Association between a variant in the 11 beta-hydroxysteroid dehydrogenase type 2 gene and primary hypertension

The enzyme 11 beta -hydroxysteroid dehydrogenase type 2 (11BHSD2) converts cortisol to cortisone in the kidney, thereby protecting the mineralocortico id receptor from the mineralocorticoid actions of cortisol. The syndrome of Apparent Mineralocorticoid Excess (AME), a rare monogenic form of early on set hypertension with autosomal recessive inheritance, is caused by homozyg ous or compound heterozygous loss of function mutations in the 11BHSD2 gene . Association has been reported between a microsatellite marker flanking th e 11BHSD2 gene (D16S496) and primary hypertension. The aim of this study wa s 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 po lymorphism and direct DNA sequencing techniques. A poly-morphism was identi fied in exon 3; G534A (Glu178Glu). This polymorphism and the D16S496 micros atellite were tested for association with primary hypertension in a populat ion consisting of 292 patients with primary hypertension and 263 normotensi ve control subjects. The frequency of G534G homozygotes was higher in patie nts with primary hypertension than in normotensive control subjects (92.8% vs 87.8%; P < 0.05). The allele frequencies of the D16S496 microsatellite d id not differ between the two groups (<chi>(2) = 11.01 df = 10; P = 0.36), In conclusion, over-representation of individuals homozygous for the G534 a llele in hypertensive patients compared with control subjects suggests that a mutation in linkage disequilibrium with the G534A polymorphism could inc rease susceptibility to primary hypertension.