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A novel ‐1364 A/C Promotor Polymorphism of the Aquaporin 5 Gen Influences Aquaporin 5 Expression
Author(s) -
Adamzik Michael,
Frey Ulrich,
Bitzer Kathrin,
Jakob Heinz,
Baba Hideo,
Schmieder Roland,
Heusch Gerd,
Peters Jürgen,
Siffert Winfried
Publication year - 2007
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.21.6.a1413-a
Subject(s) - promoter , biology , snp , phenotype , homeostasis , microbiology and biotechnology , gene , allele , gene expression , aquaporin , genetics , gene isoform , single nucleotide polymorphism , genotype
Objectives: We have systematically sequenced the human AQP5 promoter to detect novel sequence variants, which could have an effect upon AQP5 expression and might, thereby, contribute to phenotypic variability of water homeostasis systems. Methods and Results: Sequencing of the whole promoter revealed one novel polymorphism at position ‐1364. Substitution of C for A at positions −1364 was associated with increased binding of transcriptions factors (tested with EMSA), and reduced transcriptional activation of the AQP5 gene in response to cAMP, as well as to serum (tested with reporter assay constructs in HELA cells). Furthermore, the C allele showed decreased mRNA and protein expression validated via realtime PCR and Western blot analysis. Phenotypic associations were tested with the renin‐angiotensin‐ aldosterone system (RAAS) in 103 young (26 ± 3 yr) healthy male subjects under high salt diet. Increased AQP5 expression was associated with an inadequate suppression of the RAAS in response to a high salt diet. Conclusion: This study is the first description of a novel gain of function SNP in the AQP5 promoter. This SNP influences AQP5 expression in humans and might, thereby, contribute to phenotypic variability regarding regulation of water and salt homeostasis.