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Polymorphisms in 5′UTR of ENaC α, β and γgenes in Dahl and Wistar rats
Author(s) -
Shehata Marlene Fouad,
Leenen Frans HH,
Tesson Frederique
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a310-d
Subject(s) - epithelial sodium channel , single nucleotide polymorphism , untranslated region , gene , three prime untranslated region , biology , genetics , promoter , microbiology and biotechnology , medicine , endocrinology , gene expression , messenger rna , genotype , sodium , chemistry , organic chemistry
The activity of the epithelial sodium channel (ENaC) in the kidney is elevated in salt sensitive (SS) versus salt resistant (SR) Dahl rats. Blockade of ENaC in the brain by benzamil prevents the increase in BP in SS Dahl rats on high salt diet. Previously, we did a comprehensive screening of the complete coding regions of ENaC α, β and γ genes and no differences were identified in SS versus SR Dahl rats. In the presentstudy, we assessed whether the promotor regions of ENaC genes might harbor genetic variation(s) that enhance ENaC expression and contribute to salt sensitivity in Dahl SS, but not SR rats. Methods Screening 5′UTR of ENaC genes in Dahl SS, SR and control Wistar rats by Denaturing High Performance Liquid Chromatography (DHPLC) and automatic sequencing. Results Screening 2.2, 1.5, and 2.2 kb of 5′UTR of ENaCα, β and γ respectively showed no differences between Dahl SS and SR rats. A total of 18 SNPs; 4 SNPs in ENaCα 5′UTR, 2 in ENaCβ5′UTR, and 12 in ENaCγ 5′UTR were identified in Dahl SS and SR rats. 4 of these 18 SNPs were previously identified in the genome database of Brown Norway rats. The remaining 14 SNPs are novel polymorphisms. Of these 14 SNPs, 13 were also identified in Wistar rats. None of the identified SNPs in the 5′UTR of ENaC genes were located within the previously reported regulatory element DNA consensus sequences. Conclusions The first comprehensive screening of ENaC genes 5′UTR did not reveal any differences between SS and SR. Therefore, we could not link differences in activity of ENaC in SS versus SR to differences in ENaC 5′UTR sequences. The identified variations in ENaC genes 5′UTR on their own can not explain salt‐sensitive hypertension in Dahl SS rats.