人原发性高血压中2型11β-羟基类固醇脱氢酶基因（HSD11B2）的分析

Analysis of the 11beta-hydroxysteroid dehydrogenase type 2 gene (HSD11B2) in human essential hypertension.

作者信息

Mariniello Barbara, Ronconi Vanessa, Sardu Cipriana, Pagliericcio Antonella, Galletti Ferruccio, Strazzullo Pasquale, Palermo Mario, Boscaro Marco, Stewart Paul M, Mantero Franco, Giacchetti Gilberta

机构信息

Division of Endocrinology, Department of Internal Medicine, Università Politecnica delle Marche, Umberto I Hospital, Ancona, Italy.

出版信息

Am J Hypertens. 2005 Aug;18(8):1091-8. doi: 10.1016/j.amjhyper.2005.02.020.

DOI:10.1016/j.amjhyper.2005.02.020

PMID:16109323

Abstract

BACKGROUND

The HSD11B2 gene, encoding the kidney isoenzyme 11beta-hydroxysteroid dehydrogenase, is a candidate for essential hypertension. We previously showed that the frequency of shorter alleles of a CA repeat polymorphism in the first intron of 11beta-HSD2 gene was significantly higher among salt-sensitive than salt-resistant individuals with hypertension. The aim of the study was to analyze the HSD11B2 gene to assess whether some of its variants might be involved in hypertension.

METHODS

Exons 2, 3, 4, and 5 were screened by polymerase chain reaction-single-strand conformation polymorphism analysis in 292 hypertensive patients and 163 control subjects. The samples with variant electrophoretic patterns at single-strand conformation polymorphism were re-analyzed using an automated DNA sequencer. A case-control study was then performed by comparing genotype frequencies in hypertensive and normotensive subjects.

RESULTS

Analysis of the HSD11B2 showed that in hypertensive patients there is a higher prevalence of two associated polymorphisms, Thr156/Thr(C468A) in exon 2 (ex2) and Glu178/Glu(G534A) in exon 3 (ex3), than in normotensive subjects (9% v 2.4%). This association did not correlate with salt sensitivity. C468A alone correlates significantly with hypertension (9%) and was identified only in 3% of control subjects (P < .05), whereas G534A was identified also in about 7% of normotensive subjects. The urinary free cortisol/urinary free cortisone ratio (UFF/UFE) was significantly higher in hypertensive patients compared with control subjects (P < .01).

CONCLUSIONS

Two different polymorphisms of the HSD11B2 gene were observed. The association of both polymorphisms was significantly higher in hypertensive subjects than in control subjects. Its role should be further investigated, but it could be related to other mutations in the promoter region of HSD11B2 or to the modulation of 11beta-HSD2 mRNA processing in hypertensive subjects.

摘要

背景

编码肾脏同工酶11β - 羟基类固醇脱氢酶的HSD11B2基因是原发性高血压的一个候选基因。我们之前发现，在高血压患者中，盐敏感者11β - HSD2基因第一内含子中CA重复多态性的短等位基因频率显著高于盐抵抗者。本研究的目的是分析HSD11B2基因，以评估其某些变异是否可能与高血压有关。

方法

通过聚合酶链反应 - 单链构象多态性分析对292例高血压患者和163例对照者的第2、3、4和5外显子进行筛查。对单链构象多态性电泳模式有变异的样本使用自动DNA测序仪重新分析。然后通过比较高血压患者和血压正常者的基因型频率进行病例对照研究。

结果

HSD11B2分析显示，高血压患者中两种相关多态性的患病率高于血压正常者，即第2外显子（ex2）中的Thr156/Thr（C468A）和第3外显子（ex3）中的Glu178/Glu（G534A）（9%对2.4%）。这种关联与盐敏感性无关。单独的C468A与高血压显著相关（9%），仅在3%的对照者中发现（P <.05），而G534A在约7%的血压正常者中也有发现。与对照者相比，高血压患者的尿游离皮质醇/尿游离可的松比值（UFF/UFE）显著更高（P <.01）。