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

作者：Seidelmann Sara B; Vardeny Orly; Claggett Brian; Yu Bing; Shah Amil M; Ballantyne Christie M; Selvin Elizabeth; MacRae Calum A; Boerwinkle Eric; Solomon Scott D^*

来源：Journal of the American Heart Association, 2017, 6(4): e005257.

DOI：10.1161/JAHA.116.005257

• blood pressure
• hypertension
• mortality
• natriuretic peptide
• NPPB
• N-terminal pro-B-type
• polymorphism
• rs198389
• single nucleotide polymorphism

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 rs 198389 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 x10(-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% Cl, 0.74-0.97 [P=0.02]), and hypertension (odds ratio, 0.81; 95% Cl, 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% Cl, 0.78-0.95), primarily reflective of cardiovascular death (hazard ratio, 0.75; 95% Cl, 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.

• 出版日期2017-4