Genetic association of 11 β-hydroxysteroid dehydrogenase type 2 flanking microsatellites with primary hypertension in African Americans

Academic Article


  • 11β-hydrojtysteroid dehydrogenase type 2 (HSD11B2) converts cortisol to cortisone, and permits aldosterone, to gain access to the mineralocorticoid receptors in a physiologic environment where there is a molar excess of cortisol. Recently, mutations in HSD11B2 have been found to cause a rare hypertensive disorder, apparent mineralocorticoid excess (AME). We hypothesized that mutations or polymorphisms in and/or flanking the HSD11B2 gene are genetically associated with susceptibility to development of other forms of hypertension. To test the hypothesis, we focused upon hypertension where the proband had hypertensive end-stage renal disease (H-ESRD). Subjects were members of a genelic subpopulation, African Americans, which as a group have a predominance of low-renin, saltsensitive hypertension and increased risk of progression to ESRD. After refining the genetic map location of this gene to chromosome I6q22.1, using a high resolution chromosome 16 mapping panel, we identified flanking microsatellites D16S301 and D16S496. Hypertensive subjects (n=73) and normotensive controls (n=67) were then genotyped using these microsatellites flanking the HSD11B2 gene. Chi-square analysis was used to test for association with candidate gene markers. No association was found between DI6S30I and hypertension. However, positive association with hypertension was found with the D16S496 microsatellite (aliele 10; x2 = 7 56, dfcl, p S 0.006). Our data suggest that HSD11B2 is associated with hypertension in our H-ESRD subjects and that the 16q22.1 region of chromosome 16 should be further assessed via genotype/clinical phenotype correlation and genotype evaluation of other candidate ioci in this region. Further, these data define a specific chromosomal region with known microsatellites and rich in candidate loci that can now be used in sibpair linkage analyses.
  • Published In

    Author List

  • Watson B; Bergman S; Myracle A; Callen DF; Acton RT; Warnock DC
  • Volume

  • 44
  • Issue

  • 3