Departamento de Endocrinología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
Am J Hypertens. 2012 May;25(5):597-603. doi: 10.1038/ajh.2011.263. Epub 2012 Jan 26.
11β-hydroxysteroid dehydrogenase type 2 enzyme (11β-HSD2) inactivates cortisol (F) to cortisone (E); its impairment is associated with hypertension. We reported that 15.7% of the Chilean essential hypertensives possessed a high F/E ratio suggesting a partial deficit in 11β-HSD2 activity. It has been reported that the G534A(Glu178/Glu) polymorphism in the HSD11B2 gene is associated with hypertension. Investigate the frequency of the G534A polymorphism and its correlation with the glucocorticoid profile in Chilean essential hypertensive and normotensive subjects.
Essential hypertensive outpatients (n = 232) and normotensive subjects (n = 74) were recruited. A change in the AluI restriction enzyme digest pattern, caused by the presence of the G534A polymorphism, was utilized to screen DNA isolated from leukocytes within the cohort before confirmation by sequencing. Plasma renin activity (PRA), serum aldosterone, F, and E were measured by radioimmunoassay. Urinary tetrahydrocortisol (THF), 5α-tetrahydrocortisol (5α-THF), and tetrahydrocortisone (THE) were measured by gas chromatography-mass spectrometry.
G534A polymorphism frequency was similar between hypertensive patients (19 of 232; 8.2%) and normotensive subjects (7 of 74; 9.5%). When categorized by presence or absence of the G534A polymorphism, no significant differences in the serum F/E ratio or other measured biochemical variables were detected. Despite a previous report that the G534A polymorphism is associated with a neighboring C468A (Thr156/Thr) polymorphism, analysis within our cohort showed that only one patient in each group presented with this double polymorphism.
We report the frequency of the G534A polymorphism in the Spanish-Amerindian population. No correlation was detected between this polymorphism and the presence of hypertension and biochemical parameters in this Chilean cohort.
11β-羟类固醇脱氢酶 2 型酶（11β-HSD2）可使皮质醇（F）失活为皮质酮（E）；其功能障碍与高血压有关。我们曾报道，15.7%的智利原发性高血压患者存在高 F/E 比值，提示 11β-HSD2 活性部分缺乏。有报道称，HSD11B2 基因中的 G534A（Glu178/Glu）多态性与高血压有关。本研究旨在调查智利原发性高血压和血压正常受试者中 G534A 多态性的频率及其与糖皮质激素谱的相关性。
招募了 232 名原发性高血压门诊患者和 74 名血压正常受试者。利用 AluI 内切酶消化模式的变化，即存在 G534A 多态性，对该队列中的白细胞 DNA 进行筛选，然后进行测序确认。通过放射免疫测定法测量血浆肾素活性（PRA）、血清醛固酮、F 和 E。通过气相色谱-质谱法测量尿四氢皮质醇（THF）、5α-四氢皮质醇（5α-THF）和四氢皮质酮（THE）。
高血压患者（232 例中的 19 例；8.2%）和血压正常受试者（74 例中的 7 例；9.5%）的 G534A 多态性频率相似。按是否存在 G534A 多态性分类，血清 F/E 比值或其他测量的生化变量无显著差异。尽管之前有报道称 G534A 多态性与邻近的 C468A（Thr156/Thr）多态性有关，但在我们的队列中分析显示，每组只有一名患者存在这种双重多态性。
我们报告了西班牙裔-美洲印第安人人群中 G534A 多态性的频率。在智利队列中，该多态性与高血压的发生及生化参数无相关性。
