TY - JOUR
T1 - Atrial natriuretic peptide genetic variant rs5065 and risk for cardiovascular disease in the general community
T2 - A 9-year follow-up study
AU - Cannone, Valentina
AU - Huntley, Brenda K.
AU - Olson, Timothy M.
AU - Heublein, Denise M.
AU - Scott, Christopher G.
AU - Bailey, Kent R.
AU - Redfield, Margaret M.
AU - Rodeheffer, Richard J.
AU - Burnett, John C.
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013/11
Y1 - 2013/11
N2 - We analyzed the phenotype associated with the atrial natriuretic peptide (ANP) genetic variant rs5065 in a random community-based sample. We also assessed and compared the biological action of 2 concentrations (10 mol/L, 10 mol/L) of ANP and ANP-RR, the protein variant encoded by the minor allele of rs5065, on activation of the guanylyl cyclase (GC)-A and GC-B receptors, production of the second messenger 3′,5′-cGMP in endothelial cells, and endothelial permeability. rs5065 genotypes were determined in a cross-sectional adult cohort from Olmsted County, MN (n=1623). Genotype frequencies for rs5065 were 75%, 24%, and 1% for TT, TC, and CC, respectively. Multivariate analysis showed that the C allele was associated with increased risk of cerebrovascular accident (hazard ratio, 1.43; 95% confidence interval, 1.09-1.86; P=0.009) and higher prevalence of myocardial infarction (odds ratio, 1.82; 95% confidence interval, 1.07-3.09; P=0.026). ANP-RR 10 mol/L activated the GC-A receptor (83.07±8.31 versus no treatment 0.18±0.04 per 6 wells; P=0.006), whereas ANP-RR 10 mol/L did not. Neither 10 mol/L nor 10 mol/L ANP-RR activated GC-B receptor (P=0.10, P=0.35). ANP 10 mol/L and ANP-RR 10 mol/L stimulated 3′,5′-cGMP production in endothelial cells similarly (P=0.58). Both concentrations of ANP-RR significantly enhanced human aortic endothelial cell permeability (69 versus 29 relative fluorescence units [RFUs], P=0.012; 58 versus 39 RFUs, P=0.015) compared with ANP. The minor allele of rs5065 was associated with increased cardiovascular risk. ANP-RR activated the GC-A receptor, increased 3′,5′-cGMP in endothelial cells, and when compared with ANP, augmented endothelial cell permeability.
AB - We analyzed the phenotype associated with the atrial natriuretic peptide (ANP) genetic variant rs5065 in a random community-based sample. We also assessed and compared the biological action of 2 concentrations (10 mol/L, 10 mol/L) of ANP and ANP-RR, the protein variant encoded by the minor allele of rs5065, on activation of the guanylyl cyclase (GC)-A and GC-B receptors, production of the second messenger 3′,5′-cGMP in endothelial cells, and endothelial permeability. rs5065 genotypes were determined in a cross-sectional adult cohort from Olmsted County, MN (n=1623). Genotype frequencies for rs5065 were 75%, 24%, and 1% for TT, TC, and CC, respectively. Multivariate analysis showed that the C allele was associated with increased risk of cerebrovascular accident (hazard ratio, 1.43; 95% confidence interval, 1.09-1.86; P=0.009) and higher prevalence of myocardial infarction (odds ratio, 1.82; 95% confidence interval, 1.07-3.09; P=0.026). ANP-RR 10 mol/L activated the GC-A receptor (83.07±8.31 versus no treatment 0.18±0.04 per 6 wells; P=0.006), whereas ANP-RR 10 mol/L did not. Neither 10 mol/L nor 10 mol/L ANP-RR activated GC-B receptor (P=0.10, P=0.35). ANP 10 mol/L and ANP-RR 10 mol/L stimulated 3′,5′-cGMP production in endothelial cells similarly (P=0.58). Both concentrations of ANP-RR significantly enhanced human aortic endothelial cell permeability (69 versus 29 relative fluorescence units [RFUs], P=0.012; 58 versus 39 RFUs, P=0.015) compared with ANP. The minor allele of rs5065 was associated with increased cardiovascular risk. ANP-RR activated the GC-A receptor, increased 3′,5′-cGMP in endothelial cells, and when compared with ANP, augmented endothelial cell permeability.
KW - atrial natriuretic peptides
KW - cardiovascular diseases
KW - natriuretic peptidesstroke
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UR - http://www.scopus.com/inward/citedby.url?scp=84886412379&partnerID=8YFLogxK
U2 - 10.1161/HYPERTENSIONAHA.113.01344
DO - 10.1161/HYPERTENSIONAHA.113.01344
M3 - Article
C2 - 24041948
AN - SCOPUS:84886412379
SN - 0194-911X
VL - 62
SP - 860
EP - 865
JO - Hypertension
JF - Hypertension
IS - 5
ER -