Polymorphisms of the γ subunit of the epithelial Na+ channel in essential hypertension

    loading  Checking for direct PDF access through Ovid

Abstract

Objective

The γ subunit of the epithelial Na channel (γENaC) has been implicated in Liddle's syndrome. The objective of this study was to examine its status in essential hypertension.

Design and methods

The search for molecular variants was performed using the SSCP technique after determination of the intron–exon boundaries of the transcribed sequence. We found an additional 205 bp intron splitting the published exon 10 in two. The last exon of γENaC was tested with samples from a series of 245 normotensive patients and 453 hypertensive subjects (383 Caucasians, 70 Afro-Caribbeans), all probands of hypertensive families in the HYPERGENE data set. The search was extended to the other 11 transcribed exons in a subset of 65 patients with low-renin profile.

Results

Four neutral polymorphisms were detected, three in the third exon of the gene (T387C, T474C, C549T) and one in the last exon (C1990G). These four variants were found with similar frequencies in hypertensive and normotensive Caucasian subjects as well as in patients with low-renin profile. Hypertensive Caucasians and hypertensive subjects of African ancestry also had similar frequencies. Lastly, we found two rare mutations, one the insertion of a proline residue at position 594 of the mature protein (594insP), the other an Arg-to-His substitution at position 631 (R631H). Compared to wild-type (1.00 ± 0.42, n = 26), expression of the 594insP (1.10 ± 0.43, n = 26) and R631H (0.97 ± 0.43, n = 26) variants in Xenopus oocytes produced no significant increase in Na+ current.

Conclusions

Screening of the entire coding sequence of γENaC does not suggest that this subunit is frequently involved in essential hypertension.

Related Topics

    loading  Loading Related Articles