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
Cardiovascular Division, Brigham and Women's Hospital, Boston, MA.
Division of Cardiovascular Imaging, Department of Radiology, Brigham and Women's Hospital, Boston, MA.
J Am Heart Assoc. 2017 Mar 24;6(4):e005257. doi: 10.1161/JAHA.116.005257.
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 (), in patients from the Atherosclerosis Risk in Communities Study to investigate associations with N-terminal pro-BNP (NT-proBNP) levels and outcomes.
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 (=4.2×10). The GG genotype was associated with reduced systolic blood pressure (-1.6 mm Hg, =0.006), diastolic blood pressure (-1 mm Hg, =0.003), antihypertension medication use (odds ratio, 0.85; 95% CI, 0.74-0.97 [=0.02]), and hypertension (odds ratio, 0.81; 95% CI, 0.72-0.92 [=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 (=0.02) versus AAs.
The rs198389 G allele in the promoter is associated with elevated levels of NT-proBNP throughout adult life, reduced blood pressure, hypertension and cardiovascular mortality, and increased lifespan.
在普通人群中，B型利钠肽（BNP）水平升高与心力衰竭及死亡率增加相关。我们在社区动脉粥样硬化风险研究的患者中，对BNP基因启动子区域的一个功能性变异rs198389进行了研究，以探讨其与N末端前脑钠肽（NT-proBNP）水平及预后的关联。
共有11361名进行了rs198389基因分型的黑人和白人患者参加了第1次随访（年龄45 - 64岁；1987 - 1989年），随后每3年进行一次随访（第2 - 4次随访，1990 - 1999年），接着是第5次随访（2011 - 2013年）。在第2、4和5次随访时测量NT-proBNP水平。在第2次随访时，与AA基因型（频率34%）相比，GG基因型（频率18%）的NT-proBNP平均血浆水平高41%，AG基因型的值介于两者之间（=4.2×10）。与AA基因型相比，GG基因型与收缩压降低（-1.6 mmHg，=0.006）、舒张压降低（-1 mmHg，=0.003）、抗高血压药物使用减少（比值比，0.85；95%可信区间，0.74 - 0.97 [=0.02]）以及高血压患病率降低（比值比，0.81；95%可信区间，0.72 - 0.92 [=0.002]）相关，AG基因型的值介于两者之间。这些关系在随后的随访中持续存在。经过23年的中位随访，有4031人死亡。无论是否进行协变量调整，GG基因型与死亡率略有降低相关（风险比，0.86；95%可信区间，0.78 - 0.95），主要反映在心血管死亡方面（风险比，0.75；95%可信区间，0.61 - 0.92），并且与AA基因型相比，50岁时剩余寿命增加8个月（=0.02）。
BNP基因启动子区域的rs198389 G等位基因与成年期NT-proBNP水平升高、血压降低、高血压及心血管死亡率降低以及寿命延长相关。
