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

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Abstract
The T594M allele of the epithelial sodium channel β-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.