exert metabolic actions. Methods We genotyped 1608 randomly selected residents from Olmsted County, Minnesota, USA. Subjects were well characterized. Results Genotype frequencies were: AA 89.9%, AG 9.7%, and GG 0.4%; all subsequent analyses were AA vs AG+GG. After adjustment for age and gender the G allele was associated with increased plasma levels of N-terminal-proANP (NT-proANP) (p=0.002). The minor allele was also associated with lower BMI (p=0.006), prevalence of obesity (p=0.002), waist circumference (p=0.021), lower levels of C-reactive protein (p=0.027) and higher values of HDL cholesterol (p=0.019). The AG+GG group had a lower systolic blood pressure (p=0.011) and lower prevalence of myocardial infarction (p=0.042). The minor allele was associated with a lower prevalence of metabolic syndrome (p=0.025). After adjusting for BMI the association between the G allele and HDL cholesterol, C – reactive protein values, myocardial infarction and metabolic syndrome was not significant; the association with systolic blood pressure, BMI, obesity, waist circumference remained significant even after adjusting for NT-proANP. Conclusions In a random sample of the general US population the minor allele of rs5068 is associated with a favorable cardiometabolic profile. These findings suggest that rs5068 or genetic loci in linkage disequilibrium may affect susceptibility for cardiometabolic diseases and support the possible protective role of natriuretic peptides by their favorable effects on metabolic function. Replication studies are needed to confirm our findings.

Atrial Natriuretic Peptide ― Old But New Therapeutic in Cardiovascular Diseases ―

“…Following this study, we reported that the rs5068 allele was associated with increased NT-proANP levels, lower body mass index, C-reactive protein levels, BP, and waist circumference, with higher levels of high-density lipoprotein cholesterol (HDL-C) and a lower prevalence of MI and MetS in the general community of Olmsted County, MN. 26 We confirmed these findings in a general population study of Italians. 27 In addition, Jujic et al reported that 27,307 French non-diabetic individuals with the rs5068 minor allele had a lower incidence of diabetes within 14 years.…”

M-Atrial Natriuretic Peptide: A Novel Antihypertensive Protein Therapy

“…Further, human studies from NewtonCheh and coworkers have recently reported genetic variants of the ANP gene, which result in increased circulating ANP and are associated with lower BP and a reduced risk of hypertension [25, 26•]. Recent studies from Olmsted County, Minnesota, confirm the studies of Newton-Cheh demonstrating that the ANP genetic variant rs5058 is associated with reduced blood pressure [27]. Most importantly, this study by Cannone et al [27] also reported that rs5058 Fig.…”

“…Recent studies from Olmsted County, Minnesota, confirm the studies of Newton-Cheh demonstrating that the ANP genetic variant rs5058 is associated with reduced blood pressure [27]. Most importantly, this study by Cannone et al [27] also reported that rs5058 Fig. 1 Biological actions and the metabolic and enzymatic clearance of atrial natriuretic peptide (ANP).…”

Natriuretic Peptides, Heart, and Adipose Tissue: New Findings and Future Developments for Diabetes Research

“…In the same cohort, the variant rs5068 within the ANP gene, which results in enhanced plasma ANP levels, was associated with a 12% reduced adjusted-risk of incident diabetes (61). Furthermore, other studies have reported that the rs5068 variant is associated with lower BMI, waist circumference, and prevalence of obesity and MetS (62,63).…”