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From Unité INSERM U36, Collège de France and Laboratoire de
Génétique Moléculaire, Hôpital Broussais, Paris
(A.P., A.-M.H., P.C., X.J.); and Institut de Pharmacologie Moléculaire
et Cellulaire, CNRS, UPR 411, Sophia Antipolis (P.B., F.B., R.M., M.L.),
France.
Correspondence to X. Jeunemaitre, INSERM U36, Collège de France, 3 rue d'Ulm, 75005 Paris, France. E-mail jeunemaitre{at}hbroussais.fr
Abstract—Mutations of the last exon
of the ß subunit of the amiloride-sensitive epithelial
Na+ channel (ßENaC) can lead to Liddle's syndrome, a
rare monogenic form of hypertension. The objective of this study was to
test whether more subtle changes of ßENaC could be implicated in
essential hypertension. After determination of the ßENaC coding gene
organization (12 exons spanning 23.5 kb), a systematic screening of the
last exon of the gene was performed in 525 subjects (475 whites, 50
Afro-Caribbeans), all probands of hypertensive families. This search
was extended to the remaining 11 exons in a subset of 101 probands with
low-renin hypertension. Seven amino acid changes were detected: G589S,
T594M, R597H, R624C, E632G (last exon), G442V, and V434M (exon 8).
These genetic variants were more frequent in subjects of African origin
(44%) than in whites (1%). The functional properties of the variants
were analyzed in Xenopus oocytes by two
independent techniques, ie, electrophysiology and
22Na+ uptake. Small but not significant
differences were observed between the variants and wild type. The
clinical evaluation of the family bearing the G589S variant, which
provided the highest relative ENaC activity, did not show a
cosegregation between the mutation and hypertension. The present
study illustrates the difficulty in establishing a relation of
causality between a susceptibility gene and hypertension. Furthermore,
it does not favor a substantial role of the ßENaC gene in
essential hypertension.
© 1998 American Heart Association, Inc.
Scientific Contributions
Genetic Analysis of the ß Subunit of the Epithelial Na+ Channel in Essential Hypertension
Key Words: sodium channels • genetics • polymorphism, single-stranded conformational • oocytes • hypertension, essential
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