(Hypertension. 1996;28:478-482.)
© 1996 American Heart Association, Inc.
Articles |
Genetic Association of 11ß-Hydroxysteroid Dehydrogenase Type 2 (HSD11B2) Flanking Microsatellites With Essential Hypertension in Blacks
the Division of Nephrology, University of Alabama School of Medicine, Nephrology Research and Training Center, and Department of Veterans Affairs Medical Center, Birmingham, Ala (B.W., S.M.B., A.M., D.G.W.); Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, North Adelaide, South Australia (D.F.C.); and Departments of Microbiology, Medicine and the Immunogenetics/DNA Diagnostic Laboratory–University of Alabama Health Services Foundation, Birmingham (R.T.A.).
Correspondence to Bracie Watson, Jr, PhD, Division of Nephrology, Department of Medicine, Nephrology Research and Training Center, University of Alabama at Birmingham, Zeigler Research Building, 703 S 19th St, Birmingham, AL 35294-0007. E-mail bracie_watson.nephrology@nrtc.dom.uab.edu.
11ß-Hydroxysteroid dehydrogenase type 2 (11ß-HSD2) specifically modulates access of the mineralocorticoid aldosterone to the kidney mineralocorticoid type 1 receptors in a physiological environment in which there is a molar excess of cortisol. Cortisol and aldosterone have similar affinities for mineralocorticoid receptors. Mechanistically, 11ß-HSD2 converts cortisol to cortisone. The other known isoform, 11ß-HSD1, not only catalyzes the cortisol to cortisone reaction but also the reverse reaction, making it unlikely to play an important role in modulating the access of aldosterone to mineralocorticoid receptors. Mutations in the HSD11B2 gene (both exonic and intronic) have been demonstrated to cause reduced activity of this enzyme in the syndrome of apparent mineralocorticoid excess, a rare autosomal recessive disorder. We hypothesized that this locus is also involved in the etiology of essential hypertension. To test this locus and flanking chromosomal regions for allelic association and genetic linkage to essential hypertension, it is necessary to have informative genetic markers. To this end, we have refined the localization of 11ß-HSD2 to 16q22.1. We genotyped subjects using the nearest flanking microsatellites (D16S301 and D16S496). We conducted an association study using black subjects with hypertensive end-stage renal disease, black normotensive control subjects, and black and white individuals from the general population. We used 
2 analysis and Fisher's exact test to test for association with these candidate gene markers. No significant association was found between D16S301 and hypertension. However, a positive association with hypertension was found at the D16S496 microsatellite locus (2=6.98, df=1, P
.008). Our data suggest that HSD11B2 is associated with hypertension in our black subjects with hypertensive end-stage renal disease. The 16q22.1 chromosome region potentially harbors a candidate gene for essential hypertension. Confirmation of our findings in another independently ascertained group of hypertensive subjects will provide a basis for proceeding with sib-pair linkage analyses.
Key Words: hypertension, essential • hydroxysteroid dehydrogenase • genetics • hydrocortisone • aldosterone • blacks
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