A genetic variant of the atrial natriuretic peptide gene is associated with cardiometabolic protection in the general community

Valentina Cannone, Guido Boerrigter, Alessandro Cataliotti, Lisa C. Costello-Boerrigter, Timothy Mark Olson, Paul McKie, Denise M. Heublein, Brian D. Lahr, Kent R Bailey, Maurizio Averna, Margaret May Redfield, Richard J. Rodeheffer, John C Jr. Burnett

Research output: Contribution to journalArticle

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Abstract

Objectives: 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.

Original languageEnglish (US)
Pages (from-to)629-636
Number of pages8
JournalJournal of the American College of Cardiology
Volume58
Issue number6
DOIs
StatePublished - Aug 2 2011

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Atrial Natriuretic Factor
Alleles
Blood Pressure
Body Mass Index
Genes
Waist Circumference
C-Reactive Protein
HDL Cholesterol
Obesity
Myocardial Infarction
Natriuretic Peptides
Genetic Loci
Brain Natriuretic Peptide
Disease Susceptibility
Linkage Disequilibrium
Homeostasis
Genotype
Phenotype
Population

Keywords

  • atrial natriuretic peptide
  • cardiometabolic disease
  • lipid metabolism
  • metabolic syndrome
  • natriuretic peptides

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

A genetic variant of the atrial natriuretic peptide gene is associated with cardiometabolic protection in the general community. / Cannone, Valentina; Boerrigter, Guido; Cataliotti, Alessandro; Costello-Boerrigter, Lisa C.; Olson, Timothy Mark; McKie, Paul; Heublein, Denise M.; Lahr, Brian D.; Bailey, Kent R; Averna, Maurizio; Redfield, Margaret May; Rodeheffer, Richard J.; Burnett, John C Jr.

In: Journal of the American College of Cardiology, Vol. 58, No. 6, 02.08.2011, p. 629-636.

Research output: Contribution to journalArticle

Cannone, Valentina ; Boerrigter, Guido ; Cataliotti, Alessandro ; Costello-Boerrigter, Lisa C. ; Olson, Timothy Mark ; McKie, Paul ; Heublein, Denise M. ; Lahr, Brian D. ; Bailey, Kent R ; Averna, Maurizio ; Redfield, Margaret May ; Rodeheffer, Richard J. ; Burnett, John C Jr. / A genetic variant of the atrial natriuretic peptide gene is associated with cardiometabolic protection in the general community. In: Journal of the American College of Cardiology. 2011 ; Vol. 58, No. 6. pp. 629-636.
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abstract = "Objectives: 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.",
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AU - Cannone, Valentina

AU - Boerrigter, Guido

AU - Cataliotti, Alessandro

AU - Costello-Boerrigter, Lisa C.

AU - Olson, Timothy Mark

AU - McKie, Paul

AU - Heublein, Denise M.

AU - Lahr, Brian D.

AU - Bailey, Kent R

AU - Averna, Maurizio

AU - Redfield, Margaret May

AU - Rodeheffer, Richard J.

AU - Burnett, John C Jr.

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N2 - Objectives: 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.

AB - Objectives: 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.

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