Department of Clinical Sciences, Malmö University Hospital and Lund University, Malmö, Sweden.
PLoS One. 2007 May 9;2(5):e432. doi: 10.1371/journal.pone.0000432.
Neuronal precursor cell expressed developmentally down-regulated 4-like (NEDD4L) is a regulator of the amiloride-sensitive epithelial sodium channel (ENaC), thus a candidate gene for salt sensitivity. Carriers of an intact NEDD4L C2-domain, encoded by the NEDD4L rs4149601 (G/A) GG genotype, together with the C-allele of the NEDD4L rs2288774 (C/T) polymorphism have previously been shown to have increased blood pressure. Our aim was to test if genetic variation in NEDD4L is associated with increased salt sensitivity.
39 normotensive subjects were studied. The difference in 24-hour systolic blood pressure after four weeks on 150 mmol/day NaCl intake and four weeks on 50 mmol/day NaCl was defined as salt sensitivity. The rs4149601 and rs2288774 polymorphisms were genotyped using PCR-based techniques.
Carriers of the rs4149601 GG-genotype together with the rs2288774 CC-genotype had significantly higher salt sensitivity (median, IQR) (18.0, 7.5-20.0 mmHg vs 6.0, 0.0-10.0 mmHg, P = 0.007) and lower plasma renin concentration (P-renin) (6.0, 2.0-9.5 mU/L vs 15.0, 9.0-24.0 mU/L, P = 0.005) as compared to non-carriers of these genotypes. In carriers of the rs4149601 GG-genotype together with the rs2288774 CC- or CT-genotype, as compared to non-carriers, salt sensitivity was (8.0, 6.0-18.0 mmHg vs 5.0, 0.0-10.0 mmHg, P = 0.07) and P-renin (9.0, 6.0-16.0 mU/L vs 15.0, 9.0-28.0 mU/L, P = 0.03).
Genetic NEDD4L variation seems to affect salt sensitivity and P-renin in normotensive subjects, suggesting that genotyping of NEDD4L may be clinically useful in order to identify subjects who benefit from dietary salt restriction in the prevention of hypertension.
神经元前体细胞表达的发育下调 4 样蛋白（NEDD4L）是阿米洛利敏感的上皮钠通道（ENaC）的调节剂，因此是盐敏感性的候选基因。携带完整的 NEDD4L C2 结构域的个体，由 NEDD4L rs4149601（G/A）GG 基因型编码，以及 NEDD4L rs2288774（C/T）多态性的 C 等位基因，先前已显示出血压升高。我们的目的是测试 NEDD4L 的遗传变异是否与盐敏感性增加有关。
研究了 39 名血压正常的受试者。在摄入 150mmol/天氯化钠 4 周和摄入 50mmol/天氯化钠 4 周后 24 小时收缩压的差异被定义为盐敏感性。使用基于 PCR 的技术对 rs4149601 和 rs2288774 多态性进行基因分型。
携带 rs4149601 GG 基因型和 rs2288774 CC 基因型的个体盐敏感性明显升高（中位数，IQR）（18.0，7.5-20.0mmHg 比 6.0，0.0-10.0mmHg，P=0.007），血浆肾素浓度（P-肾素）降低（6.0，2.0-9.5mU/L 比 15.0，9.0-24.0mU/L，P=0.005）与这些基因型的非携带者相比。与 rs4149601 GG 基因型和 rs2288774 CC 或 CT 基因型的携带者相比，盐敏感性（8.0，6.0-18.0mmHg 比 5.0，0.0-10.0mmHg，P=0.07）和 P-肾素（9.0，6.0-16.0mU/L 比 15.0，9.0-28.0mU/L，P=0.03）也升高。
遗传 NEDD4L 变异似乎影响血压正常受试者的盐敏感性和 P-肾素，表明 NEDD4L 的基因分型可能在临床上有用，以确定从饮食盐限制中受益于高血压预防的受试者。
