Takeda Y
Second Department of Internal Medicine, School of Medicine, Kanazawa University, Japan.
Hypertens Res. 2001 Sep;24(5):469-74. doi: 10.1291/hypres.24.469.
The syndrome of primary aldosteronism is characterized by hypertension with excessive production of aldosterone, potassium loss, and suppression of the renin-angiotensin system. The most common clinical subtypes of primary aldosteronism are aldosterone-producing adrenocortical adenoma (APA) and bilateral adrenal cortical hyperplasia (idiopathic hyperaldosteronism, or IHA). It has been reported that renin suppression and aldosterone levels are lower and hypokalemia milder in patients with IHA than in patients with APA. In the present study, we investigated the genetic analysis of aldosterone synthase gene, CYP11B2 in patients with primary aldosteronism and review the recent studies. The chimeric CYP11B1/CYP11B2 gene, which is a candidate gene for glucocorticoid-remediable hyperaldosteronism, was not found in either the DNA from aldosteronoma or in the genomic DNA from patients with APA or IHA. Mutations in the CYP21 or CYP11B1 gene were not present in patients with APA. No mutations in the coding region of the CYP11B2 gene were found in patients with IHA or APA. The level of CYP11B2 messenger RNA (mRNA) was much higher in the aldosteronoma portion than in nonadenomatous portion. The overexpression of CYP11B2 mRNA seen in the mononuclear leukocytes of patients with IHA suggests that unidentified aldosterone-stimulating factors or abnormalities of the CYP11B2 promoter region may cause the overproduction of aldosterone characteristic of IHA. The variants of the CYP11B2 gene may also contribute to dysregulation of aldosterone synthesis and lead to susceptibility to IHA.
原发性醛固酮增多症的综合征特征为高血压伴醛固酮分泌过多、钾丢失以及肾素 - 血管紧张素系统受抑制。原发性醛固酮增多症最常见的临床亚型是醛固酮分泌性肾上腺皮质腺瘤（APA）和双侧肾上腺皮质增生（特发性醛固酮增多症，或IHA）。据报道，IHA患者的肾素抑制和醛固酮水平低于APA患者，低钾血症也较轻。在本研究中，我们对原发性醛固酮增多症患者的醛固酮合成酶基因CYP11B2进行了基因分析，并回顾了近期的研究。在醛固酮瘤的DNA或APA或IHA患者的基因组DNA中均未发现嵌合型CYP11B1/CYP11B2基因，而该基因是糖皮质激素可治性醛固酮增多症的候选基因。APA患者未出现CYP21或CYP11B1基因突变。IHA或APA患者的CYP11B2基因编码区未发现突变。醛固酮瘤部分的CYP11B2信使核糖核酸（mRNA）水平远高于非腺瘤部分。IHA患者单核细胞中CYP11B2 mRNA的过表达表明，未明的醛固酮刺激因子或CYP11B2启动子区域异常可能导致IHA特有的醛固酮过度分泌。CYP11B2基因的变异也可能导致醛固酮合成失调，并导致对IHA的易感性。
