Luft F C, Schuster H, Bilginturan N, Wienker T
Franz Volhard Clinic, Max Delbruck Centre for Molecular Medicine, Virchow Klinikum, Humboldt University of Berlin, Germany.
J Hypertens. 1995 Dec;13(12 Pt 2):1535-8.
To discuss the relevance of rare monogenic forms of hypertension to the diagnosis, pathogenesis and treatment of essential hypertension.
Three monogenic forms of hypertension have been identified that are inherited as a simple autosomal-dominant trait. The genetic defects and the pathophysiology of two, namely glucocorticoid-remediable aldosteronism and Liddle's syndrome, have been elucidated in great detail. The third form of monogenic hypertension, which cosegregates with a second phenotype, brachydactyly, is being investigated.
Glucocorticoid-remediable aldosteronism is caused by the presence of a chimeric gene, which incorporates the regulatory region of the 11-beta-hydroxylase gene and the structural portion of the aldosterone synthase gene. The enzyme aldosterone synthase is not only expressed in the zona fasiculata but is also regulated by adrenocorticotrophic hormone in this condition. Liddle's syndrome is caused by mutations in the beta subunit of the epithelial sodium channel. The mutations result in inappropriate channel patency and increased distal sodium reabsorption. Both of these forms of inherited hypertension are low-renin forms of hypertension. Glucocorticoid-remediable aldosteronism resembles primary aldosteronism, whereas Liddle's syndrome resembles low-renin essential hypertension. An autosomal-dominant genetic form of hypertension has been described in northeastern Turkey. The hypertension cosegregates 100% with brachydactyly. This form resembles essential hypertension, because levels of renin, aldosterone, catecholamines and other regulators are normal. Furthermore, in contrast to glucocorticoid-remediable aldosteronism and Liddle's syndrome, the patients are not salt-sensitive.
Mechanisms of mineralcorticoid hypertension, renally induced salt-sensitive hypertension, and possibly essential hypertension, may be elucidated by studying exceptional families.
探讨罕见单基因形式高血压与原发性高血压诊断、发病机制及治疗的相关性。
已确定三种单基因形式的高血压，其遗传方式为简单常染色体显性性状。其中两种，即糖皮质激素可治性醛固酮增多症和利德尔综合征的遗传缺陷及病理生理学已得到详细阐明。正在研究与第二种表型短指共分离的第三种单基因高血压形式。
糖皮质激素可治性醛固酮增多症由嵌合基因的存在引起，该嵌合基因包含11-β-羟化酶基因的调控区和醛固酮合酶基因的结构部分。在此情况下，醛固酮合酶不仅在束状带表达，还受促肾上腺皮质激素调节。利德尔综合征由上皮钠通道β亚基的突变引起。这些突变导致通道异常开放和远端钠重吸收增加。这两种遗传性高血压均为低肾素型高血压。糖皮质激素可治性醛固酮增多症类似于原发性醛固酮增多症，而利德尔综合征类似于低肾素原发性高血压。在土耳其东北部描述了一种常染色体显性遗传形式的高血压。该高血压与短指100%共分离。这种形式类似于原发性高血压，因为肾素、醛固酮、儿茶酚胺和其他调节因子水平正常。此外，与糖皮质激素可治性醛固酮增多症和利德尔综合征不同，患者对盐不敏感。
通过研究特殊家系，可能阐明盐皮质激素性高血压、肾性盐敏感性高血压以及可能的原发性高血压的发病机制。
