Rare mutations in renal sodium and potassium transporter genes exhibit impaired transport function.

Rare mutations in renal sodium and potassium transporter genes exhibit impaired transport function.
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DOI:
10.1097/01.mnh.0000437204.84826.99
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发表时间:
2014-01
影响因子:
3.2
通讯作者:
Welling PA
Welling PA
中科院分区:
医学3区
文献类型:
--
作者:
Welling PA

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最近探索高血压遗传基础的努力表明,肾脏盐转运基因的罕见突变会导致普通人群的血压变化和高血压易感性。当前的综述重点关注这些最新发现,重点讨论罕见突变及其如何影响运输功能。赋予低血压特征和抗高血压能力的罕见突变最近得到了广泛研究。对受影响的肾盐转运分子(NKCC2 (SLC12A1)、ROMK (KCNJ1) 和 NCC (SLC12A3))的生理和生化分析表明,大多数突变实际上会导致转运功能丧失。这些突变通过许多不同的机制破坏运输,包括改变生物合成加工、运输、离子运输和调节。最近出现了对高血压遗传基础的新见解,支持罕见而非常见基因变异的主要作用。已发现许多不同的罕见突变通过不同的机制影响不同盐转运蛋白基因的功能,但都赋予相同的血压表型。这些研究强化了肾脏和肾脏盐转运在血压调节和高血压中的关键作用。
Recent efforts to explore the genetic underpinnings of hypertension revealed rare mutations in kidney salt transport genes contribute to blood pressure variation and hypertension susceptibility in the general population. The current review focuses on these latest findings, highlighting a discussion about the rare mutations and how they affect transport function. Rare mutations that confer a low blood pressure trait and resistance to hypertension have recently been extensively studied. Physiological and biochemical analyses of the effected renal salt transport molecules (NKCC2 (SLC12A1), ROMK (KCNJ1), and NCC (SLC12A3)) revealed that most of the mutations do, in fact, cause a loss of transport function. The mutations disrupt transport by many different mechanisms, including altering biosynthetic processing, trafficking, ion transport, and regulation. New insights into the genetic basis of hypertension have recently emerged, supporting a major role of rare, rather than common, gene variants. Many different rare mutations have been found to affect the functions of different salt transporter genes by different mechanisms, yet all confer the same blood pressure phenotype. These studies reinforce the critical roles of the kidney, and renal salt transport in blood pressure regulation and hypertension.
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影响因子: 64.8
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