Genetic Analysis of the β Subunit of the Epithelial Na + Channel in Essential Hypertension
- 1 July 1998
- journal article
- other
- Published by Wolters Kluwer Health in Hypertension
- Vol. 32 (1) , 129-137
- https://doi.org/10.1161/01.hyp.32.1.129
Abstract
—Mutations of the last exon of the β subunit of the amiloride-sensitive epithelial Na + channel (βENaC) 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 βENaC could be implicated in essential hypertension. After determination of the βENaC 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 22 Na + 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 βENaC gene in essential hypertension.Keywords
This publication has 21 references indexed in Scilit:
- A novel spice–site mutation in the γ subunit of the epithelial sodium channel gene in three pseudohypoaldosteronism type 1 familiesNature Genetics, 1996
- Liddle disease caused by a missense mutation of beta subunit of the epithelial sodium channel gene.Journal of Clinical Investigation, 1996
- Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1Nature Genetics, 1996
- A de novo missense mutation of the beta subunit of the epithelial sodium channel causes hypertension and Liddle syndrome, identifying a proline-rich segment critical for regulation of channel activity.Proceedings of the National Academy of Sciences, 1995
- Hypertension caused by a truncated epithelial sodium channel γ subunit: genetic heterogeneity of Liddle syndromeNature Genetics, 1995
- Cloning, Chromosomal Localization, and Physical Linkage of the β and γ Subunits (SCNN1B and SCNN1G) of the Human Epithelial Amiloride-Sensitive Sodium ChannelGenomics, 1995
- Cloning and expression of the beta- and gamma-subunits of the human epithelial sodium channelAmerican Journal of Physiology-Cell Physiology, 1995
- Liddle's syndrome: Heritable human hypertension caused by mutations in the β subunit of the epithelial sodium channelCell, 1994
- Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reactionGenomics, 1989
- DNA sequencing with chain-terminating inhibitorsProceedings of the National Academy of Sciences, 1977