Role of HSD11B2 polymorphisms in essential hypertension and the diuretic response to thiazides.

Abstract:

BACKGROUND:The renal 11beta-hydroxysteroid dehydrogenase type 2 (11beta HSD2) enzyme inactivates 11-hydroxy steroids in the kidney, thereby protecting the nonselective mineralocorticoid (MR) receptor from occupation by glucocorticoids. Loss-of-function mutations in the gene encoding 11beta HSD2 (HSD11B2) result in overstimulation of the MR and cause salt-sensitive hypertension. METHODS:We have investigated the role of HSD11B2 in hypertension in 377 genetically homogeneous essential hypertensives from North Sardinia. RESULTS:Thirty of these patients displayed increased urinary cortisol metabolite ratios (greater than or equal to 2) (tetrahydrocortisol [THF]+allotetrahydrocortisol [aTHF]/tetrahydrocortisone [THE]) reflecting a mild reduction in 11beta HSD2 activity. No mutations in HSD11B2 were detected in these patients. All 377 patients were genotyped for a CA repeat microsatellite in intron 1 of HSD11B2 and a G534A polymorphism in exon 3 of HSD11B2. CA repeat length was associated with the (THF+aTHF)/THE ratio, which in turn was significantly related to PRA levels. No associations were found between the G354A polymorphism and the other parameters. There were no differences in blood pressure (BP) levels between HSD11B2 genotypes, but in a subgroup of 91 patients that underwent diuretic therapy, CA repeat length was strongly associated with the BP response to hydrochlorothiazide. CONCLUSION:This study highlights the role of this HSD11B2 polymorphism in sodium handling and is consistent with a role in the BP response to thiazide diuretics.

journal_name

Kidney Int

journal_title

Kidney international

authors

Williams TA,Mulatero P,Filigheddu F,Troffa C,Milan A,Argiolas G,Parpaglia PP,Veglio F,Glorioso N

doi

10.1111/j.1523-1755.2005.67119.x

subject

Has Abstract

pub_date

2005-02-01 00:00:00

pages

631-7

issue

2

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(15)50497-3

journal_volume

67

pub_type

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