title: A genetic variant of the atrial natriuretic peptide gene is associated with cardiometabolic protection in the general community.
abstract: OBJECTIVE
  We sought to define the cardiometabolic phenotype associated with rs5068, a genetic variant of the atrial natriuretic peptide (ANP) gene.
  
  
  BACKGROUND
  The ANP and B-type natriuretic peptide play an important role in cardiorenal homeostasis but also exert metabolic actions.
  
  
  METHODS
  We genotyped 1,608 randomly selected residents from Olmsted County, Minnesota. Subjects were well-characterized.
  
  
  RESULTS
  Genotype frequencies were: AA 89.9%, AG 9.7%, and GG 0.4%; all subsequent analyses were AA versus AG+GG. The G allele was associated with increased plasma levels of N-terminal pro-atrial natriuretic peptide (p = 0.002), after adjustment for age and sex. The minor allele was also associated with lower body mass index (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 high-density lipoprotein 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). The associations between the G allele and high-density lipoprotein cholesterol, C-reactive protein values, myocardial infarction, and metabolic syndrome were not significant, after adjusting for BMI; the associations with systolic blood pressure, BMI, obesity, and waist circumference remained significant even after adjusting for N-terminal pro-atrial natriuretic peptide.
  
  
  CONCLUSIONS
  In a random sample of the general U.S. population, the minor allele of rs5068 is associated with a favorable cardiometabolic profile. These findings suggest that rs5068 or genetic loci in linkage disequilibrium might 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.
authors.affiliation: Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic and Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA. cannone.valentina@mayo.edu
authors.forename: Valentina
authors.initials: V
authors.lastname: Cannone
authors.forename: Guido
authors.initials: G
authors.lastname: Boerrigter
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cataliotti
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Costello-Boerrigter
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Olson
authors.forename: Paul M
authors.initials: PM
authors.lastname: McKie
authors.forename: Denise M
authors.initials: DM
authors.lastname: Heublein
authors.forename: Brian D
authors.initials: BD
authors.lastname: Lahr
authors.forename: Kent R
authors.initials: KR
authors.lastname: Bailey
authors.forename: Maurizio
authors.initials: M
authors.lastname: Averna
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Redfield
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Rodeheffer
authors.forename: John C
authors.initials: JC
authors.lastname: Burnett
mesh_terms: D000368:Aged; D000483:Alleles; D009320:Atrial Natriuretic Factor / Q000235:genetics*; D001794:Blood Pressure; D015992:Body Mass Index; D004247:DNA / Q000378:metabolism; D015150:Echocardiography, Doppler / Q000379:methods; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006706:Homeostasis; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000235:genetics; D010641:Phenotype; D017434:Protein Structure, Tertiary; D011897:Random Allocation
chemical_list: D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D004247:DNA