|Title||An NPPB Promoter Polymorphism Associated With Elevated N-Terminal pro-B-Type Natriuretic Peptide and Lower Blood Pressure, Hypertension, and Mortality.|
|Publication Type||Journal Article|
|Year of Publication||2017|
|Authors||Seidelmann, SB, Vardeny, O, Claggett, B, Yu, B, Shah, AM, Ballantyne, CM, Selvin, E, MacRae, CA, Boerwinkle, E, Solomon, SD|
|Journal||J Am Heart Assoc|
|Date Published||2017 Mar 24|
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.
|Alternate Journal||J Am Heart Assoc|
|PubMed Central ID||PMC5533018|
|Grant List||K24 DK106414 / DK / NIDDK NIH HHS / United States |
R01 DK089174 / DK / NIDDK NIH HHS / United States
R24 OD017870 / OD / NIH HHS / United States