Kidney ion handling genes and their interaction in blood pressure control.
Kidney ion handling genes and their interaction in blood pressure control.
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DOI：
10.1042/bsr20220977
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发表时间：
2022-11-30
影响因子：
4
通讯作者：
中科院分区：
文献类型：
--
作者：
高血压影响30%的成年人，是心血管疾病的主要危险因素。肾钠重吸收在原发性高血压的发病和发展过程中起着至关重要的作用。肾脏离子处理基因的变异与血压和高血压的临床特征有关，这已经被广泛报道。然而，这些变异改变蛋白质功能的潜在机制很少被总结。此外，单个基因的变异往往局限于对血压的显著影响。在过去的几十年里，基因×基因（G × G）和/或基因型×环境（G × E）相互作用对特定性状（如血压）的影响已被广泛考虑，特别是在多基因遗传性状的研究中。本文综述了肾离子处理基因的遗传学研究进展，分别编码Na+通道（Na+-Cl−共转运体[NCC]、Na-K- 2cl共转运体[NKCC2]、上皮Na+通道[ENaCs]）、K+通道（肾外髓钾通道[ROMK]）和Cl−通道（Pendrin、氯离子电压门控通道Kb [CLC-Kb]）及其上游激酶WNKs和SGK1。我们试图阐明这些基因是如何参与肾脏钠吸收和影响血压的，特别是强调遗传变异改变蛋白质功能和相互作用在血压调节中的潜在机制。本文旨在加深我们对肾离子处理基因/通道在血压控制中的重要作用的认识。
Hypertension affects 30% of adults and is the leading risk factor for cardiovascular disease. Kidney sodium reabsorption plays a vital role in the initial stage and development of essential hypertension. It has been extensively reported that the variants of kidney ion handling genes are associated to blood pressure, and clinical features of hypertension. However, the underlying mechanisms by which these variants alter protein function are rarely summarized. In addition, the variation of one single gene is often limited to induce a significant effect on blood pressure. In the past few decades, the influence by genes × genes (G × G) and/or genotype × environment (G × E) interactions on a given trait, for example, blood pressure, have been widely considered, especially in studies on polygenic genetic traits. In the present review, we discuss the progress in genetics studies on kidney ion handling genes, encoding Na+ channels (Na+-Cl− cotransporter [NCC], Na-K-2Cl cotransporter [NKCC2], epithelial Na+ channels [ENaCs]), K+ channel (renal outer medullary potassium channel [ROMK]), and Cl− channels (Pendrin, chloride voltage-gated channel Kb [CLC-Kb]), respectively, and their upstream kinases, WNKs and SGK1. We seek to clarify how these genes are involved in kidney sodium absorption and influence blood pressure, especially emphasizing the underlying mechanisms by which genetic variants alter protein functions and interaction in blood pressure regulation. The present review aims to enhance our understanding of the important role of kidney ion handling genes/channels in blood pressure control.
影响因子：
3.7
作者：
Li C;Yang X;He J;Hixson JE;Gu D;Rao DC;Shimmin LC;Huang J;Gu CC;Chen J;Li J;Kelly TN
通讯作者：
Kelly TN