Polymorphism in NEDD4L is associated with increased salt sensitivity, reduced levels of P-renin and increased levels of Nt-proANP.
Polymorphism in NEDD4L is associated with increased salt sensitivity, reduced levels of P-renin and increased levels of Nt-proANP.
复制标题
NEDD4L中的多态性与盐敏感性升高，P-肾脏水平降低以及NT-ProANP水平增加有关。
DOI：
10.1371/journal.pone.0000432
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发表时间：
2007-05-09
期刊：
影响因子：
3.7
通讯作者：
Melander, Olle
中科院分区：
文献类型：
--
作者：
Dahlberg, Jonas;Nilsson, Lars-Olof;von Wowern, Fredrik;Melander, Olle
神经元前体细胞表达的发育下调 4 样蛋白 (NEDD4L) 是阿米洛利敏感上皮钠通道 (ENaC) 的调节因子，因此是盐敏感性的候选基因。由 NEDD4L rs4149601 (G/A) GG 基因型编码的完整 NEDD4L C2 结构域的携带者，以及 NEDD4L rs2288774 (C/T) 多态性的 C 等位基因，先前已被证明会导致血压升高。我们的目的是测试 NEDD4L 的遗传变异是否与盐敏感性增加相关。对 39 名血压正常的受试者进行了研究。摄入 150 mmol/天 NaCl 4 周后和摄入 50 mmol/天 NaCl 4 周后 24 小时收缩压的差异定义为盐敏感性。使用基于PCR的技术对rs4149601和rs2288774多态性进行基因分型。 rs4149601 GG 基因型和 rs2288774 CC 基因型的携带者具有显着更高的盐敏感性（中位数，IQR）（18.0, 7.5–20.0 mmHg vs 6.0, 0.0–10.0 mmHg, P = 0.007）和较低的血浆肾素浓度（P-renin） (6.0, 2.0–9.5 mU/L vs 15.0, 9.0–24.0 mU/L, P = 0.005) 与这些基因型的非携带者相比。在 rs4149601 GG 基因型以及 rs2288774 CC 或 CT 基因型的携带者中，与非携带者相比，盐敏感性为（8.0, 6.0–18.0 mmHg vs 5.0, 0.0–10.0 mmHg, P = 0.07）和 P-肾素（9.0, 6.0–16.0 mU/L 对比 15.0, 9.0–28.0 mU/L, P = 0.03)。遗传性 NEDD4L 变异似乎会影响血压正常受试者的盐敏感性和 P-肾素，这表明 NEDD4L 的基因分型可能在临床上有用，以确定哪些受试者受益于饮食盐限制以预防高血压。
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.
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