TY - JOUR
T1 - An NPPB promoter polymorphism associated with elevated N-terminal pro-b-type natriuretic peptide and lower blood pressure, hypertension, and mortality
AU - Seidelmann, Sara B.
AU - Vardeny, Orly
AU - Claggett, Brian
AU - Yu, Bing
AU - Shah, Amil M.
AU - Ballantyne, Christie M.
AU - Selvin, Elizabeth
AU - MacRae, Calum A.
AU - Boerwinkle, Eric
AU - Solomon, Scott D.
N1 - Publisher Copyright:
© 2017 The Authors.
PY - 2017/4/1
Y1 - 2017/4/1
N2 - Background-Elevated B-type natriuretic peptide (BNP) levels are associated with heart failure and increased mortality in the general population. We investigated rs198389, a functional variant in the promoter region of the BNP gene (NPPB), in patients from the Atherosclerosis Risk in Communities Study to investigate associations with N-terminal pro-BNP (NT-proBNP) levels and outcomes. Methods and Results-A total of 11 361 black and white patients with rs198389 genotyping attended visit 1 (aged 45-64 years; 1987-1989), with follow-up visits occurring every 3 years (visit 2-visit 4, 1990-1999), followed by visit 5 (2011-2013). NTproBNP levels were measured at visits 2, 4, and 5. At visit 2, the GG genotype (frequency 18%) was associated with a 41% higher mean plasma level of NT-proBNP compared with the AA genotype (frequency 34%), with intermediate values observed in AGs (P = 4.2×10-52). The GG genotype was associated with reduced systolic blood pressure (-1.6 mm Hg, P=0.006), diastolic blood pressure (-1 mm Hg, P = 0.003), antihypertension medication use (odds ratio, 0.85; 95% CI, 0.74-0.97 [P = 0.02]), and hypertension (odds ratio, 0.81; 95% CI, 0.72-0.92 [P = 0.002]) compared with the AA genotype with intermediate values in AGs. These relationships persisted throughout subsequent visits. After a median follow-up of 23 years, there were 4031 deaths. With and without covariate adjustment, the GG genotype was associated with modestly lower mortality (hazard ratio, 0.86; 95% CI, 0.78-0.95), primarily reflective of cardiovascular death (hazard ratio, 0.75; 95% CI, 0.61-0.92), and increased residual lifespan of 8 months from 50 years of age (P=0.02) versus AAs. Conclusions-The rs198389 G allele in the NPPB promoter is associated with elevated levels of NT-proBNP throughout adult life, reduced blood pressure, hypertension and cardiovascular mortality, and increased lifespan.
AB - Background-Elevated B-type natriuretic peptide (BNP) levels are associated with heart failure and increased mortality in the general population. We investigated rs198389, a functional variant in the promoter region of the BNP gene (NPPB), in patients from the Atherosclerosis Risk in Communities Study to investigate associations with N-terminal pro-BNP (NT-proBNP) levels and outcomes. Methods and Results-A total of 11 361 black and white patients with rs198389 genotyping attended visit 1 (aged 45-64 years; 1987-1989), with follow-up visits occurring every 3 years (visit 2-visit 4, 1990-1999), followed by visit 5 (2011-2013). NTproBNP levels were measured at visits 2, 4, and 5. At visit 2, the GG genotype (frequency 18%) was associated with a 41% higher mean plasma level of NT-proBNP compared with the AA genotype (frequency 34%), with intermediate values observed in AGs (P = 4.2×10-52). The GG genotype was associated with reduced systolic blood pressure (-1.6 mm Hg, P=0.006), diastolic blood pressure (-1 mm Hg, P = 0.003), antihypertension medication use (odds ratio, 0.85; 95% CI, 0.74-0.97 [P = 0.02]), and hypertension (odds ratio, 0.81; 95% CI, 0.72-0.92 [P = 0.002]) compared with the AA genotype with intermediate values in AGs. These relationships persisted throughout subsequent visits. After a median follow-up of 23 years, there were 4031 deaths. With and without covariate adjustment, the GG genotype was associated with modestly lower mortality (hazard ratio, 0.86; 95% CI, 0.78-0.95), primarily reflective of cardiovascular death (hazard ratio, 0.75; 95% CI, 0.61-0.92), and increased residual lifespan of 8 months from 50 years of age (P=0.02) versus AAs. Conclusions-The rs198389 G allele in the NPPB promoter is associated with elevated levels of NT-proBNP throughout adult life, reduced blood pressure, hypertension and cardiovascular mortality, and increased lifespan.
KW - Blood pressure
KW - Hypertension
KW - Mortality
KW - N-terminal pro-B-type
KW - NPPB
KW - Natriuretic peptide
KW - Polymorphism
KW - Rs198389
KW - Single nucleotide polymorphism
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U2 - 10.1161/JAHA.116.005257
DO - 10.1161/JAHA.116.005257
M3 - Article
C2 - 28341776
AN - SCOPUS:85016572878
SN - 2047-9980
VL - 6
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 4
M1 - e005257
ER -