aDepartment of Clinical Sciences in Malmö, Lund University bDepartment of Internal Medicine, Skåne University Hospital, Malmö, Sweden.
J Hypertens. 2014 Feb;32(2):294-9. doi: 10.1097/HJH.0000000000000044.
We have previously shown that genetic variance in NEDD4L, a regulating protein of a sodium channel in the distal nephron, has been associated with marginally higher blood pressure and enhanced salt sensitivity. Here, we tested if the genetic NEDD4L variation previously associated with salt sensitivity is related to population blood pressure, incidence of cardiovascular disease (CVD) and mortality.
We genotyped the rs4149601 A→G and rs2288774 T→C NEDD4L variants in 27,564 participants of the Malmö Diet and Cancer Study. The genotype combination previously shown to be associated with salt sensitivity (rs4149601 GG+rs2288774 CC), which was present in 9.6% of participants, was related to cross sectional blood pressure as well as to CVD incidence and mortality during a median follow-up time of 14 years using Cox regression models.
Carriers of the NEDD4L salt sensitivity-associated genotype had (mean ± SEM) higher systolic (142 ± 0.4 vs. 141 ± 0.1 mmHg, P = 0.002) and diastolic (86.0 ± 0.5 vs. 85.6 ± 0.2 mmHg, P = 0.025) blood pressure and multivariate adjusted hazards ratio (95% confidence interval) of CVD 1.13 (1.02-1.25, P = 0.018), coronary events 1.20 (1.06-1.37; P = 0.005) and cardiovascular mortality 1.17 (0.99-1.37; P = 0.055) than noncarriers but there was no significant difference in the incidence of stroke and total mortality.
The NEDD4L salt sensitivity-associated genotype was associated with higher blood pressure, which may translate into increased risk for CVD morbidity and mortality. Interestingly, there was no association with stroke suggesting that the association is partially blood pressure independent.
我们之前已经表明，远端肾单位钠通道调节蛋白 NEDD4L 的遗传变异与血压略有升高和盐敏感性增强有关。在这里，我们测试了先前与盐敏感性相关的遗传 NEDD4L 变异是否与人群血压、心血管疾病（CVD）发病率和死亡率有关。
我们在马尔默饮食与癌症研究的 27564 名参与者中检测了 NEDD4L 的 rs4149601 A→G 和 rs2288774 T→C 基因变异。以前与盐敏感性相关的基因型组合（rs4149601 GG+rs2288774 CC）在 9.6%的参与者中存在，使用 Cox 回归模型，该基因型组合与横断面血压以及 14 年的中位随访期间的 CVD 发病率和死亡率有关。
携带 NEDD4L 盐敏感性相关基因型的患者（平均值±SEM）的收缩压（142±0.4 vs. 141±0.1 mmHg，P=0.002）和舒张压（86.0±0.5 vs. 85.6±0.2 mmHg，P=0.025）更高，多变量调整后的 CVD 危险比（95%置信区间）为 1.13（1.02-1.25，P=0.018）、冠心病事件 1.20（1.06-1.37；P=0.005）和心血管死亡率 1.17（0.99-1.37；P=0.055）高于非携带者，但卒中发病率和总死亡率无显著差异。
NEDD4L 盐敏感性相关基因型与较高的血压有关，这可能转化为 CVD 发病率和死亡率增加的风险。有趣的是，与卒中没有关联，这表明这种关联部分是独立于血压的。
