An NPPB promoter polymorphism associated with elevated N-terminal pro-b-type natriuretic peptide and lower blood pressure, hypertension, and mortality

Sara B. Seidelmann, Orly Vardeny, Brian Claggett, Bing Yu, Amil M. Shah, Christie M. Ballantyne, Elizabeth Selvin, Calum A. MacRae, Eric Boerwinkle, Scott D. Solomon

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


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.

Original languageEnglish (US)
Article numbere005257
JournalJournal of the American Heart Association
Issue number4
StatePublished - Apr 1 2017
Externally publishedYes

Bibliographical note

Funding Information:
The authors thank the staff and participants of the ARIC study for their important contributions. The ARIC study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268 201100009C, HHSN268201100010C, HHSN2682011 00011C, and HHSN268201100012C). Dr Seidelmann is supported by National Institutes of Health grant number 2T32HL094301-06.

Publisher Copyright:
© 2017 The Authors.


  • Blood pressure
  • Hypertension
  • Mortality
  • N-terminal pro-B-type
  • NPPB
  • Natriuretic peptide
  • Polymorphism
  • Rs198389
  • Single nucleotide polymorphism

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