(Hypertension. 1999;34:631-637.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Genetic Variants in the Epithelial Sodium Channel in Relation to Aldosterone and Potassium Excretion and Risk for Hypertension
From the Department of Medicine, Indiana University School of Medicine (W.T.A., L.J.B., L.Z., J.F.R., M.A.W., C.G., J.H.P.), and the VA Medical Center (M.A.W., C.G., J.H.P.), Indianapolis, Ind; and the Department of Internal Medicine, University of Iowa College of Medicine (P.M.S.), Iowa City, Iowa.
Correspondence to J. Howard Pratt, MD, 541 Clinical Dr, Indianapolis, IN 46202-5111. E-mail johpratt{at}iupui.edu
Abstract—Renin and
aldosterone secretion is often lower in blacks than in
whites, characteristics that resemble a milder form of Liddle syndrome
in which a mutation in the amiloride-sensitive epithelial sodium
channel (ENaC) of the kidney results in enhanced resorption of sodium.
In the present study, we looked for evidence that the intrinsic
level of ENaC activity is indeed higher in blacks than in whites. In
overnight urine samples collected from young people (249 white and 181
black subjects, mean age 13.4 years), the urinary
aldosterone/potassium ratio, which is typically very low in
Liddle syndrome, was lower in blacks than in whites: 0.421±0.024
(mean±SE) versus 0.582±0.016 nmol/mmol (P<0.0001). In
addition, all but 1 of 5 molecular variants in ENaC were much more
common in blacks than in whites. G442V in the ß-subunit, present
in 16% of the blacks and in only 1 white, was associated with
parameters reflective of a greater Na retention and
potentially a higher ENaC activity: a lower plasma
aldosterone concentration (P=0.070), a lower
urinary aldosterone excretion rate
(P=0.052), a higher potassium excretion rate
(P=0.048), and a lower urinary
aldosterone/potassium ratio (P=0.027). In a
second cohort consisting of 126 black and 161 white normotensive
subjects and 232 black and 188 white hypertensive subjects, ßG442V
did not show a significant association with hypertension
(P=0.089). On the other hand, a variant that was twice
as common in whites, 
T663A, was associated with being normotensive
both in blacks (P=0.018) and in whites
(P=0.034). Expression of either ßG442V or T663A in
Xenopus oocytes did not result in a change in basal Na
current, consistent with the variants being in linkage
disequilibrium with alleles at active loci. In conclusion, several
lines of evidence are presented to suggest that ENaC activity
is higher in blacks than in whites, which could contribute to racial
differences in Na retention and the risk for hypertension.
Key Words: sodium channels • aldosterone • potassium • hypertension, sodium-dependent • race
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