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


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 gammaENaC 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 gammaENaC does not suggest that this subunit is frequently involved in essential hypertension.
Unité INSERM U36, Collège de France and Laboratoire de Génétique Moléculaire, Hôpital Broussais, Paris.
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Persu
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Coscoy
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Houot
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Corvol
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Barbry
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Jeunemaitre
D000818:Animals; D053503:Epithelial Sodium Channels; D005260:Female; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D011994:Recombinant Proteins; D015222:Sodium Channels / Q000235:genetics*; D014981:Xenopus
D053503:Epithelial Sodium Channels; D011994:Recombinant Proteins; D015222:Sodium Channels