Format

Send to

Choose Destination
J Am Heart Assoc. 2017 Mar 24;6(4). pii: e005257. doi: 10.1161/JAHA.116.005257.

An NPPB Promoter Polymorphism Associated With Elevated N-Terminal pro-B-Type Natriuretic Peptide and Lower Blood Pressure, Hypertension, and Mortality.

Author information

1
Cardiovascular Division, Brigham and Women's Hospital, Boston, MA.
2
Division of Cardiovascular Imaging, Department of Radiology, Brigham and Women's Hospital, Boston, MA.
3
Departments of Pharmacy and Medicine, University of Wisconsin-Madison, Madison, WI.
4
Epidemiology, Human Genetics & Environmental Sciences, UTHealth School of Public Health, Houston, TX.
5
Methodist DeBakey Heart Center, Baylor College of Medicine, Houston, TX.
6
The Johns Hopkins Institute for Clinical and Translational Research, Baltimore, MD.
7
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX.
8
Cardiovascular Division, Brigham and Women's Hospital, Boston, MA ssolomon@bwh.harvard.edu.

Abstract

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). NT-proBNP 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.

KEYWORDS:

NPPB ; N‐terminal pro–B‐type; blood pressure; hypertension; mortality; natriuretic peptide; polymorphism; rs198389; single nucleotide polymorphism

PMID:
28341776
PMCID:
PMC5533018
DOI:
10.1161/JAHA.116.005257
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center