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

Objective The gamma subunit of the epithelial Na channel (gamma ENaC) has b een implicated in Liddle's syndrome. The objective of this study was to exa mine its status in essential hypertension. Design and methods The search for molecular variants was performed using th e SSCP technique after determination of the intron-exon boundaries of the t ranscribed sequence. We found an additional 205 bp intron splitting the pub lished exon 10 in two. The last exon of gamma ENaC was tested with samples from a series of 245 normotensive patients and 453 hypertensive subjects (3 83 Caucasians, 70 Afro-Caribbeans), ail probands of hypertensive families i n the HYPERGENE data set. The search was extended to the other 11 transcrib ed exons in a subset of 65 patients with low-renin profile. Results Four neutral polymorphisms were detected, three in the third exon o f the gene (T387C, T474C, C549T) and one in the last exon (C1990G). These f our variants were found with similar frequencies in hypertensive and normot ensive Caucasian subjects as well as in patients with low-renin profile. Hy pertensive Caucasians and hypertensive subjects of African ancestry also ha d similar frequencies. Lastly, we found two rare mutations, one the inserti on of a proline residue at position 594 of the mature protein (594insP), th e other an Arg-to-His substitution at position 631 (R631H). Compared to wil d-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 produc ed no significant increase in Na+ current. Conclusions Screening of the entire coding sequence of gamma ENaC does not suggest that this subunit is frequently involved in essential hypertension. J Hypertens 1999, 17:639-645 (C) Lippincott Williams & Wilkins.