Published Online
on January 23, 2006

A more recent version of this article appeared on March 1, 2006

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Submitted on August 31, 2005
Revised on September 27, 2005

Epithelial Sodium Channel Allele T594M Is Not Associated With Blood Pressure or Blood Pressure Response to Amiloride

John M. Hollier; Dan F. Martin; Darin M. Bell; Jia-Ling Li; Mike G. Chirachanchai; Dileep V. Menon; David Leonard; Xiaodong Wu; Richard S. Cooper; Colin McKenzie; Ronald G. Victor; and Richard J. Auchus^*

From the Donald W. Reynolds Cardiovascular Clinical Research Center (R.G.V., R.J.A.), Divisions of Hypertension (J.M.H., D.F.M., D.M.B., J.-L.L., M.G.C., D.V.M., D.L., R.G.V.) and Endocrinology (R.J.A.), Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Tex; Department of Preventative Medicine and Epidemiology (X.W., R.S.C.), Loyola University Stritch School of Medicine, Maywood, Ill; and University of the West Indies (C.M.), Kingston, Jamaica.

^* To whom correspondence should be addressed. E-mail: Richard.Auchus{at}UTSouthwestern.edu.

Abstract--The T594M allele of the epithelial sodium channel -subunit has been proposed as a gain-of-function mutation leading to salt-sensitive hypertension in blacks that is particularly responsive to the specific sodium channel antagonist amiloride. However, the positive associations derive from small convenience samples, and the amiloride challenge study lacked a control group. We determined whether the T594M allele was associated with hypertension and blood pressure (BP) response to amiloride in 2 well-characterized random population samples including 3137 Dallas County subjects and 1666 Jamaican blacks. In multivariate models, the T594M allele was not predictive of systolic BP (adjusted odds ratio for hypertension 1.1; 95% confidence interval, 0.7 to 1.8). Amiloride treatment did not lower the BP of 6 T594M heterozygotes significantly more than in 22 control subjects (P=0.8). We conclude that the T594M allele does not contribute significantly to BP in blacks and does not predict a significantly superior response to amiloride therapy.

Key words: hypertension, genetic • ion channels • sodium

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