促肾上腺皮质激素与类固醇生成位点多态性作为醛固酮分泌和血压的决定因素
ACTH and Polymorphisms at Steroidogenic Loci as Determinants of Aldosterone Secretion and Blood Pressure.
作者信息
MacKenzie Scott M, Freel E Marie, Connell John M, Fraser Robert, Davies Eleanor
机构信息
Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK.
Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK.
出版信息
Int J Mol Sci. 2017 Mar 7;18(3):579. doi: 10.3390/ijms18030579.
The majority of genes contributing to the heritable component of blood pressure remain unidentified, but there is substantial evidence to suggest that common polymorphisms at loci involved in the biosynthesis of the corticosteroids aldosterone and cortisol are important. This view is supported by data from genome-wide association studies that consistently link the CYP17A1 locus to blood pressure. In this review article, we describe common polymorphisms at three steroidogenic loci (CYP11B2, CYP11B1 and CYP17A1) that alter gene transcription efficiency and levels of key steroids, including aldosterone. However, the mechanism by which this occurs remains unclear. While the renin angiotensin system is rightly regarded as the major driver of aldosterone secretion, there is increasing evidence that the contribution of corticotropin (ACTH) is also significant. In light of this, we propose that the differential response of variant CYP11B2, CYP11B1 and CYP17A1 genes to ACTH is an important determinant of blood pressure, tending to predispose individuals with an unfavourable genotype to hypertension.
大多数对血压遗传成分有影响的基因仍未被识别，但有大量证据表明，参与皮质类固醇醛固酮和皮质醇生物合成的基因座上的常见多态性很重要。全基因组关联研究的数据支持了这一观点，这些数据一致将CYP17A1基因座与血压联系起来。在这篇综述文章中，我们描述了三个类固醇生成基因座（CYP11B2、CYP11B1和CYP17A1）上的常见多态性，这些多态性会改变基因转录效率和关键类固醇（包括醛固酮）的水平。然而，其发生机制仍不清楚。虽然肾素血管紧张素系统被公认为醛固酮分泌的主要驱动因素，但越来越多的证据表明促肾上腺皮质激素（ACTH）的作用也很显著。有鉴于此，我们提出，变异的CYP11B2、CYP11B1和CYP17A1基因对ACTH的不同反应是血压的一个重要决定因素，倾向于使具有不利基因型的个体易患高血压。
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