A new mutation, R563Q, of the beta subunit of the epithelial sodium channel associated with low-renin, low-aldosterone hypertension
A new mutation, R563Q, of the beta subunit of the epithelial sodium channel associated with low-renin, low-aldosterone hypertension
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DOI：
10.1097/00004872-200305000-00016
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发表时间：
2003-05-01
影响因子：
4.9
通讯作者：
Davidson, JS
中科院分区：
文献类型：
--
作者：
Rayner, BL;Owen, EP;Davidson, JS
目的探讨肾上皮钠通道基因R563 Qa突变与高血压的关系。采用聚合酶链反应（PCR）扩增高血压患者和正常对照的上皮钠通道β亚基C-末端结构域的基因组DNA，用Sfc 1限制性内切酶消化筛选R563 Q突变，或测序。但在103名血压正常的黑人中均不存在，频率有显著性差异（P = 0.0058）。在黑人低肾素、低醛固酮高血压患者亚组（14例中有4例）中的突变频率显著（P = 0.0001）高于血压正常者，也高于（P = 0.041）正常-高肾素高血压患者，表明R563 Q是上皮钠通道的激活突变。在250例混合血统高血压患者中，有7例发现了R563 Q，并且在该人群中与低肾素、低醛固酮高血压显著相关（P = 0.017）。在100名混合血统血压正常者中发现了一个突变，但在136名白色高血压者中没有发现。在18例R563 Q患者中，11例有严重的高血压，导致肾功能衰竭的两例，而只有两个有低钾血症。结论R563 Q，一个新的变体β上皮钠通道，与低肾素，低醛固酮高血压，在南非黑人和混血儿患者。只有少数具有R563 Q等位基因的个体完全表达Liddle综合征表型。(C)2003年利平科特威廉姆斯威尔金斯。
Objective To determine the relationship between R563Q a mutation of the renal epithelial sodium channel, and hypertension.Methods Hypertensive patients with low renin and aldosterone, hypokalemia or resistant hypertension were selected for DNA analysis. Genomic DNA encoding the C-terminal domain of the epithelial sodium channel beta subunit from hypertensives and controls was amplified by polymerase chain reaction and screened for the R563Q mutation by digestion with Sfc1 restriction enzyme, or sequenced.Results A previously undescribed mutation, R5630, of the beta epithelial sodium channel was found in 10 of 139 black hypertensives, but was not present in any of 103 black normotensives, a significant (P = 0.0058) difference in frequency. The frequency of the mutation in the subgroup of black low-renin, low-aldosterone hypertensives (four of 14) was significantly (P = 0.0001) greater than in normotensives, and was also greater (P = 0.041) than in normal-high renin hypertensives, suggesting that R563Q is an activating mutation of the epithelial sodium channel. R563Q was also found in seven out of 250 mixed ancestry hypertensives, and was significantly (P = 0.017) associated with low-renin, low-aldosterone hypertension in this population group. The mutation was found in one of 100 mixed ancestry normotensives but not in any of 136 white hypertensives. Of the 18 R563Q patients, 11 had severe hypertension, leading to renal failure in two cases, while only two had hypokalaemia.Conclusions R563Q, a new variant of the beta epithelial sodium channel, is associated with low-renin, low-aldosterone hypertension, in South African black and mixed-ancestry patients. Only a minority of individuals with the R563Q allelle fully express the Liddle's syndrome phenotype. (C) 2003 Lippincott Williams Wilkins.