The enzyme 11 beta-hydroxysteroid dehydrogenase type 2 (11BHSD2) converts cortisol to cortisone in the kidney, thereby protecting the mineralocorticoid receptor from the mineralocorticoid actions of cortisol. The syndrome of Apparent Mineralocorticoid Excess (AME), a rare monogenic form of early onset hypertension with autosomal recessive inheritance, is caused by homozygous or compound heterozygous loss of function mutations in the 11BHSD2 gene. Association has been reported between a microsatellite marker flanking the 11BHSD2 gene (D16S496) and primary hypertension. The aim of this study was to identify variants in the 11BHSD2 gene and to test if such variants or the D16S496 are associated with primary hypertension, in Swedes. To address this, the coding sequences of the 11BHSD2 gene was screened for mutations in 20 patients with primary hypertension with single strand conformation polymorphism and direct DNA sequencing techniques. A polymorphism was identified in exon 3; G534A (Glu178Glu). This polymorphism and the D16S496 microsatellite were tested for association with primary hypertension in a population consisting of 292 patients with primary hypertension and 263 normotensive control subjects. The frequency of G534G homozygotes was higher in patients with primary hypertension than in normotensive control subjects (92.8% vs 87.8%; P < 0.05). The allele frequencies of the D16S496 microsatellite did not differ between the two groups (chi(2) = 11.0, df = 10; P = 0.36). In conclusion, over-representation of individuals homozygous for the G534 allele in hypertensive patients compared with control subjects suggests that a mutation in linkage disequilibrium with the G534A polymorphism could increase susceptibility to primary hypertension. Journal of Human Hypertension (2000) 14, 819-823

中文翻译：

---

11β-羟类固醇脱氢酶2型基因变异与原发性高血压之间的关联。

2型11β-羟类固醇脱氢酶（11BHSD2）在肾中将皮质醇转化为可的松，从而保护盐皮质激素受体免受皮质醇的盐皮质激素作用。明显的盐皮质激素过量综合征（AME）是一种罕见的早发性高血压的单基因形式，具有常染色体隐性遗传，是由11BHSD2基因的纯合或复合杂合丧失功能突变引起的。据报道，侧翼为11BHSD2基因的微卫星标记（D16S496）与原发性高血压相关。这项研究的目的是在瑞典人中鉴定11BHSD2基因的变异体，并测试这些变异体或D16S496是否与原发性高血压相关。为了解决这个问题，通过单链构象多态性和直接DNA测序技术，筛选了20例原发性高血压患者的11BHSD2基因编码序列的突变。在外显子3中鉴定出多态性；G534A（Glu178Glu）。测试了这种多态性和D16S496微卫星与292名原发性高血压患者和263名血压正常对照者组成的人群中与原发性高血压的相关性。原发性高血压患者的G534G纯合子频率高于血压正常对照者（92.8％vs 87.8％； P <0.05）。两组之间D16S496微卫星的等位基因频率没有差异（chi（2）= 11.0，df = 10; P = 0.36）。结论，与对照组相比，高血压患者中G534等位基因纯合子个体的过度表达提示，具有G534A多态性的连锁不平衡突变可能增加原发性高血压的易感性。人类高血压杂志（2000）14，819-823